View source for Medicine:COVID-19

{{Short description|Contagious disease caused by SARS-CoV-2}}
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{{EngvarB|date=April 2023}}
{{Infobox medical condition
| name          = Coronavirus disease 2019<br />(COVID-19)
| synonyms      = COVID, (the) coronavirus
| pronounce     = {{ubl|{{IPAc-en|k|ə|ˈ|r|oʊ|n|ə|v|aɪ|r|ə|s}}|{{IPAc-en|ˌ|k|oʊ|v|ᵻ|d|n|aɪ|n|ˈ|t|iː|n|,_|ˌ|k|ɒ|v|ᵻ|d|-}}<ref>{{cite OED |Covid-19 |id=88575495 |date=April 2020 |access-date=15 April 2020}}</ref>}}
| image         = Fphar-11-00937-g001.jpg
| image_size    = 250px
| caption       = {{longitem|Transmission and life-cycle of [[Biology:SARS-CoV-2|SARS-CoV-2]], which causes COVID-19}}
| specialty     = [[Medicine:Infectious disease (medical specialty)|Infectious disease]]
| symptoms      = Fever, cough, fatigue, shortness of breath, vomiting, loss of taste or smell; some cases asymptomatic<ref name="CDC2020Sym"><!-- KEEP THIS NAMED REFERENCE -->{{#invoke:Cite web||url=https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html |title=Symptoms of Coronavirus |date=13 May 2020|website=U.S. Centers for Disease Control and Prevention (CDC) |url-status=live|archive-url=https://web.archive.org/web/20200617081119/https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html|archive-date=17 June 2020|access-date=18 June 2020}}</ref><ref name="WHO2020QA">{{#invoke:Cite web||url=https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/q-a-coronaviruses |title=Q&A on coronaviruses (COVID-19) |date=17 April 2020 |publisher=[[Organization:World Health Organization|World Health Organization]] (WHO) |archive-url=https://web.archive.org/web/20200514224315/https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/q-a-coronaviruses |archive-date=14 May 2020 |url-status=live |access-date=14 May 2020}}</ref>
| complications = [[Medicine:Pneumonia|Pneumonia]], [[Medicine:Sepsis|sepsis]], [[Medicine:Acute respiratory distress syndrome|ARDS]], [[Medicine:Kidney failure|kidney failure]], [[Medicine:Respiratory failure|respiratory failure]], [[Medicine:Pulmonary fibrosis|pulmonary fibrosis]], [[Medicine:Cytokine release syndrome|CKS]], MIS-C, long COVID
| onset         = 2–14 days (typically 5) <br> after infection
| duration      = 5 days to chronic
| types         =
| cause         = [[Biology:SARS-CoV-2|SARS-CoV-2]]
| risks         =
| diagnosis     = [[Biology:Reverse transcription polymerase chain reaction|RT{{nbhyph}}PCR testing]], [[CT scan]], [[Biology:Rapid antigen test|rapid antigen test]]
| differential  =
| prevention    = [[Medicine:COVID-19 vaccine|Vaccination]], face coverings, [[Medicine:Quarantine|quarantine]], [[Medicine:Social distancing|social distancing]], ventilation, hand washing
| treatment     = Symptomatic and supportive
| medication    =
| prognosis     =
| frequency     = {{COVID-19 data/Text|XW|cases}} confirmed cases
| deaths        = {{ubl|{{COVID-19 data/Text|XW|deaths}} (reported)|18.2–33.5&nbsp;million<ref>{{#invoke:cite news ||title=The pandemic's true death toll |newspaper=The Economist |url=https://www.economist.com/graphic-detail/coronavirus-excess-deaths-estimates |orig-date=2 November 2021 |date=28 August 2023 |access-date=28 August 2023}}</ref> (estimated)}}
| alt           =
}}
'''Coronavirus disease 2019''' ('''COVID-19''') is a [[Philosophy:Contagious disease|contagious disease]] caused by the virus [[Biology:SARS-CoV-2|SARS-CoV-2]]. The first known case was identified in Wuhan,<!---Wuhan is the capital of Hubei---> China, in December 2019.<ref name="WSJ-20210226">{{#invoke:cite news || vauthors = Page J, Hinshaw D, McKay B |title=In Hunt for Covid-19 Origin, Patient Zero Points to Second Wuhan Market – The man with the first confirmed infection of the new coronavirus told the WHO team that his parents had shopped there |url=https://www.wsj.com/articles/in-hunt-for-covid-19-origin-patient-zero-points-to-second-wuhan-market-11614335404 |date=26 February 2021 |work={{wipe|The Wall Street Journal}} |access-date=27 February 2021 }}</ref> The disease quickly spread worldwide, resulting in the COVID-19 pandemic.

The symptoms of COVID‑19 are variable but often include fever,<ref>{{#invoke:cite journal ||vauthors=Islam MA |date=April 2021 |title=Prevalence and characteristics of fever in adult and paediatric patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of 17515 patients |journal=PLOS ONE |volume=16 |issue=4 |pages=e0249788 |bibcode=2021PLoSO..1649788I |doi=10.1371/journal.pone.0249788 |pmc=8023501 |pmid=33822812 |doi-access=free |title-link=doi}}</ref> cough, headache,<ref>{{#invoke:cite journal ||vauthors=Islam MA |date=November 2020 |title=Prevalence of Headache in Patients With Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of 14,275 Patients |journal=Frontiers in Neurology |volume=11 |page=562634 |doi=10.3389/fneur.2020.562634 |pmc=7728918 |pmid=33329305 |doi-access=free |title-link=doi}}</ref> fatigue, breathing difficulties, [[Medicine:Anosmia|loss of smell]], and loss of taste.<ref>{{#invoke:cite journal ||vauthors=Saniasiaya J, Islam MA |date=April 2021 |title=Prevalence of Olfactory Dysfunction in Coronavirus Disease 2019 (COVID-19): A Meta-analysis of 27,492 Patients |journal=The Laryngoscope |volume=131 |issue=4 |pages=865–878 |doi=10.1002/lary.29286 |issn=0023-852X |pmc=7753439 |pmid=33219539}}</ref><ref>{{#invoke:cite journal ||vauthors=Saniasiaya J, Islam MA |date=November 2020 |title=Prevalence and Characteristics of Taste Disorders in Cases of COVID-19: A Meta-analysis of 29,349 Patients |journal=Otolaryngology–Head and Neck Surgery |volume=165 |issue=1 |pages=33–42 |doi=10.1177/0194599820981018 |pmid=33320033 |s2cid=229174644|url=http://pure-oai.bham.ac.uk/ws/files/185167818/COVID_19_and_taste_disorders_V1.pdf }}</ref><ref>{{#invoke:cite journal ||vauthors=Agyeman AA, Chin KL, Landersdorfer CB, Liew D, Ofori-Asenso R |date=August 2020 |title=Smell and Taste Dysfunction in Patients With COVID-19: A Systematic Review and Meta-analysis |journal=Mayo Clin. Proc. |volume=95 |issue=8 |pages=1621–1631 |doi=10.1016/j.mayocp.2020.05.030 |pmc=7275152 |pmid=32753137}}</ref> Symptoms may begin one to fourteen days [[Medicine:Incubation period|after exposure]] to the virus. At least a third of people who are infected [[Medicine:Asymptomatic|do not develop noticeable symptoms]].<ref>{{#invoke:cite journal ||vauthors=Wang B, Andraweera P, Elliott S, Mohammed H, Lassi Z, Twigger A, Borgas C, Gunasekera S, Ladhani S, Marshall HS |title=Asymptomatic SARS-CoV-2 Infection by Age: A Global Systematic Review and Meta-analysis |journal=The Pediatric Infectious Disease Journal |date=March 2023 |volume=42 |issue=3 |pages=232–239 |doi=10.1097/INF.0000000000003791 |pmid=36730054 |pmc=9935239 |url=https://journals.lww.com/pidj/fulltext/2023/03000/asymptomatic_sars_cov_2_infection_by_age__a_global.12.aspx |access-date=15 November 2023}}</ref><ref>{{#invoke:cite journal ||vauthors=Oran DP, Topol EJ |date=January 2021 |title=The Proportion of SARS-CoV-2 Infections That Are Asymptomatic: A Systematic Review |journal=Annals of Internal Medicine |volume=174 |issue=5 |pages=M20-6976 |doi=10.7326/M20-6976 |pmc=7839426 |pmid=33481642}}</ref> Of those who develop symptoms noticeable enough to be classified as patients, most (81%) develop mild to moderate symptoms (up to mild [[Medicine:Pneumonia|pneumonia]]), while 14% develop severe symptoms (dyspnea, [[Medicine:Hypoxia (medical)|hypoxia]], or more than 50% lung involvement on imaging), and 5% develop critical symptoms ([[Medicine:Respiratory failure|respiratory failure]], [[Medicine:Shock (circulatory)|shock]], or multiorgan dysfunction).<ref name="CDC Interim Guidance">{{#invoke:cite web||date=6 April 2020|title=Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19)|url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html|url-status=live|archive-url=https://web.archive.org/web/20200302201644/https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html|archive-date=2 March 2020|access-date=19 April 2020|website=U.S. Centers for Disease Control and Prevention (CDC)}}</ref> Older people are at a higher risk of developing severe symptoms. Some people continue to experience a range of effects (long COVID) for months or years after infection, and damage to organs has been observed.<ref name="davis" /> Multi-year studies are underway to further investigate the long-term effects of the disease.<ref name="CDC-2020">{{#invoke:Cite web||last=CDC|date=11 February 2020|title=Post-COVID Conditions|url=https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html|access-date=12 July 2021|website=U.S. Centers for Disease Control and Prevention (CDC)}}</ref>

COVID‑19 transmits when infectious particles are breathed in or come into contact with the eyes, nose, or mouth. The risk is highest when people are in close proximity, but small airborne particles containing the virus can remain suspended in the air and travel over longer distances, particularly indoors. Transmission can also occur when people touch their eyes, nose or mouth after touching surfaces or objects that have been contaminated by the virus. People remain contagious for up to 20 days and can spread the virus even if they do not develop symptoms.<ref>{{#invoke:cite web ||title=Coronavirus disease (COVID-19): How is it transmitted? |url=https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-covid-19-how-is-it-transmitted |access-date=13 April 2023 |website=www.who.int |language=en}}</ref>

Testing methods for COVID-19 to detect the virus's [[Biology:Nucleic acid|nucleic acid]] include [[Biology:Reverse transcription polymerase chain reaction|real-time reverse transcription polymerase chain reaction]] (RT{{nbhyph}}PCR),<ref name="CDC testing">{{#invoke:cite web||title=Overview of Testing for SARS-CoV-2, the virus that causes COVID-19|publisher=U.S. Centers for Disease Control and Prevention (CDC)|date=11 February 2020|url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/testing-overview.html|access-date=31 July 2022}}</ref><ref name="CDC NAATs">{{#invoke:cite web||title=Nucleic Acid Amplification Tests (NAATs)|publisher=U.S. Centers for Disease Control and Prevention (CDC)|date=11 February 2020|url=https://www.cdc.gov/coronavirus/2019-ncov/lab/naats.html|access-date=31 July 2022}}</ref> [[Biology:Transcription-mediated amplification|transcription-mediated amplification]],<ref name="CDC testing" /><ref name="CDC NAATs" /><ref>{{#invoke:cite journal ||vauthors=Gorzalski AJ, Tian H, Laverdure C, Morzunov S, Verma SC, VanHooser S, Pandori MW | display-authors = 6 |date=August 2020 |title=High-Throughput Transcription-mediated amplification on the Hologic Panther is a highly sensitive method of detection for SARS-CoV-2 |journal=Journal of Clinical Virology |volume=129 |pages=104501 |doi=10.1016/j.jcv.2020.104501 |pmc=7286273 |pmid=32619959}}</ref> and reverse transcription loop-mediated isothermal amplification (RT{{nbhyph}}LAMP)<ref name="CDC testing" /><ref name="CDC NAATs" /> from a [[Nasopharyngeal swab|nasopharyngeal swab]].<ref name="pmid32621814" />

Several [[Medicine:COVID-19 vaccine|COVID-19 vaccine]]s have been approved and distributed in various countries, which have initiated mass vaccination campaigns. Other [[Social:Pandemic prevention|preventive measures]] include [[Medicine:Social distancing|physical or social distancing]], [[Medicine:Quarantine|quarantining]], ventilation of indoor spaces, use of face masks or coverings in public, covering coughs and sneezes, hand washing, and keeping unwashed hands away from the face. While work is underway to [[Biology:COVID-19 drug development|develop drugs]] that inhibit the virus, the primary treatment is symptomatic. Management involves the [[Medicine:Symptomatic treatment|treatment of symptoms]] through [[Medicine:Symptomatic treatment|supportive care]], [[Medicine:Isolation (health care)|isolation]], and experimental measures.


== Nomenclature ==
{{Main|Biology:COVID-19 naming}}
During the initial outbreak in [[Place:Wuhan|Wuhan]], the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus",<ref>{{#invoke:cite news ||url=https://www.npr.org/sections/health-shots/2020/01/24/799208865/a-second-u-s-case-of-wuhan-coronavirus-is-confirmed|title=2nd U.S. Case Of Wuhan Coronavirus Confirmed|publisher=NPR|access-date=4 April 2020}}</ref><ref>{{#invoke:cite news ||vauthors=McNeil Jr DG |url=https://www.nytimes.com/2020/02/02/health/coronavirus-pandemic-china.html |archive-url=https://web.archive.org/web/20200202194034/https://www.nytimes.com/2020/02/02/health/coronavirus-pandemic-china.html |archive-date=2 February 2020 |url-access=subscription |url-status=live|title=Wuhan Coronavirus Looks Increasingly Like a Pandemic, Experts Say|date=2 February 2020|work={{wipe|The New York Times}}|access-date=4 April 2020 |issn=0362-4331}}</ref><ref>{{#invoke:cite news||url=https://www.cnn.com/2020/02/05/asia/wuhan-coronavirus-update-death-toll-spike-intl-hnk/index.html|title=Wuhan coronavirus deaths spike again as outbreak shows no signs of slowing| vauthors = Griffiths J | publisher=CNN|access-date=4 April 2020 }}</ref> with the disease sometimes called "Wuhan pneumonia".<ref>{{#invoke:cite journal ||vauthors=Jiang S, Xia S, Ying T, Lu L |date=May 2020 |title=A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome |journal=Cellular & Molecular Immunology |volume=17 |issue=5 |pages=554 |doi=10.1038/s41423-020-0372-4 |pmc=7091741 |pmid=32024976 |doi-access=free |title-link=doi}}</ref><ref>{{#invoke:cite journal ||display-authors=6 |vauthors=Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY |date=February 2020 |title=A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster |journal=Lancet |volume=395 |issue=10223 |pages=514–523 |doi=10.1016/S0140-6736(20)30154-9 |pmc=7159286 |pmid=31986261 |doi-access=free |title-link=doi}}</ref> In the past, many diseases have been named after geographical locations, such as the Spanish flu,<ref>{{#invoke:cite journal ||vauthors=Shablovsky S |date=September 2017 |title=The legacy of the Spanish flu |journal=Science |volume=357 |issue=6357 |pages=1245 |bibcode=2017Sci...357.1245S |doi=10.1126/science.aao4093 |issn=0036-8075 |doi-access=free |s2cid=44116811 |title-link=doi}}</ref> [[Medicine:Middle East respiratory syndrome|Middle East respiratory syndrome]], and [[Medicine:Zika virus|Zika virus]].<ref name="Nature Stop">{{#invoke:cite journal ||title=Stop the coronavirus stigma now |url=https://www.nature.com/articles/d41586-020-01009-0 |access-date=16 April 2020 |journal=Nature |date=7 April 2020 |volume=580 |issue=7802 |pages=165 |doi=10.1038/d41586-020-01009-0|pmid=32265571 |bibcode=2020Natur.580..165. |s2cid=214809950}}</ref> In January 2020, the [[Organization:World Health Organization|World Health Organization]] (WHO) recommended 2019-nCoV<ref>{{#invoke:cite web||url=https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200121-sitrep-1-2019-ncov.pdf|title=Novel Coronavirus (2019-nCoV) Situation Report – 1|date=21 January 2020|website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref> and 2019-nCoV acute respiratory disease<ref>{{#invoke:cite web||url=https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200130-sitrep-10-ncov.pdf|title=Novel Coronavirus(2019-nCoV) Situation Report – 10 |date=30 January 2020|website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref> as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations or groups of people in disease and virus names to prevent [[Social:Social stigma|social stigma]].<ref>{{#invoke:cite news ||title=Novel coronavirus named 'Covid-19': WHO |url=https://www.todayonline.com/world/wuhan-novel-coronavirus-named-covid-19-who |access-date=11 February 2020 |work=Today|location=Singapore |archive-url=https://archive.today/20200321085608/https://www.todayonline.com/world/wuhan-novel-coronavirus-named-covid-19-who |archive-date=21 March 2020 |url-status=live}}</ref><ref name="veconomist">{{#invoke:cite news ||title=The coronavirus spreads racism against – and among – ethnic Chinese |url=https://www.economist.com/china/2020/02/17/the-coronavirus-spreads-racism-against-and-among-ethnic-chinese |newspaper=[[Finance:The Economist|The Economist]] |date=17 February 2020 |access-date=17 February 2020 |archive-url=https://web.archive.org/web/20200217223902/https://www.economist.com/china/2020/02/17/the-coronavirus-spreads-racism-against-and-among-ethnic-chinese |archive-date=17 February 2020 |url-status=live}}</ref><ref>{{#invoke:cite report||url=https://apps.who.int/iris/bitstream/handle/10665/163636/WHO_HSE_FOS_15.1_eng.pdf|title=World Health Organization Best Practices for the Naming of New Human Infectious Diseases |date=May 2015|publisher=[[Organization:World Health Organization|World Health Organization]] (WHO) |hdl=10665/163636 |hdl-access=free}}</ref> The official names COVID‑19 and SARS-CoV-2 were issued by the WHO on 11 February 2020 with COVID-19 being shorthand for "coronavirus disease 2019".<ref name="WHO-naming">{{#invoke:cite web||url=https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it|title=Naming the coronavirus disease (COVID-19) and the virus that causes it|website=[[Organization:World Health Organization|World Health Organization]] (WHO)|access-date=13 March 2020|archive-url=https://web.archive.org/web/20200228035651/https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it|archive-date=28 February 2020|url-status=live}}</ref><ref>{{#invoke:cite web ||title=Novel Coronavirus(2019-nCoV) Situation Report – 22 |url=https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200211-sitrep-22-ncov.pdf |publisher=WHO |date=11 February 2020}}</ref> The WHO additionally uses "the COVID‑19 virus" and "the virus responsible for COVID‑19" in public communications.<ref name="WHO-naming" /><ref>{{#invoke:cite journal ||vauthors=Gover AR, Harper SB, Langton L |date=July 2020 |title=Anti-Asian Hate Crime During the COVID-19 Pandemic: Exploring the Reproduction of Inequality |journal=American Journal of Criminal Justice |volume=45 |issue=4 |pages=647–667 |doi=10.1007/s12103-020-09545-1 |pmc=7364747 |pmid=32837171}}</ref>

== Symptoms and signs ==
<!-- TO EDIT THIS SECTION, GO TO Symptoms of COVID-19. -->
{{Excerpt|Symptoms of COVID-19|hat=no}}

=== Complications ===
[[File:Fimmu-11-01648-g001.jpg|thumb|Mechanisms of SARS-CoV-2 cytokine storm and complications]]

Complications may include [[Medicine:Pneumonia|pneumonia]], [[Medicine:Acute respiratory distress syndrome|acute respiratory distress syndrome]] (ARDS), [[Medicine:Multiple organ dysfunction syndrome|multi-organ failure]], [[Medicine:Septic shock|septic shock]], and death.<ref name="Hui14Jan2020">{{#invoke:cite journal || vauthors = Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E | display-authors = 6 | title = The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – The latest 2019 novel coronavirus outbreak in Wuhan, China | journal = International Journal of Infectious Diseases | volume = 91 | pages = 264–266 | date = February 2020 | pmid = 31953166 | pmc = 7128332 | doi = 10.1016/j.ijid.2020.01.009 | title-link = doi | doi-access = free }}</ref><ref name="auto">{{#invoke:cite journal || vauthors = Murthy S, Gomersall CD, Fowler RA | title = Care for Critically Ill Patients With COVID-19 | journal = JAMA | volume = 323 | issue = 15 | pages = 1499–1500 | date = April 2020 | pmid = 32159735 | doi = 10.1001/jama.2020.3633 | doi-access = free | title-link = doi }}</ref><ref name="StatPearls">{{#invoke:cite book||title=StatPearls|vauthors=Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R|date=2020|publisher=StatPearls Publishing|location=Treasure Island (FL)|chapter=Features, Evaluation and Treatment Coronavirus (COVID-19)|pmid=32150360|access-date=18 March 2020|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK554776/}}</ref><ref name="Heymann Shindo 2020 pp. 542–545222">{{#invoke:cite journal || vauthors = Heymann DL, Shindo N | title = COVID-19: what is next for public health? | journal = Lancet | volume = 395 | issue = 10224 | pages = 542–545 | date = February 2020 | pmid = 32061313 | pmc = 7138015 | doi = 10.1016/s0140-6736(20)30374-3 | collaboration = WHO Scientific and Technical Advisory Group for Infectious Hazards }}</ref> Cardiovascular complications may include heart failure, [[Medicine:Arrhythmia|arrhythmia]]s (including [[Medicine:Atrial fibrillation|atrial fibrillation]]), [[Medicine:Myocarditis|heart inflammation]], and [[Medicine:Thrombosis|thrombosis]], particularly venous thromboembolism.<ref>{{#invoke:cite journal || vauthors = Romiti GF, Corica B, Lip GY, Proietti M | title = Prevalence and Impact of Atrial Fibrillation in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis | journal = Journal of Clinical Medicine | volume = 10 | issue = 11 | pages = 2490 | date = June 2021 | pmid = 34199857 | doi = 10.3390/jcm10112490 | pmc = 8200114 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Wen W, Zhang H, Zhou M, Cheng Y, Ye L, Chen J, Wang M, Feng Z | display-authors = 6 | title = Arrhythmia in patients with severe coronavirus disease (COVID-19): a meta-analysis | journal = European Review for Medical and Pharmacological Sciences | volume = 24 | issue = 21 | pages = 11395–11401 | date = November 2020 | pmid = 33215461 | doi = 10.26355/eurrev_202011_23632 | s2cid = 227077132 }}</ref><ref name="Long-2020">{{#invoke:cite journal || vauthors = Long B, Brady WJ, Koyfman A, Gottlieb M | title = Cardiovascular complications in COVID-19 | journal = The American Journal of Emergency Medicine | volume = 38 | issue = 7 | pages = 1504–1507 | date = July 2020 | pmid = 32317203 | pmc = 7165109 | doi = 10.1016/j.ajem.2020.04.048 }}</ref><ref>{{#invoke:cite journal || vauthors = Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, Shchendrygina A, Escher F, Vasa-Nicotera M, Zeiher AM, Vehreschild M, Nagel E | display-authors = 6 | title = Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19) | journal = JAMA Cardiology | volume = 5 | issue = 11 | pages = 1265–1273 | date = November 2020 | pmid = 32730619 | pmc = 7385689 | doi = 10.1001/jamacardio.2020.3557 | title-link = doi | doi-access = free }}</ref><ref>{{#invoke:cite journal || vauthors = Lindner D, Fitzek A, Bräuninger H, Aleshcheva G, Edler C, Meissner K, Scherschel K, Kirchhof P, Escher F, Schultheiss HP, Blankenberg S, Püschel K, Westermann D | display-authors = 6 | title = Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases | journal = JAMA Cardiology | volume = 5 | issue = 11 | pages = 1281–1285 | date = November 2020 | pmid = 32730555 | pmc = 7385672 | doi = 10.1001/jamacardio.2020.3551 | title-link = doi | doi-access = free }}</ref><ref>{{#invoke:cite journal || vauthors = Siripanthong B, Nazarian S, Muser D, Deo R, Santangeli P, Khanji MY, Cooper LT, Chahal CA | display-authors = 6 | title = Recognizing COVID-19-related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management | journal = Heart Rhythm | volume = 17 | issue = 9 | pages = 1463–1471 | date = September 2020 | pmid = 32387246 | pmc = 7199677 | doi = 10.1016/j.hrthm.2020.05.001 }}</ref> Approximately 20–30% of people who present with COVID‑19 have [[Medicine:Elevated transaminases|elevated liver enzymes]], reflecting liver injury.<ref>{{#invoke:cite journal || vauthors = Xu L, Liu J, Lu M, Yang D, Zheng X | title = Liver injury during highly pathogenic human coronavirus infections | journal = Liver International | volume = 40 | issue = 5 | pages = 998–1004 | date = May 2020 | pmid = 32170806 | pmc = 7228361 | doi = 10.1111/liv.14435 | title-link = doi | doi-access = free }}</ref><ref name="Sanders202022">{{#invoke:cite journal || vauthors = Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB | title = Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review | journal = JAMA | volume = 323 | issue = 18 | pages = 1824–1836 | date = May 2020 | pmid = 32282022 | doi = 10.1001/jama.2020.6019 | doi-access = free | title-link = doi }}</ref>

Neurologic manifestations include seizure, stroke, [[Medicine:Encephalitis|encephalitis]], and [[Medicine:Guillain–Barré syndrome|Guillain–Barré syndrome]] (which includes loss of motor functions).<ref name="Carod-Artal-2020">{{#invoke:cite journal || vauthors = Carod-Artal FJ | title = Neurological complications of coronavirus and COVID-19 | journal = Revista de Neurología | volume = 70 | issue = 9 | pages = 311–322 | date = May 2020 | pmid = 32329044 | doi = 10.33588/rn.7009.2020179 | s2cid = 226200547 }}</ref><ref>{{#invoke:cite journal || vauthors = Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, Franciotta D, Baldanti F, Daturi R, Postorino P, Cavallini A, Micieli G | display-authors = 6 | title = Guillain-Barré Syndrome Associated with SARS-CoV-2 | journal = The New England Journal of Medicine | volume = 382 | issue = 26 | pages = 2574–2576 | date = June 2020 | pmid = 32302082 | pmc = 7182017 | doi = 10.1056/NEJMc2009191 }}</ref> Following the infection, children may develop [[Medicine:Paediatric multisystem inflammatory syndrome|paediatric multisystem inflammatory syndrome]], which has symptoms similar to [[Medicine:Kawasaki disease|Kawasaki disease]], which can be fatal.<ref>{{#invoke:Cite web||title=Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 |url=https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19 |website=[[Organization:World Health Organization|World Health Organization]] (WHO) |date=15 May 2020|access-date=20 May 2020}}</ref><ref>{{#invoke:cite report ||title=HAN Archive – 00432 |url=https://emergency.cdc.gov/han/2020/han00432.asp |website=U.S. Centers for Disease Control and Prevention (CDC) |access-date=20 May 2020 |date=15 May 2020}}</ref> In very rare cases, acute encephalopathy can occur, and it can be considered in those who have been diagnosed with COVID‑19 and have an altered mental status.<ref>{{#invoke:cite journal || vauthors = Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B | title = COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: Imaging Features | journal = Radiology | volume = 296 | issue = 2 | pages = E119–E120 | date = August 2020 | pmid = 32228363 | pmc = 7233386 | doi = 10.1148/radiol.2020201187 }}</ref>

According to the US Centers for Disease Control and Prevention, pregnant women are at increased risk of becoming seriously ill from COVID‑19.<ref name="Cordoba-Vives-2020">{{#invoke:cite journal||vauthors=Córdoba-Vives S, Peñaranda G|date=April 2020|title=COVID-19 y Embarazo|url=https://revistamedicacr.com/index.php/rmcr/article/viewFile/288/265|journal=Medical Journal of Costa Rica |pages=629 |language=es|access-date=14 February 2022|archive-date=18 June 2021|archive-url=https://web.archive.org/web/20210618082133/http://revistamedicacr.com/index.php/rmcr/article/viewFile/288/265|url-status=dead}}</ref> This is because pregnant women with COVID‑19 appear to be more likely to develop respiratory and obstetric complications that can lead to [[Medicine:Miscarriage|miscarriage]], premature delivery and [[Medicine:Intrauterine growth restriction|intrauterine growth restriction]].<ref name="Cordoba-Vives-2020" />

Fungal infections such as [[Medicine:Aspergillosis|aspergillosis]], [[Medicine:Candidiasis|candidiasis]], [[Medicine:Cryptococcosis|cryptococcosis]] and [[Medicine:Mucormycosis|mucormycosis]] have been recorded in patients recovering from COVID‑19.<ref>{{#invoke:cite journal ||vauthors=Das S, Dhar S |title=Mucormycosis Following COVID-19 Infections: an Insight |journal=The Indian Journal of Surgery |volume=84| pages=585–586 |date=July 2021 |issue=3 |pmid=34276145 |pmc=8270771 |doi=10.1007/s12262-021-03028-1 |s2cid=235782159}}</ref><ref>{{#invoke:cite journal ||vauthors=Baruah C, Devi P, Deka B, Sharma DK |date=June 2021|title=Mucormycosis and Aspergillosis have been Linked to Covid-19-Related Fungal Infections in India |url=https://www.researchgate.net/publication/352554687 |journal=Advancements in Case Studies|volume=3|issue=1|doi=10.31031/AICS.2021.03.000555|s2cid=244678882|issn=2639-0531|via=[[Company:ResearchGate|ResearchGate]]}}</ref>

== Cause ==
COVID‑19 is caused by infection with a [[Biology:Strain#Microbiology and virology|strain]] of [[Biology:Coronavirus|coronavirus]] known as 'Severe Acute Respiratory Syndrome coronavirus 2' ([[Biology:SARS-CoV-2|SARS-CoV-2]]).<ref>{{#invoke:cite journal ||vauthors=Hu B, Guo H, Zhou P, Shi ZL |date=March 2021 |title=Characteristics of SARS-CoV-2 and COVID-19 |journal=Nature Reviews. Microbiology |volume=19 |issue=3 |pages=141–154 |doi=10.1038/s41579-020-00459-7 |pmc=7537588 |pmid=33024307}}</ref>

=== Transmission ===
<!-- TO EDIT THIS SECTION, GO TO Transmission of COVID-19. -->
[[File:Https-doi.org-10.1073-pnas.2009637117-F4.large.jpg|thumb|[[Medicine:Transmission|Transmission]] of COVID‑19]]
{{Excerpt|Transmission of COVID-19|paragraphs=1-4|hat=no}}

=== Virology ===
{{Main|SARS-CoV-2}}[[File:Coronavirus virion structure.svg|thumb|Illustration of [[Biology:SARSr-CoV|SARSr-CoV]] virion]]

Severe acute respiratory syndrome coronavirus{{spaces}}2 (SARS-CoV-2) is a [[Biology:Novel virus|novel]] severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the [[Medicine:Disease cluster|cluster]] of acute respiratory illness cases in Wuhan.<ref name="ECDC risk assessment">{{#invoke:Cite web||url=https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-risk-assessment-14-feb-2020.pdf |title=Outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): increased transmission beyond China – fourth update |publisher=European Centre for Disease Prevention and Control |date=14 February 2020 |access-date=8 March 2020}}</ref> All structural features of the novel SARS-CoV-2 virus particle occur in related [[Biology:Coronavirus|coronavirus]]es in nature,<ref name="NM-20200317" /> particularly in ''Rhinolophus sinicus'' aka Chinese horseshoe bats.<ref name="zhou20">{{#invoke:cite journal ||doi=10.1038/s41586-020-2012-7|title=A pneumonia outbreak associated with a new coronavirus of probable bat origin |year=2020 |last1=Zhou |first1=Peng |last2=Yang |first2=Xing-Lou |last3=Wang |first3=Xian-Guang |last4=Hu |first4=Ben |last5=Zhang |first5=Lei |last6=Zhang |first6=Wei |last7=Si |first7=Hao-Rui |last8=Zhu |first8=Yan |last9=Li |first9=Bei |last10=Huang |first10=Chao-Lin |last11=Chen |first11=Hui-Dong |last12=Chen |first12=Jing |last13=Luo |first13=Yun |last14=Guo |first14=Hua |last15=Jiang |first15=Ren-Di |last16=Liu |first16=Mei-Qin |last17=Chen |first17=Ying |last18=Shen |first18=Xu-Rui |last19=Wang |first19=Xi |last20=Zheng |first20=Xiao-Shuang |last21=Zhao |first21=Kai |last22=Chen |first22=Quan-Jiao |last23=Deng |first23=Fei |last24=Liu |first24=Lin-Lin |last25=Yan |first25=Bing |last26=Zhan |first26=Fa-Xian |last27=Wang |first27=Yan-Yi |last28=Xiao |first28=Geng-Fu |last29=Shi |first29=Zheng-Li |journal=Nature |volume=579 |issue=7798 |pages=270–273 |pmid=32015507 |pmc=7095418 |bibcode=2020Natur.579..270Z }}</ref>

Outside the human body, the virus is destroyed by household soap which bursts its [[Biology:Viral envelope|protective bubble]].<ref name="NatGeoSoap">{{#invoke:Cite web||url=https://www.nationalgeographic.com/science/2020/03/why-soap-preferable-bleach-fight-against-coronavirus/ |vauthors=Gibbens S |title=Why soap is preferable to bleach in the fight against coronavirus |date=18 March 2020 |website=National Geographic |url-status=live |archive-url=https://web.archive.org/web/20200402001042/https://www.nationalgeographic.com/science/2020/03/why-soap-preferable-bleach-fight-against-coronavirus/ |archive-date=2 April 2020 |access-date=2 April 2020}}</ref> Hospital disinfectants, alcohols, heat, [[Chemistry:Povidone-iodine|povidone-iodine]], and [[Physics:Ultraviolet|ultraviolet-C]] (UV-C) irradiation are also effective disinfection methods for surfaces.<ref>{{#invoke:cite journal ||last1=Viana Martins |first1=C. P. |last2=Xavier |first2=C. S. F. |last3=Cobrado |first3=L. |date=2022 |title=Disinfection methods against SARS-CoV-2: a systematic review |url= |journal=The Journal of Hospital Infection |volume=119 |pages=84–117 |doi=10.1016/j.jhin.2021.07.014 |issn=1532-2939 |pmc=8522489 |pmid=34673114}}</ref>

SARS-CoV-2 is closely related to the original SARS-CoV.<ref name="Zhu24Jan2020">{{#invoke:cite journal ||vauthors=Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W |display-authors=6 |title=A Novel Coronavirus from Patients with Pneumonia in China, 2019 |journal=The New England Journal of Medicine |volume=382 |issue=8 |pages=727–733 |date=February 2020 |pmid=31978945 |pmc=7092803 |doi=10.1056/NEJMoa2001017}}</ref> It is thought to have an animal ([[Biology:Zoonosis|zoonotic]]) origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus ''[[Biology:Betacoronavirus|Betacoronavirus]]'', in subgenus [[Biology:Severe acute respiratory syndrome–related coronavirus|''Sarbecovirus'']] (lineage B) together with two bat-derived strains. It is 96% identical at the whole [[Biology:Genome|genome]] level to other bat coronavirus samples (BatCov [[Biology:RaTG13|RaTG13]]).<ref name="WHOReport24Feb2020">{{#invoke:cite report ||url=https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf |title=Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) |date=February 2020 |publisher=[[Organization:World Health Organization|World Health Organization]] (WHO) |access-date=21 March 2020 |archive-url=https://web.archive.org/web/20200229221222/https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf |archive-date=29 February 2020 |url-status=live}}</ref><ref>{{#invoke:Cite web|| title=Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) | publisher=[[Organization:World Health Organization|World Health Organization]] (WHO) | url=https://www.who.int/publications/i/item/report-of-the-who-china-joint-mission-on-coronavirus-disease-2019-(covid-19) | access-date=25 January 2022}}</ref><ref name="RathoreSingh">{{#invoke:cite journal || vauthors = Rathore JS, Ghosh C | title = Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a newly emerged pathogen: an overview | journal = Pathogens and Disease | volume = 78 | issue = 6 | date = August 2020 | pmid = 32840560 | pmc = 7499575 | doi = 10.1093/femspd/ftaa042 | oclc = 823140442 | doi-access = free | title-link = doi }}</ref> The structural proteins of SARS-CoV-2 include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and the spike protein (S). The M protein of SARS-CoV-2 is about 98% similar to the M protein of bat SARS-CoV, maintains around 98% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only around 38% with the M protein of MERS-CoV.<ref>{{#invoke:cite journal || vauthors = Thomas S | title = The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET | journal = Pathogens & Immunity | volume = 5 | issue = 1 | pages = 342–363 | date = October 2020 | pmid = 33154981 | pmc = 7608487 | doi = 10.20411/pai.v5i1.377 }}</ref>

=== SARS-CoV-2 variants ===

The many thousands of SARS-CoV-2 variants are grouped into either [[Biology:Clade|clade]]s or [[Biology:Lineage (evolution)|lineages]].<ref>{{#invoke:cite journal ||vauthors = Koyama T, Platt D, Parida L |title=Variant analysis of SARS-CoV-2 genomes |journal=Bulletin of the World Health Organization |volume=98 |issue=7 |pages=495–504 |date=July 2020 |pmid=32742035 |pmc=7375210 |doi=10.2471/BLT.20.253591 |quote=We detected in total 65776 variants with 5775 distinct variants.}}</ref><ref name="Rambaut-2020"/> The WHO, in collaboration with partners, expert networks, national authorities, institutions and researchers, have established nomenclature systems for naming and tracking SARS-CoV-2 genetic lineages by [[Organization:GISAID|GISAID]], [[Organization:Nextstrain|Nextstrain]] and [[Software:Phylogenetic Assignment of Named Global Outbreak Lineages|Pango]]. The expert group convened by the WHO recommended the labelling of variants using letters of the Greek alphabet, for example, Alpha, Beta, Delta, and Gamma, giving the justification that they "will be easier and more practical to discussed by non-scientific audiences."<ref>{{#invoke:Cite web||date=1 July 2021|title=Tracking SARS-CoV-2 variants|url=https://www.who.int/activities/tracking-SARS-CoV-2-variants|access-date=5 July 2021|website=[[Organization:World Health Organization|World Health Organization]]}}</ref> [[Organization:Nextstrain|Nextstrain]] divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while [[Organization:GISAID|GISAID]] divides them into seven (L, O, V, S, G, GH, and GR).<ref name="Alm2020Aug">{{#invoke:cite journal ||vauthors=Alm E, Broberg EK, Connor T, Hodcroft EB, Komissarov AB, Maurer-Stroh S, Melidou A, Neher RA, O'Toole Á, Pereyaslov D |display-authors=6 |title=Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020 |journal=Euro Surveillance |volume=25 |issue=32 |date=August 2020 |pmid=32794443 |pmc=7427299 |doi=10.2807/1560-7917.ES.2020.25.32.2001410}}</ref> The Pango tool groups variants into [[Biology:Lineage (evolution)|lineages]], with many circulating lineages being classed under the B.1 lineage.<ref name="Rambaut-2020">{{#invoke:cite journal ||vauthors=Rambaut A, Holmes EC, O'Toole Á, Hill V, McCrone JT, Ruis C, du Plessis L, Pybus OG |display-authors=6 |title=A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology |journal=Nature Microbiology |volume=5 |issue=11 |pages=1403–1407 |date=November 2020 |pmid=32669681 |pmc=7610519 |doi=10.1038/s41564-020-0770-5}}</ref><ref>{{#invoke:Cite web||title=PANGO lineages|url=https://cov-lineages.org/pango_lineages.html|access-date=9 May 2021|url-status=dead |website=cov-lineages.org|archive-date=10 May 2021|archive-url=https://web.archive.org/web/20210510111318/https://cov-lineages.org/pango_lineages.html}}</ref>

Several notable variants of SARS-CoV-2 emerged throughout 2020.<ref name="Lauring Hodcroft 2021 pp. 529–531">{{#invoke:cite journal ||vauthors=Lauring AS, Hodcroft EB |title=Genetic Variants of SARS-CoV-2-What Do They Mean? |journal=JAMA |volume=325 |issue=6 |pages=529–531 |date=February 2021 |pmid=33404586 |s2cid=230783233 |doi=10.1001/jama.2020.27124 |doi-access=free |title-link=doi}}</ref><ref name="Abdool Karim de Oliveira pp. 1866–1868">{{#invoke:cite journal ||vauthors=Abdool Karim SS, de Oliveira T |title=New SARS-CoV-2 Variants – Clinical, Public Health, and Vaccine Implications |journal=The New England Journal of Medicine |volume=384 |issue=19 |pages=1866–1868 |date=May 2021 |pmid=33761203 |doi=10.1056/nejmc2100362| issn=0028-4793 |publisher=Massachusetts Medical Society |pmc=8008749}}</ref> Cluster 5 emerged among [[Biology:Mink|mink]]s and mink farmers in {{wipe|Denmark}}.<ref>{{#invoke:cite journal ||vauthors=Mallapaty S |title=COVID mink analysis shows mutations are not dangerous – yet |journal=Nature |volume=587 |issue=7834 |pages=340–341 |date=November 2020 |pmid=33188367 |doi=10.1038/d41586-020-03218-z |doi-access=free |s2cid=226947606 |bibcode=2020Natur.587..340M}}</ref> After strict quarantines and a mink euthanasia campaign, the cluster was assessed to no longer be circulating among humans in Denmark as of 1 February 2021.<ref>{{#invoke:cite journal ||vauthors=Larsen HD, Fonager J, Lomholt FK, Dalby T, Benedetti G, Kristensen B, Urth TR, Rasmussen M, Lassaunière R, Rasmussen TB, Strandbygaard B, Lohse L, Chaine M, Møller KL, Berthelsen AN, Nørgaard SK, Sönksen UW, Boklund AE, Hammer AS, Belsham GJ, Krause TG, Mortensen S, Bøtner A, Fomsgaard A, Mølbak K |display-authors=6 |title=Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020 |journal=Euro Surveillance |volume=26 |issue=5 |pages=2100009 |date=February 2021 |pmid=33541485 |pmc=7863232 |doi=10.2807/1560-7917.ES.2021.26.5.210009 |quote=As at 1 February 2021, we assess that the cluster 5 variant is no longer circulating among humans in Denmark.}}</ref>

{{as of|2021|12}}, there are five dominant variants of SARS-CoV-2 spreading among global populations: the Alpha variant (B.1.1.7, formerly called the UK variant), first found in London and Kent, the Beta variant (B.1.351, formerly called the South Africa variant), the Gamma variant (P.1, formerly called the Brazil variant), the Delta variant (B.1.617.2, formerly called the India variant),<ref>{{#invoke:Cite web||title=New COVID-19 Variants|url=https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant.html|access-date=15 July 2021|website=U.S. Centers for Disease Control and Prevention (CDC)|date=28 June 2021|orig-date=First published 11 February 2020}}</ref> and the Omicron variant (B.1.1.529), which had spread to 57 countries as of 7 December.<ref>{{#invoke:Cite web||url=https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---7-december-2021 |title=COVID-19 Weekly Epidemiological Update Edition 69 |website=[[Organization:World Health Organization|World Health Organization]] (WHO) |date=7 December 2021}}</ref><ref>{{#invoke:Cite web||title=Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern |url=https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern |access-date=9 December 2021 |website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref>

On December 19, 2023, the WHO declared that another distinctive variant, JN.1, had emerged as a "variant of interest." Though the WHO expects an increase in cases globally, particularly for countries entering winter, the current overall global health risk (as of December 21, 2023) remains low.<ref>{{Cite web |date=December 19, 2023 |title=JN.1 |url=https://www.who.int/docs/default-source/coronaviruse/18122023_jn.1_ire_clean.pdf?sfvrsn=6103754a_3 |access-date=December 21, 2023}}</ref><ref>{{Cite web |last=Benadjaoud |first=Youri |date=2023-12-19 |title=COVID variant JN.1 listed as 'variant of interest' by World Health Organization |url=https://abcnews.go.com/Health/covid-variant-jn1-listed-variant-interest-world-health/story?id=105782742 |access-date=2023-12-22 |website=ABC News |language=en}}</ref>

== Pathophysiology ==
[[File:Fpubh-08-00383-g003.jpg|thumb|COVID‑19 [[Medicine:Pathogenesis|pathogenesis]]]]

The SARS-CoV-2 virus can infect a wide range of cells and systems of the body. COVID‑19 is most known for affecting the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs).<ref name="pmid33132005">{{#invoke:cite journal || vauthors = Harrison AG, Lin T, Wang P | title = Mechanisms of SARS-CoV-2 Transmission and Pathogenesis | journal = Trends in Immunology | volume = 41 | issue = 12 | pages = 1100–1115 | date = December 2020 | pmid = 33132005 | pmc = 7556779 | doi = 10.1016/j.it.2020.10.004 }}</ref> The lungs are the organs most affected by COVID‑19 because the virus accesses host cells via the [[Biology:Receptor (biochemistry)|receptor]] for the enzyme [[Biology:Angiotensin-converting enzyme 2|angiotensin-converting enzyme 2]] (ACE2), which is most abundant on the surface of type II alveolar cells of the lungs.<ref>{{#invoke:cite journal || vauthors = Verdecchia P, Cavallini C, Spanevello A, Angeli F | title = The pivotal link between ACE2 deficiency and SARS-CoV-2 infection | journal = European Journal of Internal Medicine | volume = 76 | pages = 14–20 | date = June 2020 | pmid = 32336612 | pmc = 7167588 | doi = 10.1016/j.ejim.2020.04.037 }}</ref> The virus uses a special surface glycoprotein called a "spike" to connect to the ACE2 receptor and enter the host cell.<ref name="Nature Microbiology">{{#invoke:cite journal || vauthors = Letko M, Marzi A, Munster V | title = Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses | journal = Nature Microbiology | volume = 5 | issue = 4 | pages = 562–569 | date = April 2020 | pmid = 32094589 | pmc = 7095430 | doi = 10.1038/s41564-020-0688-y | doi-access = free | title-link = doi }}</ref>

=== Respiratory tract ===
Following viral entry, COVID‑19 infects the ciliated epithelium of the nasopharynx and upper airways.<ref>{{#invoke:cite journal || vauthors = Marik PE, Iglesias J, Varon J, Kory P | title = A scoping review of the pathophysiology of COVID-19 | journal = International Journal of Immunopathology and Pharmacology | volume = 35 | pages = 20587384211048026 | date = January 2021 | pmid = 34569339 | pmc = 8477699 | doi = 10.1177/20587384211048026 }}</ref>

Autopsies of people who died of COVID‑19 have found [[Medicine:Diffuse alveolar damage|diffuse alveolar damage]], and lymphocyte-containing inflammatory infiltrates within the lung.<ref name="Cureus">{{#invoke:cite journal || vauthors = Eketunde AO, Mellacheruvu SP, Oreoluwa P | title = A Review of Postmortem Findings in Patients With COVID-19 | journal = Cureus | volume = 12 | issue = 7 | pages = e9438 | date = July 2020 | pmid = 32864262 | pmc = 7451084 | doi = 10.7759/cureus.9438 | publisher = Cureus, Inc. | s2cid = 221352704 | doi-access = free | title-link = doi }}</ref>

=== Nervous system ===
One common symptom, loss of smell, results from infection of the support cells of the olfactory epithelium, with subsequent damage to the [[Biology:Olfactory receptor neuron|olfactory neurons]].<ref name="Meunier-2020">{{#invoke:cite journal ||vauthors = Meunier N, Briand L, Jacquin-Piques A, Brondel L, Pénicaud L |title = COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology |journal = Frontiers in Physiology |volume = 11 |pages = 625110 |date = June 2020 |pmid = 33574768 |pmc = 7870487 |doi = 10.3389/fphys.2020.625110 |doi-access = free |title-link = doi }}</ref> The involvement of both the central and peripheral nervous system in COVID‑19 has been reported in many medical publications.<ref name="Guerrero2020">{{#invoke:cite journal ||vauthors = Guerrero JI, Barragán LA, Martínez JD, Montoya JP, Peña A, Sobrino FE, Tovar-Spinoza Z, Ghotme KA |display-authors=6 |title = Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings |journal = BMC Infectious Diseases |date = June 2021 |volume = 21 |issue = 1 |page = 515 |doi = 10.1186/s12879-021-06185-6| pmid = 34078305 |pmc = 8170436 |doi-access=free |title-link=doi }}</ref> It is clear that many people with COVID-19 exhibit neurological or mental health issues. The virus is not detected in the [[Biology:Central nervous system|central nervous system]] (CNS) of the majority of COVID-19 patients with neurological issues. However, SARS-CoV-2 has been detected at low levels in the brains of those who have died from COVID‑19, but these results need to be confirmed.<ref name="Pezzini2020">{{#invoke:cite journal ||vauthors = Pezzini A, Padovani A |title = Lifting the mask on neurological manifestations of COVID-19 |journal = Nature Reviews. Neurology |volume = 16 |issue = 11 |pages = 636–644 |date = November 2020 |pmid = 32839585 |pmc = 7444680 |doi = 10.1038/s41582-020-0398-3 }}</ref> While virus has been detected in [[Biology:Cerebrospinal fluid|cerebrospinal fluid]] of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain.<ref>{{#invoke:cite journal ||vauthors = Li YC, Bai WZ, Hashikawa T |title = The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients |journal = Journal of Medical Virology |volume = 92 |issue = 6 |pages = 552–555 |date = June 2020 |pmid = 32104915 |pmc = 7228394 |doi = 10.1002/jmv.25728 |title-link = doi |doi-access = free }}</ref><ref>{{#invoke:cite journal ||vauthors = Baig AM, Khaleeq A, Ali U, Syeda H |title = Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms |journal = ACS Chemical Neuroscience |volume = 11 |issue = 7 |pages = 995–998 |date = April 2020 |pmid = 32167747 |pmc = 7094171 |doi= 10.1021/acschemneuro.0c00122 }}</ref><ref>{{#invoke:cite journal ||vauthors = Yavarpour-Bali H, Ghasemi-Kasman M |title = Update on neurological manifestations of COVID-19 |journal = Life Sciences |volume = 257 |pages = 118063 |date = September 2020 |pmid = 32652139 |pmc = 7346808 |doi = 10.1016/j.lfs.2020.118063 }}</ref> The virus may also enter the bloodstream from the lungs and cross the blood–brain barrier to gain access to the CNS, possibly within an infected white blood cell.<ref name="Pezzini2020" />
[[File:Ijms-21-05932-g003.webp|thumb|[[Biology:Host tropism|Tropism]] and multiple organ injuries in SARS-CoV-2 infection]] Research conducted when Alpha was the dominant variant has suggested COVID-19 may cause brain damage.<ref>{{Cite journal |last1=Douaud |first1=Gwenaëlle |last2=Lee |first2=Soojin |last3=Alfaro-Almagro |first3=Fidel |last4=Arthofer |first4=Christoph |last5=Wang |first5=Chaoyue |last6=McCarthy |first6=Paul |last7=Lange |first7=Frederik |last8=Andersson |first8=Jesper L. R. |last9=Griffanti |first9=Ludovica |last10=Duff |first10=Eugene |last11=Jbabdi |first11=Saad |last12=Taschler |first12=Bernd |last13=Keating |first13=Peter |last14=Winkler |first14=Anderson M. |last15=Collins |first15=Rory |last16=Matthews |first16= Paul M. |last17=Naomi |first17=Allen |last18=Miller |first18=Karla L. |last19=Nichols |first19=Thomas E. |last20=Smith |first20=Stephen M. |date=March 2022 |title=SARS-CoV-2 is associated with changes in brain structure in UK Biobank |journal=Nature |volume=604 |issue=7907 |pages=697–707 |doi=10.1038/s41586-022-04569-5 |issn=1476-4687 |lccn=12037118 |oclc=01586310 |pmc=9046077 |pmid=35255491 |bibcode=2022Natur.604..697D |doi-access=free}}</ref> Later research showed that all variants studied (including Omicron) killed brain cells, but the exact cells killed varied by variant.<ref>{{Cite journal |last1=Proust |first1=Alizé
|last2= Queval|first2= Christophe J. |last3= Harvey|first3= Ruth |last4= Adams|first4= Lorin |last5= Bennett|first5= Michael |last6= Wilkinson |first6= Robert J.|date= 2023 |title= Diferential efects of SARS-CoV-2 variants on central nervous system cells and blood–brain barrier functions|journal= Journal of Neuroinflammation |volume=20 |issue=184 |page=184
|doi=10.1186/s12974-023-02861-3
|pmid=37537664
|pmc=10398935
|doi-access=free
}}</ref> It is unknown if such damage is temporary or permanent.<ref>{{Cite news |last1=Geddes |first1=Linda |last2=Sample |first2=Ian |date=7 March 2022 |title=Covid can shrink brain and damage its tissue, finds research |work={{wipe|The Guardian}} |url=https://www.theguardian.com/world/2022/mar/07/covid-can-shrink-brain-and-damage-its-tissue-finds-research |url-status=live |access-date=4 September 2023 |archive-url=https://web.archive.org/web/20220307161107/https://www.theguardian.com/world/2022/mar/07/covid-can-shrink-brain-and-damage-its-tissue-finds-research |archive-date=7 March 2022}}</ref><ref>{{Cite news |last=Morelle |first=Rebecca |date=7 March 2022 |title=Scans reveal how Covid may change the brain |work=BBC News |publisher=BBC |url=https://www.bbc.com/news/health-60591487 |url-status= |access-date=4 September 2023}}</ref> Observed individuals infected with COVID-19 (most with mild cases) experienced an additional 0.2% to 2% of brain tissue lost in regions of the brain connected to the sense of smell compared with uninfected individuals, and the overall effect on the brain was equivalent on average to at least one extra year of normal ageing; infected individuals also scored lower on several cognitive tests. All effects were more pronounced among older ages.<ref>{{#invoke:Cite web||url=https://www.nbcnews.com/health/health-news/long-covid-even-mild-covid-linked-damage-brain-months-infection-rcna18959|title=Even mild Covid is linked to brain damage months after illness, scans show |date=7 March 2022 |publisher=NBC News}}</ref>

=== Gastrointestinal tract ===
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of [[Biology:Stomach|gastric]], [[Biology:Duodenum|duodenal]] and [[Biology:Rectum|rectal]] [[Biology:Epithelium|epithelium]]<ref name="Gu-2020">{{#invoke:cite journal || vauthors = Gu J, Han B, Wang J | title = COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission | journal = Gastroenterology | volume = 158 | issue = 6 | pages = 1518–1519 | date = May 2020 | pmid = 32142785 | pmc = 7130192 | doi = 10.1053/j.gastro.2020.02.054 }}</ref> as well as [[Biology:Endothelium|endothelial]] cells and [[Biology:Enterocyte|enterocyte]]s of the [[Biology:Small intestine|small intestine]].<ref name="pmid32343593">{{#invoke:cite journal || vauthors = Mönkemüller K, Fry L, Rickes S | title = COVID-19, coronavirus, SARS-CoV-2 and the small bowel | journal = Revista Espanola de Enfermedades Digestivas | volume = 112 | issue = 5 | pages = 383–388 | date = May 2020 | pmid = 32343593 | doi = 10.17235/reed.2020.7137/2020 | s2cid = 216645754 }}</ref>

=== Cardiovascular system ===
The virus can cause [[Medicine:Myocardial infarction|acute myocardial injury]] and chronic damage to the [[Biology:Circulatory system|cardiovascular system]].<ref>{{#invoke:cite journal || vauthors = Almamlouk R, Kashour T, Obeidat S, Bois MC, Maleszewski JJ, Omrani OA, Tleyjeh R, Berbari E, Chakhachiro Z, Zein-Sabatto B, Gerberi D, Tleyjeh IM, Paniz Mondolfi AE, Finn AV, Duarte-Neto AN, Rapkiewicz AV, Frustaci A, Keresztesi AA, Hanley B, Märkl B, Lardi C, Bryce C, Lindner D, Aguiar D, Westermann D, Stroberg E, Duval EJ, Youd E, Bulfamante GP, Salmon I, Auer J, Maleszewski JJ, Hirschbühl K, Absil L, Barton LM, Ferraz da Silva LF, Moore L, Dolhnikoff M, Lammens M, Bois MC, Osborn M, Remmelink M, Nascimento Saldiva PH, Jorens PG, Craver R, Aparecida de Almeida Monteiro R, Scendoni R, Mukhopadhyay S, Suzuki T, Mauad T, Fracasso T, Grimes Z | display-authors = 6 | title = COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review | journal = Clinical Microbiology and Infection | volume = 28 | issue = 8 | pages = 1066–1075 | date = August 2022 | pmid = 35339672 | pmc = 8941843 | doi = 10.1016/j.cmi.2022.03.021 }}</ref><ref name="Zheng-2020">{{#invoke:cite journal || vauthors = Zheng YY, Ma YT, Zhang JY, Xie X | title = COVID-19 and the cardiovascular system | journal = Nature Reviews. Cardiology | volume = 17 | issue = 5 | pages = 259–260 | date = May 2020 | pmid = 32139904 | pmc = 7095524 | doi = 10.1038/s41569-020-0360-5 }}</ref> An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China,<ref name="Huang24Jan2020" /> and is more frequent in severe disease.<ref>{{#invoke:Cite web|| title=Coronavirus disease 2019 (COVID-19): Myocardial infarction and other coronary artery disease issues | website=UpToDate | url=https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-myocardial-infarction-and-other-coronary-artery-disease-issues | access-date=28 September 2020}}</ref> Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart.<ref name="Zheng-2020" /> ACE2 receptors are highly expressed in the heart and are involved in heart function.<ref name="Zheng-2020" /><ref>{{#invoke:cite journal || vauthors = Turner AJ, Hiscox JA, Hooper NM | title = ACE2: from vasopeptidase to SARS virus receptor | journal = Trends in Pharmacological Sciences | volume = 25 | issue = 6 | pages = 291–4 | date = June 2004 | pmid = 15165741 | pmc = 7119032 | doi = 10.1016/j.tips.2004.04.001 | doi-access = free | title-link = doi }}</ref>

A high incidence of [[Medicine:Thrombosis|thrombosis]] and venous thromboembolism occurs in people transferred to [[Medicine:Intensive care unit|intensive care unit]]s with COVID‑19 infections, and may be related to poor prognosis.<ref>{{#invoke:cite journal || vauthors = Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L | title = The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management | journal = Thrombosis Research | volume = 194 | pages = 101–115 | date = October 2020 | pmid = 32788101 | pmc = 7305763 | doi = 10.1016/j.thromres.2020.06.029 | publisher = Elsevier BV }}</ref> Blood vessel dysfunction and clot formation (as suggested by high [[Chemistry:D-dimer|D-dimer]] levels caused by blood clots) may have a significant role in mortality, incidents of clots leading to [[Medicine:Pulmonary embolism|pulmonary embolism]]s, and [[Medicine:Stroke|ischaemic events]] (strokes) within the brain found as complications leading to death in people infected with COVID‑19.<ref name=Science/> Infection may initiate a chain of [[Chemistry:Vasoconstriction|vasoconstrictive responses]] within the body, including pulmonary vasoconstriction {{ndash}} a possible mechanism in which oxygenation decreases during pneumonia.<ref name="Science">{{#invoke:cite journal || vauthors = Wadman M |doi=10.1126/science.abc3208 |title=How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes |journal=Science |date=April 2020 |doi-access = free | title-link = doi }}</ref> Furthermore, damage of arterioles and capillaries was found in brain tissue samples of people who died from COVID‑19.<ref>{{#invoke:cite news ||title=NIH study uncovers blood vessel damage and inflammation in COVID-19 patients' brains but no infection |url=https://www.nih.gov/news-events/news-releases/nih-study-uncovers-blood-vessel-damage-inflammation-covid-19-patients-brains-no-infection |access-date=17 January 2021 |work=National Institutes of Health (NIH) |date=30 December 2020 }}</ref><ref>{{#invoke:cite journal || vauthors = Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A | display-authors = 6 | title = Microvascular Injury in the Brains of Patients with Covid-19 | journal = The New England Journal of Medicine | volume = 384 | issue = 5 | pages = 481–483 | date = February 2021 | pmid = 33378608 | pmc = 7787217 | doi = 10.1056/nejmc2033369 }}</ref>

COVID{{nbhyph}}19 may also cause substantial structural changes to [[Biology:Blood cell|blood cell]]s, sometimes persisting for months after hospital discharge.<ref>{{#invoke:cite journal || vauthors = Kubánková M, Hohberger B, Hoffmanns J, Fürst J, Herrmann M, Guck J, Kräter M | display-authors = 6 | title = Physical phenotype of blood cells is altered in COVID-19 | journal = Biophysical Journal | volume = 120 | issue = 14 | pages = 2838–2847 | date = July 2021 | pmid = 34087216 | pmc = 8169220 | doi = 10.1016/j.bpj.2021.05.025 | bibcode = 2021BpJ...120.2838K }}</ref> A low level of blood lymphocytes may result from the virus acting through ACE2-related entry into lymphocytes.<ref>{{#invoke:cite journal||display-authors=6 | vauthors = Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MS, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW |title=Extrapulmonary manifestations of COVID-19 |journal=Nature Medicine |date=July 2020 |volume=26 |issue=7 |pages=1017–1032 |doi=10.1038/s41591-020-0968-3|pmid=32651579 |s2cid=220462000 | doi-access=free | title-link=doi }}</ref>

===Kidneys===
Another common cause of death is complications related to the kidneys.<ref name="Science" /> Early reports show that up to 30% of hospitalised patients both in China and in New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.<ref>{{#invoke:Cite web|| title=Coronavirus: Kidney Damage Caused by COVID-19 | website=Johns Hopkins Medicine | date=14 May 2020 | url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/coronavirus-kidney-damage-caused-by-covid19 | access-date=25 January 2022}}</ref>

=== Immunopathology ===
[[File:Fimmu-11-579250-g003.jpg|thumb|Key components of the [[Biology:Adaptive immune system|adaptive immune response]] to SARS-CoV-2]]

Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, people with severe COVID‑19 have symptoms of systemic hyperinflammation. Clinical laboratory findings<!-- Spellings in this paragraph have been meticulously compared link-by-link; if you spot an error, please correct the other article first. --> of elevated [[Biology:Interleukin 2|IL{{nbh}}2]], [[Medicine:Interleukin 7|IL{{nbh}}7]], IL{{nbh}}6, [[Chemistry:Granulocyte-macrophage colony-stimulating factor|granulocyte-macrophage colony-stimulating factor]] (GM{{nbh}}CSF), [[Biology:CXCL10|interferon gamma-induced protein{{spaces}}10]] (IP{{nbh}}10), monocyte chemoattractant protein{{spaces}}1 (MCP1), [[Biology:CCL3|macrophage inflammatory protein 1{{nbh}}alpha]] (MIP{{nbh}}1{{nbh}}alpha), and tumour necrosis factor (TNF{{nbh}}α) indicative of [[Medicine:Cytokine release syndrome|cytokine release syndrome]] (CRS) suggest an underlying immunopathology.<ref name="Huang24Jan2020" />

Interferon alpha plays a complex, Janus-faced role in the pathogenesis of COVID-19. Although it promotes the elimination of virus-infected cells, it also upregulates the expression of ACE-2, thereby facilitating the SARS-Cov2 virus to enter cells and to replicate.<ref>{{#invoke:cite journal ||last1=Ziegler |first1=CGK |last2=Allon |first2=SJ |last3=Nyquist |first3=SK |last4=Mbano |first4=IM |last5=Miao |first5=VN |last6=Tzouanas |first6=CN |last7=Cao |first7=Y |last8=Yousif |first8=AS |last9=Bals |first9=J |last10=Hauser |first10=BM |last11=Feldman |first11=J |last12=Muus |first12=C |last13=Wadsworth |first13=MH |last14=Kazer |first14=SW |last15=Hughes |first15=TK |last16=Doran |first16=B |last17=Gatter |first17=GJ |last18=Vukovic |first18=M |last19=Taliaferro |first19=F |last20=Mead |first20=BE |last21=Guo |first21=Z |last22=Wang |first22=JP |last23=Gras |first23=D |last24=Plaisant |first24=M |last25=Ansari |first25=M |last26=Angelidis |first26=I |last27=Adler |first27=H |last28=Sucre |first28=JMS |last29=Taylor |first29=CJ |last30=Lin |first30=B |last31=Waghray |first31=A |last32=Mitsialis |first32=V |last33=Dwyer |first33=DF |last34=Buchheit |first34=KM |last35=Boyce |first35=JA |last36=Barrett |first36=NA |last37=Laidlaw |first37=TM |last38=Carroll |first38=SL |last39=Colonna |first39=L |last40=Tkachev |first40=V |last41=Peterson |first41=CW |last42=Yu |first42=A |last43=Zheng |first43=HB |last44=Gideon |first44=HP |last45=Winchell |first45=CG |last46=Lin |first46=PL |last47=Bingle |first47=CD |last48=Snapper |first48=SB |last49=Kropski |first49=JA |last50=Theis |first50=FJ |last51=Schiller |first51=HB |last52=Zaragosi |first52=LE |last53=Barbry |first53=P |last54=Leslie |first54=A |last55=Kiem |first55=HP |last56=Flynn |first56=JL |last57=Fortune |first57=SM |last58=Berger |first58=B |last59=Finberg |first59=RW |last60=Kean |first60=LS |last61=Garber |first61=M |last62=Schmidt |first62=AG |last63=Lingwood |first63=D |last64=Shalek |first64=AK |last65=Ordovas-Montanes |first65=J |title=SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. |journal=Cell |series=HCA Lung Biological Network |date=28 May 2020 |volume=181 |issue=5 |pages=1016–1035.e19 |doi=10.1016/j.cell.2020.04.035 |pmid=32413319|pmc=7252096 }}</ref><ref>{{#invoke:cite journal ||last1=Sajuthi |first1=SP |last2=DeFord |first2=P |last3=Li |first3=Y |last4=Jackson |first4=ND |last5=Montgomery |first5=MT |last6=Everman |first6=JL |last7=Rios |first7=CL |last8=Pruesse |first8=E |last9=Nolin |first9=JD |last10=Plender |first10=EG |last11=Wechsler |first11=ME |last12=Mak |first12=ACY |last13=Eng |first13=C |last14=Salazar |first14=S |last15=Medina |first15=V |last16=Wohlford |first16=EM |last17=Huntsman |first17=S |last18=Nickerson |first18=DA |last19=Germer |first19=S |last20=Zody |first20=MC |last21=Abecasis |first21=G |last22=Kang |first22=HM |last23=Rice |first23=KM |last24=Kumar |first24=R |last25=Oh |first25=S |last26=Rodriguez-Santana |first26=J |last27=Burchard |first27=EG |last28=Seibold |first28=MA |title=Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium. |journal=Nature Communications |date=12 October 2020 |volume=11 |issue=1 |pages=5139 |doi=10.1038/s41467-020-18781-2 |pmid=33046696|pmc=7550582 |bibcode=2020NatCo..11.5139S }}</ref> A competition of negative feedback loops (via protective effects of interferon alpha) and positive feedback loops (via upregulation of ACE-2) is assumed to determine the fate of patients suffering from COVID-19.<ref>{{#invoke:cite journal ||last1=Tretter |first1=F |last2=Peters |first2=EMJ |last3=Sturmberg |first3=J |last4=Bennett |first4=J |last5=Voit |first5=E |last6=Dietrich |first6=JW |last7=Smith |first7=G |last8=Weckwerth |first8=W |last9=Grossman |first9=Z |last10=Wolkenhauer |first10=O |last11=Marcum |first11=JA |title=Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology. |journal=Journal of Evaluation in Clinical Practice |date=28 September 2022 |volume=29 |issue=3 |pages=415–429 |doi=10.1111/jep.13772 |pmid=36168893|pmc=9538129 |s2cid=252566067 }}</ref>

Additionally, people with COVID‑19 and [[Medicine:Acute respiratory distress syndrome|acute respiratory distress syndrome]] (ARDS) have classical [[Biology:Serum (blood)|serum]] [[Medicine:Biomarker|biomarkers]] of CRS, including elevated [[Chemistry:C-reactive protein|C-reactive protein]] (CRP), [[Biology:Lactate dehydrogenase|lactate dehydrogenase]] (LDH), [[Chemistry:D-dimer|D-dimer]], and [[Biology:Ferritin|ferritin]].<ref>{{#invoke:cite journal || vauthors = Zhang C, Wu Z, Li JW, Zhao H, Wang GQ | title = Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality | journal = International Journal of Antimicrobial Agents | volume = 55 | issue = 5 | pages = 105954 | date = May 2020 | pmid = 32234467 | pmc = 7118634 | doi = 10.1016/j.ijantimicag.2020.105954 }}</ref>

Systemic inflammation results in [[Medicine:Vasodilation|vasodilation]], allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T&nbsp;cells were shown to correlate with the recruitment of inflammatory IL-6-secreting [[Biology:Monocyte|monocyte]]s and severe lung pathology in people with COVID‑19.<ref>{{#invoke:cite journal || vauthors = Gómez-Rial J, Rivero-Calle I, Salas A, Martinón-Torres F | title = Role of Monocytes/Macrophages in Covid-19 Pathogenesis: Implications for Therapy | journal = Infection and Drug Resistance | volume = 13 | pages = 2485–2493 | year = 2020 | pmid = 32801787 | pmc = 7383015 | doi = 10.2147/IDR.S258639 | doi-access = free | title-link = doi }}</ref> Lymphocytic infiltrates have also been reported at autopsy.<ref name="Cureus" />

=== Viral and host factors ===

==== Virus proteins ====
[[File:Fpubh-08-00383-g004.jpg|thumb|The association between SARS-CoV-2 and the [[Medicine:Renin–angiotensin system|Renin-Angiotensin-Aldosterone System]] (RAAS)]]

Multiple viral and host factors affect the pathogenesis of the virus. The S-protein, otherwise known as the spike protein, is the viral component that attaches to the host receptor via the [[Biology:Angiotensin-converting enzyme 2|ACE2]] receptors. It includes two subunits: S1 and S2. S1 determines the virus-host range and cellular tropism via the receptor-binding domain. S2 mediates the membrane fusion of the virus to its potential cell host via the H1 and HR2, which are heptad repeat regions. Studies have shown that S1 domain induced IgG and IgA antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID‑19 vaccines.<ref name="pmid33340022">{{#invoke:cite journal || vauthors = Dai L, Gao GF | title = Viral targets for vaccines against COVID-19 | journal = Nature Reviews. Immunology | volume = 21 | issue = 2 | pages = 73–82 | date = February 2021 | pmid = 33340022 | pmc = 7747004 | doi = 10.1038/s41577-020-00480-0 |issn=1474-1733 }}</ref>

The M protein is the viral protein responsible for the transmembrane transport of nutrients. It is the cause of the bud release and the formation of the viral envelope.<ref name="Boopathi-2020">{{#invoke:cite journal || vauthors = Boopathi S, Poma AB, Kolandaivel P | title = Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment | journal = Journal of Biomolecular Structure & Dynamics | pages = 3409–3418 | date = April 2020 | volume = 39 | issue = 9 | pmid = 32306836 | pmc = 7196923 | doi = 10.1080/07391102.2020.1758788 }}</ref> The N and E protein are accessory proteins that interfere with the host's immune response.<ref name="Boopathi-2020" />

==== Host factors ====
Human angiotensin converting enzyme 2 (hACE2) is the host factor that SARS-CoV-2 virus targets causing COVID‑19. Theoretically, the usage of [[Chemistry:Angiotensin II receptor blocker|angiotensin receptor blockers]] (ARB) and [[Biology:ACE inhibitor|ACE inhibitor]]s upregulating ACE2 expression might increase morbidity with COVID‑19, though animal data suggest some potential protective effect of ARB; however no clinical studies have proven susceptibility or outcomes. Until further data is available, guidelines and recommendations for hypertensive patients remain.<ref>{{#invoke:cite journal || vauthors = Kai H, Kai M | title = Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19 | journal = Hypertension Research | volume = 43 | issue = 7 | pages = 648–654 | date = July 2020 | pmid = 32341442 | pmc = 7184165 | doi = 10.1038/s41440-020-0455-8 }}</ref>

The effect of the virus on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to a [[Medicine:Systemic inflammatory response syndrome|systemic inflammatory response syndrome]].<ref>{{#invoke:cite journal || vauthors = Chen HX, Chen ZH, Shen HH | title = [Structure of SARS-CoV-2 and treatment of COVID-19] | journal = Sheng Li Xue Bao | volume = 72 | issue = 5 | pages = 617–630 | date = October 2020 | pmid = 33106832 }}</ref>

Among healthy adults not exposed to SARS-CoV-2, about 35% have CD4<sup>+</sup> T cells that recognise the SARS-CoV-2 [[Biology:Peplomer|S protein]] (particularly the S2 subunit) and about 50% react to other proteins of the virus, suggesting [[Biology:Cross-reactivity|cross-reactivity]] from previous [[Medicine:Common cold|common cold]]s caused by other coronaviruses.<ref>{{#invoke:cite journal ||vauthors=Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z |date=4 September 2020 |title=Immunological considerations for COVID-19 vaccine strategies |journal=Nature Reviews Immunology |volume=20 |issue=10 |pages=615–632 |doi=10.1038/s41577-020-00434-6 |pmid=32887954 |pmc=7472682 |issn=1474-1741}}</ref>

It is unknown whether different persons use similar antibody genes in response to COVID‑19.<ref>{{#invoke:cite journal || vauthors = Zhang Q, Ju B, Ge J, Chan JF, Cheng L, Wang R, Huang W, Fang M, Chen P, Zhou B, Song S, Shan S, Yan B, Zhang S, Ge X, Yu J, Zhao J, Wang H, Liu L, Lv Q, Fu L, Shi X, Yuen KY, Liu L, Wang Y, Chen Z, Zhang L, Wang X, Zhang Z | display-authors = 6 | title = Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2 | journal = Nature Communications | volume = 12 | issue = 1 | pages = 4210 | date = July 2021 | pmid = 34244522 | pmc = 8270942 | doi = 10.1038/s41467-021-24514-w | bibcode = 2021NatCo..12.4210Z | s2cid = 235786394 }}</ref>

=== Host cytokine response ===
[[File:Ijms-21-05932-g004.webp|thumb|Mild versus severe [[Biology:Immune system|immune response]] during virus infection]]

The severity of the inflammation can be attributed to the severity of what is known as the [[Medicine:Cytokine storm|cytokine storm]].<ref name="pmid32474885">{{#invoke:cite journal || vauthors = Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S | title = Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment | journal = Clinical Rheumatology | volume = 39 | issue = 7 | pages = 2085–2094 | date = July 2020 | pmid = 32474885 | pmc = 7260446 | doi = 10.1007/s10067-020-05190-5 }}</ref> Levels of interleukin{{spaces}}1B, [[Biology:Interferon gamma|interferon-gamma]], interferon-inducible protein 10, and monocyte chemoattractant protein{{spaces}}1 were all associated with COVID‑19 disease severity. Treatment has been proposed to combat the cytokine storm as it remains to be one of the leading causes of morbidity and mortality in COVID‑19 disease.<ref>{{#invoke:cite journal || vauthors = Quirch M, Lee J, Rehman S | title = Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review | journal = Journal of Medical Internet Research | volume = 22 | issue = 8 | pages = e20193 | date = August 2020 | pmid = 32707537 | pmc = 7428145 | doi = 10.2196/20193 |doi-access=free}}</ref>

A cytokine storm is due to an acute hyperinflammatory response that is responsible for clinical illness in an array of diseases but in COVID‑19, it is related to worse prognosis and increased fatality. The storm causes acute respiratory distress syndrome, blood clotting events such as strokes, myocardial infarction, [[Medicine:Encephalitis|encephalitis]], [[Medicine:Acute kidney injury|acute kidney injury]], and [[Medicine:Vasculitis|vasculitis]]. The production of IL-1, [[Biology:Interleukin 2|IL-2]], IL-6, [[Biology:Tumor necrosis factor|TNF-alpha]], and [[Biology:Interferon gamma|interferon-gamma]], all crucial components of normal immune responses, inadvertently become the causes of a cytokine storm. The cells of the [[Biology:Central nervous system|central nervous system]], the [[Biology:Microglia|microglia]], [[Biology:Neuron|neuron]]s, and [[Biology:Astrocyte|astrocyte]]s, are also involved in the release of pro-inflammatory cytokines affecting the nervous system, and effects of cytokine storms toward the [[Biology:Central nervous system|CNS]] are not uncommon.<ref>{{#invoke:cite journal || vauthors = Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS, Rajagopal S, Pai AR, Kutty S | display-authors = 6 | title = Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper | journal = Frontiers in Immunology | volume = 11 | pages = 1648 | year = 2020 | pmid = 32754159 | pmc = 7365905 | doi = 10.3389/fimmu.2020.01648 | doi-access = free | title-link = doi }}</ref>

=== Pregnancy response ===

There are many unknowns for pregnant women during the COVID-19 pandemic. Given that they are prone to have complications and severe disease infection with other types of coronaviruses, they have been identified as a vulnerable group and advised to take supplementary preventive measures.<ref name="Wastnedge_2021">{{#invoke:cite journal||vauthors=Wastnedge EA, Reynolds RM, van Boeckel SR, Stock SJ, Denison FC, Maybin JA, Critchley HO | display-authors = 6 |date=January 2021|title=Pregnancy and COVID-19|journal=Physiological Reviews|volume=101|issue=1|pages=303–318|doi=10.1152/physrev.00024.2020|pmc=7686875|pmid=32969772}}</ref>

Physiological responses to pregnancy can include:
* Immunological: The immunological response to COVID-19, like other viruses, depends on a working immune system. It adapts during pregnancy to allow the development of the foetus whose genetic load is only partially shared with their mother, leading to a different immunological reaction to infections during the course of pregnancy.<ref name="Wastnedge_2021" />
* Respiratory: Many factors can make pregnant women more vulnerable to hard respiratory infections. One of them is the total reduction of the lungs' capacity and inability to clear secretions.<ref name="Wastnedge_2021" />
* Coagulation: During pregnancy, there are higher levels of circulating coagulation factors, and the pathogenesis of SARS-CoV-2 infection can be implicated. The thromboembolic events with associated mortality are a risk for pregnant women.<ref name="Wastnedge_2021" />

However, from the evidence base, it is difficult to conclude whether pregnant women are at increased risk of grave consequences of this virus.<ref name="Wastnedge_2021" />

In addition to the above, other clinical studies have proved that SARS-CoV-2 can affect the period of pregnancy in different ways. On the one hand, there is little evidence of its impact up to 12 weeks gestation. On the other hand, COVID-19 infection may cause increased rates of unfavourable outcomes in the course of the pregnancy. Some examples of these could be foetal growth restriction, preterm birth, and perinatal mortality, which refers to the foetal death past 22 or 28 completed weeks of pregnancy as well as the death among live-born children up to seven completed days of life.<ref name="Wastnedge_2021" /> For preterm birth, a 2023 review indicates that there appears to be a correlation with COVID-19.<ref>{{#invoke:cite journal ||last1=Digby |first1=Alyson M. |last2=Dahan |first2=Michael H. |title=Obstetrical and gynecologic implications of COVID-19: what have we learned over the first two years of the pandemic |journal=Archives of Gynecology and Obstetrics |date=12 January 2023 |volume=308 |issue=3 |pages=813–819 |doi=10.1007/s00404-022-06847-z|pmid=36633677 |pmc=9838509 }}</ref>

Unvaccinated women in later stages of pregnancy with COVID-19 are more likely than other patients to need very intensive care. Babies born to mothers with COVID-19 are more likely to have breathing problems. Pregnant women are strongly encouraged to get [[Medicine:COVID-19 vaccine|vaccinated]].<ref>{{#invoke:Cite web|| vauthors = Campbell D | title=One in six most critically ill NHS Covid patients are unvaccinated pregnant women | website=The Guardian | date=10 October 2021 | url=https://www.theguardian.com/lifeandstyle/2021/oct/11/one-in-six-most-critically-ill-patients-are-unvaccinated-pregnant-women-with-covid | access-date=25 January 2022 }}</ref>

== Diagnosis ==

COVID‑19 can provisionally be diagnosed on the basis of symptoms and confirmed using [[Biology:Reverse transcription polymerase chain reaction|reverse transcription polymerase chain reaction]] (RT-PCR) or other [[Medicine:Nucleic acid test|nucleic acid]] testing of infected secretions.<ref name="pmid32621814">{{#invoke:cite journal || vauthors = Li C, Zhao C, Bao J, Tang B, Wang Y, Gu B | title = Laboratory diagnosis of coronavirus disease-2019 (COVID-19) | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 510 | pages = 35–46 | date = November 2020 | pmid = 32621814 | pmc = 7329657 | doi = 10.1016/j.cca.2020.06.045 }}</ref><ref name="jTxKm">{{#invoke:cite journal || vauthors = Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, Tao Q, Sun Z, Xia L | display-authors = 6 | title = Correlation of Chest CT and RT-PCR Testing for Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases | journal = Radiology | volume = 296 | issue = 2 | pages = E32–E40 | date = August 2020 | pmid = 32101510 | pmc = 7233399 | doi = 10.1148/radiol.2020200642 }}</ref> Along with laboratory testing, chest CT scans may be helpful to diagnose COVID‑19 in individuals with a high clinical suspicion of infection.<ref name="Salehi-2020">{{#invoke:cite journal || vauthors = Salehi S, Abedi A, Balakrishnan S, Gholamrezanezhad A | title = Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients | journal = AJR. American Journal of Roentgenology | volume = 215 | issue = 1 | pages = 87–93 | date = July 2020 | pmid = 32174129 | doi = 10.2214/AJR.20.23034 | doi-access = free | title-link = doi }}</ref> Detection of a past infection is possible with [[Biology:Serology|serological tests]], which detect [[Biology:Antibody|antibodies]] produced by the body in response to the infection.<ref name="pmid32621814" />

=== Viral testing ===
[[File:Infektionsschutzzentrum im Rautenstrauch-Joest-Museum, Köln-6313 (cropped).jpg|thumb|Demonstration of a [[Nasopharyngeal swab|nasopharyngeal swab]] for COVID‑19 testing]]

The standard methods of testing for presence of SARS-CoV-2 are [[Medicine:Nucleic acid test|nucleic acid test]]s,<ref name="pmid32621814" /><ref name="20200130cdc">{{#invoke:Cite web||date=30 January 2020|title=2019 Novel Coronavirus (2019-nCoV) Situation Summary|url=https://www.cdc.gov/coronavirus/2019-ncov/summary.html|url-status=live|archive-url=https://web.archive.org/web/20200126210549/https://www.cdc.gov/coronavirus/2019-nCoV/summary.html|archive-date=26 January 2020|access-date=30 January 2020|website=U.S. Centers for Disease Control and Prevention (CDC)}}</ref> which detects the presence of viral RNA fragments.<ref name="WHO_InterimGuidance">{{#invoke:Cite web||title=Coronavirus disease (COVID-19) technical guidance: Laboratory testing for 2019-nCoV in humans |work=[[Organization:World Health Organization|World Health Organization]] (WHO) |url=https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/laboratory-guidance |access-date=14 March 2020 |archive-url=https://web.archive.org/web/20200315044138/https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/laboratory-guidance |archive-date=15 March 2020 |url-status=live}}</ref> As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited."<ref name="2k0iS">{{#invoke:cite journal ||vauthors=Bullard J, Dust K, Funk D, Strong JE, Alexander D, Garnett L, Boodman C, Bello A, Hedley A, Schiffman Z, Doan K, Bastien N, Li Y, Van Caeseele PG, Poliquin G |display-authors=6 |title=Predicting Infectious Severe Acute Respiratory Syndrome Coronavirus 2 From Diagnostic Samples |journal=Clinical Infectious Diseases |volume=71 |issue=10 |pages=2663–2666 |date=December 2020 |pmid=32442256 |pmc=7314198 |doi=10.1093/cid/ciaa638 |doi-access=free |title-link=doi}}</ref> The test is typically done on respiratory samples obtained by a [[Nasopharyngeal swab|nasopharyngeal swab]]; however, a nasal swab or sputum sample may also be used.<ref name="CDC2020Testing">{{#invoke:Cite web||date=11 February 2020|title=Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19) |url=https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html|url-status=live|archive-url=https://web.archive.org/web/20200304165907/https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html|archive-date=4 March 2020|access-date=26 March 2020|website=U.S. Centers for Disease Control and Prevention (CDC)}}</ref><ref name="20200129cdc">{{#invoke:Cite web||date=29 January 2020|title=Real-Time RT-PCR Panel for Detection 2019-nCoV |url=https://www.cdc.gov/coronavirus/2019-ncov/lab/rt-pcr-detection-instructions.html|url-status=live|archive-url=https://web.archive.org/web/20200130202031/https://www.cdc.gov/coronavirus/2019-ncov/lab/rt-pcr-detection-instructions.html|archive-date=30 January 2020|access-date=1 February 2020|website=U.S. Centers for Disease Control and Prevention (CDC)}}</ref> Results are generally available within hours.<ref name="pmid32621814" /> The WHO has published several testing protocols for the disease.<ref>{{#invoke:Cite web||title=Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases|url=https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117|url-status=live|archive-url=https://web.archive.org/web/20200317023052/https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117|archive-date=17 March 2020|access-date=13 March 2020|website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref>

Several laboratories and companies have developed serological tests, which detect antibodies produced by the body in response to infection. Several have been evaluated by [[Organization:Public Health England|Public Health England]] and approved for use in the UK.<ref name="independent9515466">{{#invoke:cite news||date=14 May 2020|title=NHS staff will be first to get new coronavirus antibody test, medical chief promises|website=The Independent|url=https://www.independent.co.uk/news/uk/home-news/coronavirus-test-antibody-covid-roche-immune-nhs-staff-a9515466.html|access-date=14 May 2020}}</ref>

The [[Organization:University of Oxford|University of Oxford]]'s CEBM has pointed to mounting evidence<ref name="yFMEP">{{#invoke:Cite web|| vauthors = Heneghan C, Jefferson T |date=1 September 2020|title=Virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR|url=https://www.cebm.net/study/virological-characterization-of-covid-19-patients-that-test-re-positive-for-sars-cov-2-by-rt-pcr|access-date=19 September 2020|website=CEBM}}</ref><ref name="2exX5">{{#invoke:cite journal || vauthors = Lu J, Peng J, Xiong Q, Liu Z, Lin H, Tan X, Kang M, Yuan R, Zeng L, Zhou P, Liang C, Yi L, du Plessis L, Song T, Ma W, Sun J, Pybus OG, Ke C | display-authors = 6 | title = Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR | journal = eBioMedicine | volume = 59 | pages = 102960 | date = September 2020 | pmid = 32853988 | pmc = 7444471 | doi = 10.1016/j.ebiom.2020.102960 }}</ref> that "a good proportion of 'new' mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with" and have called for "an international effort to standardize and periodically calibrate testing"<ref name="PQGAv">{{#invoke:Cite web|| vauthors = Spencer E, Jefferson T, Brassey J, Heneghan C |date=11 September 2020|title=When is Covid, Covid?|url=https://www.cebm.net/covid-19/when-is-covid-covid/|access-date=19 September 2020|website=The Centre for Evidence-Based Medicine}}</ref> In September 2020, the UK government issued "guidance for procedures to be implemented in laboratories to provide assurance of positive SARS-CoV-2 RNA results during periods of low prevalence, when there is a reduction in the predictive value of positive test results".<ref name="9Kblp">{{#invoke:Cite web||title=SARS-CoV-2 RNA testing: assurance of positive results during periods of low prevalence |url=https://www.gov.uk/government/publications/sars-cov-2-rna-testing-assurance-of-positive-results-during-periods-of-low-prevalence|access-date=19 September 2020|website=GOV.UK}}</ref>

=== Imaging ===
<noinclude>[[File:COVID19CTPneumonia.jpg|thumb|A CT scan of a person with COVID-19 shows lesions (bright regions) in the lungs]]</noinclude>
[[File:COVID19CT1.webp|thumb|CT scan of rapid progression stage of COVID-19]]
[[File:COVID-19 Pneumonie - 82m Roe Thorax ap - 001.jpg|thumb|Chest X-ray showing COVID‑19 pneumonia]]

Chest CT scans may be helpful to diagnose COVID‑19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening.<ref name="Salehi-2020" /><ref name="acr.org">{{#invoke:Cite web||date=22 March 2020|title=ACR Recommendations for the use of Chest Radiography and Computed Tomography (CT) for Suspected COVID-19 Infection|url=https://www.acr.org/Advocacy-and-Economics/ACR-Position-Statements/Recommendations-for-Chest-Radiography-and-CT-for-Suspected-COVID19-Infection|url-status=live|archive-url=https://web.archive.org/web/20200328055813/https://www.acr.org/Advocacy-and-Economics/ACR-Position-Statements/Recommendations-for-Chest-Radiography-and-CT-for-Suspected-COVID19-Infection|archive-date=28 March 2020|website=American College of Radiology}}</ref> Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection.<ref name="Salehi-2020" /><ref>{{#invoke:cite journal || vauthors = Pormohammad A, Ghorbani S, Khatami A, Razizadeh MH, Alborzi E, Zarei M, Idrovo JP, Turner RJ | display-authors = 6 | title = Comparison of influenza type A and B with COVID-19: A global systematic review and meta-analysis on clinical, laboratory and radiographic findings | journal = Reviews in Medical Virology | pages = e2179 | date = October 2020 | pmid = 33035373 | pmc = 7646051 | doi = 10.1002/rmv.2179 | s2cid = 222255245 | title-link = doi | volume = 31 | issue = 3 | doi-access = free }}</ref> Subpleural dominance, [[Medicine:Crazy paving|crazy paving]] (lobular septal thickening with variable alveolar filling), and [[Medicine:Pulmonary consolidation|consolidation]] may appear as the disease progresses.<ref name="Salehi-2020" /><ref>{{#invoke:cite journal || vauthors = Lee EY, Ng MY, Khong PL | title = COVID-19 pneumonia: what has CT taught us? | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 4 | pages = 384–385 | date = April 2020 | pmid = 32105641 | pmc = 7128449 | doi = 10.1016/S1473-3099(20)30134-1 | title-link = doi | doi-access = free }}</ref> Characteristic imaging features on chest radiographs and computed tomography (CT) of people who are symptomatic include asymmetric peripheral ground-glass opacities without pleural effusions.<ref name="AJR">{{#invoke:cite journal || vauthors = Li Y, Xia L | title = Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management | journal = AJR. American Journal of Roentgenology | volume = 214 | issue = 6 | pages = 1280–1286 | date = June 2020 | pmid = 32130038 | doi = 10.2214/AJR.20.22954 | s2cid = 212416282 }}</ref>

Many groups have created COVID‑19 datasets that include imagery such as the [[Organization:Italian Society of Medical and Interventional Radiology|Italian Radiological Society]] which has compiled an international online database of imaging findings for confirmed cases.<ref name="Cx70C">{{#invoke:Cite web||title=COVID-19 Database |url=https://www.sirm.org/category/senza-categoria/covid-19/ |website=Società Italiana di Radiologia Medica e Interventistica |access-date=11 March 2020 |language=it}}</ref> Due to overlap with other infections such as adenovirus, imaging without confirmation by rRT-PCR is of limited specificity in identifying COVID‑19.<ref name="AJR" /> A large study in China compared chest CT results to PCR and demonstrated that though imaging is less specific for the infection, it is faster and more sensitive.<ref name="jTxKm" />

=== Coding ===
In late 2019, the WHO assigned emergency [[Medicine:ICD-10|ICD-10]] disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection and U07.2 for deaths from clinically or epidemiologically diagnosed COVID‑19 without lab-confirmed SARS-CoV-2 infection.<ref name="ICD10_2019_U07p2">{{#invoke:Cite web||year=2019|title=ICD-10 Version:2019|website=[[Organization:World Health Organization|World Health Organization]] (WHO) |url=https://icd.who.int/browse10/2019/en#/U07.1|access-date=31 March 2020 |url-status=live|archive-url=https://archive.today/20200331004754/https://icd.who.int/browse10/2019/en%23/U07.1|archive-date=31 March 2020|quote=U07.2{{snd}}COVID-19, virus not identified{{snd}}COVID-19 NOS{{snd}}Use this code when COVID-19 is diagnosed clinically or epidemiologically but laboratory testing is inconclusive or not available. Use additional code, if desired, to identify pneumonia or other manifestations}}</ref>

=== Pathology ===
The main pathological findings at autopsy are:
* [[Physics:Macroscopic scale|Macroscopy]]: [[Medicine:Pericarditis|pericarditis]], lung consolidation and [[Medicine:Pulmonary edema|pulmonary oedema]]<ref name="Cureus" />
* Lung findings:
** minor serous [[Biology:Exudate|exudation]], minor [[Biology:Fibrin|fibrin]] exudation<ref name="Cureus" />
** pulmonary oedema, pneumocyte [[Medicine:Hyperplasia|hyperplasia]], large atypical pneumocytes, interstitial [[Medicine:Inflammation|inflammation]] with lymphocytic [[Medicine:Infiltration (medical)|infiltration]] and [[Biology:Giant cell|multinucleated giant cell]] formation<ref name="Cureus" />
** [[Medicine:Diffuse alveolar damage|diffuse alveolar damage]] (DAD) with diffuse alveolar exudates. DAD is the cause of [[Medicine:Acute respiratory distress syndrome|acute respiratory distress syndrome]] (ARDS) and severe [[Medicine:Hypoxemia|hypoxaemia]].<ref name="Cureus" />
** [[Biology:Healing|organisation]] of [[Biology:Exudate|exudate]]s in alveolar cavities and [[Medicine:Pulmonary fibrosis|pulmonary interstitial fibrosis]]<ref name="Cureus" />
** [[Biology:Plasma cell|plasmocytosis]] in [[Medicine:Bronchoalveolar lavage|bronchoalveolar lavage]] (BAL)<ref>{{#invoke:cite journal || vauthors = Giani M, Seminati D, Lucchini A, Foti G, Pagni F | title = Exuberant Plasmocytosis in Bronchoalveolar Lavage Specimen of the First Patient Requiring Extracorporeal Membrane Oxygenation for SARS-CoV-2 in Europe | journal = Journal of Thoracic Oncology | volume = 15 | issue = 5 | pages = e65–e66 | date = May 2020 | pmid = 32194247 | pmc = 7118681 | doi = 10.1016/j.jtho.2020.03.008 }}</ref>
* Blood and vessels: [[Medicine:Disseminated intravascular coagulation|disseminated intravascular coagulation]] (DIC);<ref>{{#invoke:cite journal || vauthors = Lillicrap D | title = Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia | journal = Journal of Thrombosis and Haemostasis | volume = 18 | issue = 4 | pages = 786–787 | date = April 2020 | pmid = 32212240 | pmc = 7166410 | doi = 10.1111/jth.14781 }}</ref> leukoerythroblastic reaction,<ref>{{#invoke:cite journal || vauthors = Mitra A, Dwyre DM, Schivo M, Thompson GR, Cohen SH, Ku N, Graff JP | display-authors = 6 | title = Leukoerythroblastic reaction in a patient with COVID-19 infection | journal = American Journal of Hematology | volume = 95 | issue = 8 | pages = 999–1000 | date = August 2020 | pmid = 32212392 | pmc = 7228283 | doi = 10.1002/ajh.25793 | title-link = doi | doi-access = free }}</ref> [[Medicine:Endotheliitis|endotheliitis]],<ref name="SatturwarFowkes2021">{{#invoke:cite journal || vauthors = Satturwar S, Fowkes M, Farver C, Wilson AM, Eccher A, Girolami I, Pujadas E, Bryce C, Salem F, El Jamal SM, Paniz-Mondolfi A, Petersen B, Gordon RE, Reidy J, Fraggetta F, Marshall DA, Pantanowitz L | display-authors = 6 | title = Postmortem Findings Associated With SARS-CoV-2: Systematic Review and Meta-analysis | journal = The American Journal of Surgical Pathology | volume = 45 | issue = 5 | pages = 587–603 | date = May 2021 | pmid = 33481385 | doi = 10.1097/PAS.0000000000001650 | pmc = 8132567 | s2cid = 231679276 }}</ref> [[Medicine:Hemophagocytosis|hemophagocytosis]]<ref name="SatturwarFowkes2021" />
* Heart: [[Biology:Cardiac muscle cell|cardiac muscle cell]] necrosis<ref name="SatturwarFowkes2021" />
* Liver: microvesicular [[Medicine:Steatosis|steatosis]]<ref name="Cureus" />
* Nose: shedding of olfactory epithelium<ref name="Meunier-2020" />
* Brain: [[Medicine:Cerebral infarction|infarction]]<ref name="SatturwarFowkes2021" />
* Kidneys: acute tubular damage.<ref name="SatturwarFowkes2021" />
* Spleen: white pulp depletion.<ref name="SatturwarFowkes2021" />

== Prevention ==
<noinclude>
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</noinclude>
[[File:20200609 Effect of pandemic containment measures.gif|thumb|upright=1|Without pandemic containment measures{{snd}}such as social distancing, vaccination, and face masks{{snd}}pathogens can spread exponentially.<ref name=Science_20200515>{{#invoke:cite journal || vauthors = Maier BF, Brockmann D | title = Effective containment explains subexponential growth in recent confirmed COVID-19 cases in China | journal = Science | volume = 368 | issue = 6492 | pages = 742–746 | date = May 2020 | pmid = 32269067 | pmc = 7164388 | doi = 10.1126/science.abb4557| arxiv=2002.07572 | title-link = doi | doi-access = free | bibcode = 2020Sci...368..742M }} ("...{{spaces}}initial exponential growth expected for an unconstrained outbreak.")</ref> This graphic shows how early adoption of containment measures tends to protect wider swaths of the population.]]

Preventive measures to reduce the chances of infection include getting vaccinated, staying at home, wearing a mask in public, avoiding crowded places, keeping distance from others, ventilating indoor spaces, managing potential exposure durations,<ref>{{#invoke:Cite web||url=https://reallycorrect.com/ReallyCorrectWp1/covid-19-safety-information-ideas/#Viral-Load-Exposure-Factors|title=Viral Load Exposure Factors|website=ReallyCorrect.com}}</ref> washing hands with soap and water often and for at least twenty seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.<ref name="CDC042020">{{#invoke:Cite web||date=28 June 2020|title=Recommendation Regarding the Use of Cloth Face Coverings, Especially in Areas of Significant Community-Based Transmission|work=U.S. Centers for Disease Control and Prevention (CDC) |url=https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover.html}}</ref><ref>{{#invoke:Cite web||title=Scientific Brief: SARS-CoV-2 and Potential Airborne Transmission |url=https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-sars-cov-2.html |website=COVID-19 Published Science and Research |date=11 February 2020 |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=30 October 2020}}</ref>

Those diagnosed with COVID‑19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items.<ref name="CDC2020IfSick">{{#invoke:Cite web||date=5 April 2020|title=What to Do if You Are Sick|url=https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/steps-when-sick.html|url-status=live|archive-url=https://web.archive.org/web/20200214153016/https://www.cdc.gov/coronavirus/2019-ncov/about/steps-when-sick.html|archive-date=14 February 2020|access-date=24 April 2020|website=U.S. Centers for Disease Control and Prevention (CDC)|vauthors=((Centers for Disease Control and Prevention))}}</ref><ref>{{#invoke:Cite web||date=10 March 2020|title=Coronavirus Disease 2019 (COVID-19) – Prevention & Treatment |url=https://www.cdc.gov/coronavirus/2019-ncov/about/prevention.html|url-status=live|archive-url=https://web.archive.org/web/20200311163637/https://www.cdc.gov/coronavirus/2019-ncov/about/prevention.html|archive-date=11 March 2020|access-date=11 March 2020|work=U.S. Centers for Disease Control and Prevention (CDC)}}</ref>

The first COVID‑19 vaccine was granted regulatory approval on 2{{spaces}}December 2020 by the UK medicines regulator [[Organization:Medicines and Healthcare products Regulatory Agency|MHRA]].<ref name="ukgov12-2">{{#invoke:Cite web||title=UK medicines regulator gives approval for first UK COVID-19 vaccine |url=https://www.gov.uk/government/news/uk-medicines-regulator-gives-approval-for-first-uk-covid-19-vaccine |publisher=Medicines and Healthcare Products Regulatory Agency, Government of the UK |access-date=2 December 2020 |date=2 December 2020}}</ref> It was evaluated for emergency use authorisation (EUA) status by the US FDA, and in several other countries.<ref name="mueller">{{#invoke:cite news || vauthors = Mueller B |title=U.K. Approves Pfizer Coronavirus Vaccine, a First in the West |url=https://www.nytimes.com/2020/12/02/world/europe/pfizer-coronavirus-vaccine-approved-uk.html |archive-url=https://web.archive.org/web/20201202071559/https://www.nytimes.com/2020/12/02/world/europe/pfizer-coronavirus-vaccine-approved-uk.html |archive-date=2 December 2020 |url-access=subscription |url-status=live |access-date=2 December 2020 |work=The New York Times |date=2 December 2020}}</ref> Initially, the US [[Organization:National Institutes of Health|National Institutes of Health]] guidelines do not recommend any medication for prevention of COVID‑19, before or after exposure to the SARS-CoV-2 virus, outside the setting of a clinical trial.<ref name="NIHGuidelines2020">{{#invoke:Cite web||title=COVID-19 Treatment Guidelines |url=https://covid19treatmentguidelines.nih.gov/introduction/ |website=nih.gov |publisher=National Institutes of Health |access-date=21 April 2020}}</ref><ref name="Sanders202022" /> Without a vaccine, other prophylactic measures, or effective treatments, a key part of managing COVID‑19 is trying to decrease and delay the epidemic peak, known as "flattening the [[Epidemic curve|curve]]".<ref name="Lancet2020Flatten">{{#invoke:cite journal || vauthors = Anderson RM, Heesterbeek H, Klinkenberg D, Hollingsworth TD | title = How will country-based mitigation measures influence the course of the COVID-19 epidemic? | journal = Lancet | volume = 395 | issue = 10228 | pages = 931–934 | date = March 2020 | pmid = 32164834 | pmc = 7158572 | doi = 10.1016/S0140-6736(20)30567-5 | quote = A key issue for epidemiologists is helping policy makers decide the main objectives of mitigation{{snd}}e.g. minimising morbidity and associated mortality, avoiding an epidemic peak that overwhelms health-care services, keeping the effects on the economy within manageable levels, and flattening the epidemic curve to wait for vaccine development and manufacture on scale and antiviral drug therapies. | doi-access = free | title-link = doi }}</ref> This is done by slowing the infection rate to decrease the risk of health services being overwhelmed, allowing for better treatment of active cases, and delaying additional cases until effective treatments or a vaccine become available.<ref name="Lancet2020Flatten" /><ref name="Wiles">{{#invoke:Cite web|| vauthors = Wiles S |title=After 'Flatten the Curve', we must now 'Stop the Spread'. Here's what that means |url=https://thespinoff.co.nz/society/14-03-2020/after-flatten-the-curve-we-must-now-stop-the-spread-heres-what-that-means/ |website=The Spinoff |access-date=13 March 2020 |date=14 March 2020 |archive-url=https://web.archive.org/web/20200326232315/https://thespinoff.co.nz/society/14-03-2020/after-flatten-the-curve-we-must-now-stop-the-spread-heres-what-that-means/ |archive-date=26 March 2020 |url-status=live}}</ref>

=== Vaccine ===
{{Main|Medicine:COVID-19 vaccine}}
[[File:Fphar-11-00937-g004-L.jpg|thumb|Different vaccine candidate types in development for SARS-CoV-2]]
[[File:2021- COVID-19 death rates by vaccination status - US.svg|thumb|Death rates for unvaccinated Americans substantially exceeded those who were vaccinated, with bivalent boosters further reducing the death rate.<ref name=COVIDmortality_2021_2023>{{cite web |title=Data on COVID-19 mortality by vaccination status |url=https://ourworldindata.org/covid-deaths-by-vaccination |publisher=Our World in Data (CDC data) |archive-url=https://web.archive.org/web/20231016112249/https://ourworldindata.org/covid-deaths-by-vaccination |archive-date=16 October 2023 |date=April 2023 |quote=Data source: Centers for Disease Control and Prevention, Vaccine Breakthrough/Surveillance and Analytics Team. |url-status=live }}</ref>]]
<!-- TO EDIT THIS SECTION, GO TO [[Medicine:COVID-19 vaccine|COVID-19 vaccine]]. -->
{{Excerpt|COVID-19 vaccine|hat=no|paragraphs=4-7}}

=== Face masks and respiratory hygiene ===
[[File:2009Julija-210.jpg|thumb|Masks with an exhalation valve. The valves are a weak point that can transmit the viruses outwards.]]

{{Excerpt|Face masks during the COVID-19 pandemic|hat=no|paragraphs=2-4}}

=== Indoor ventilation and avoiding crowded indoor spaces ===
The CDC states that avoiding crowded indoor spaces reduces the risk of COVID-19 infection.<ref name="CDC-2020b">{{#invoke:Cite web||last=CDC|date=11 February 2020|title=Scientific Brief: SARS-CoV-2 Transmission|url=https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/sars-cov-2-transmission.html|access-date=10 May 2021|website=U.S. Centers for Disease Control and Prevention (CDC) }}</ref> When indoors, increasing the rate of air change, decreasing recirculation of air and increasing the use of outdoor air can reduce transmission.<ref name="CDC-2020b" /><ref name="ecdc_transmission2">{{#invoke:Cite web||date=7 September 2020|title=Transmission of COVID-19 |url=https://www.ecdc.europa.eu/en/covid-19/latest-evidence/transmission|access-date=14 October 2020|publisher=[[Organization:European Centre for Disease Prevention and Control|European Centre for Disease Prevention and Control]]}}</ref> The WHO recommends [[Physics:Ventilation (architecture)|ventilation]] and air filtration in public spaces to help clear out infectious aerosols.<ref name="CDCasof07092020" /><ref name="KoFZO">{{#invoke:cite AV media ||date=30 October 2020 |url=https://www.youtube.com/watch?v=XJC1f7F4qtc |title=WHO's Science in 5 on COVID-19 – Ventilation – 30 October 2020 |publisher=World Health Organization (WHO) |via=[[Company:YouTube|YouTube]] |access-date=8 December 2022 |archive-url=https://web.archive.org/web/20221025043909/http://www.youtube.com/watch?v=XJC1f7F4qtc |archive-date=25 October 2022 |url-status=live}}</ref><ref name="Lancetdroplet05272020">{{#invoke:cite journal||vauthors=Somsen GA, van Rijn C, Kooij S, Bem RA, Bonn D|date=July 2020|title=Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission|journal=The Lancet. Respiratory Medicine|publisher=Elsesier|volume=8|issue=7|pages=658–659 |doi=10.1016/S2213-2600(20)30245-9|pmc=7255254|pmid=32473123}}</ref>

Exhaled respiratory particles can build-up within enclosed spaces with inadequate [[Physics:Ventilation (architecture)|ventilation]]. The risk of COVID‑19 infection increases especially in spaces where people engage in physical exertion or raise their voice (e.g., exercising, shouting, singing) as this increases exhalation of respiratory droplets. Prolonged exposure to these conditions, typically more than 15 minutes, leads to higher risk of infection.<ref name="CDC-2020b" />

[[Engineering:Displacement ventilation|Displacement ventilation]] with large natural inlets can move stale air directly to the exhaust in [[Physics:Laminar flow|laminar flow]] while significantly reducing the concentration of droplets and particles. [[Physics:Passive ventilation|Passive ventilation]] reduces energy consumption and maintenance costs but may lack [[Engineering:Demand controlled ventilation|controllability]] and [[Physics:Heat recovery ventilation|heat recovery]]. Displacement ventilation can also be achieved mechanically with higher energy and maintenance costs. The use of large ducts and openings helps to prevent mixing in closed environments. Recirculation and mixing should be avoided because recirculation prevents dilution of harmful particles and redistributes possibly contaminated air, and mixing increases the concentration and range of infectious particles and keeps larger particles in the air.<ref>{{#invoke:cite journal ||vauthors=Lipinski T, Ahmad D, Serey N, Jouhara H |date=1 November 2020 |title=Review of ventilation strategies to reduce the risk of disease transmission in high occupancy buildings |url=https://www.sciencedirect.com/science/article/pii/S266620272030032X |journal=International Journal of Thermofluids |volume=7–8 |pages=100045 |doi=10.1016/j.ijft.2020.100045 |s2cid=221642242 |issn=2666-2027}}</ref>

=== Hand-washing and hygiene ===
[[File:In Rwanda build where everyone can wash hand in prevention of covid-19.jpg|thumb|Students in [[Biology:Rwanda|Rwanda]] hand washing and wearing face masks during the COVID‑19 pandemic in the country.]]
Thorough hand hygiene after any cough or sneeze is required.<ref name="nhs.uk-2020">{{#invoke:Cite web||date=2 June 2020|title=Social distancing: what you need to do – Coronavirus (COVID-19) |url=https://www.nhs.uk/conditions/coronavirus-covid-19/social-distancing/what-you-need-to-do/|access-date=18 August 2020|website=nhs.uk}}</ref> The WHO also recommends that individuals wash hands often with soap and water for at least twenty seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose.<ref name="WHO-2020b">{{#invoke:Cite web||title=Advice for the public on COVID-19 – World Health Organization|url=https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public|access-date=18 August 2020|website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref> When soap and water are not available, the CDC recommends using an alcohol-based hand sanitiser with at least 60% alcohol.<ref>{{#invoke:Cite web||date=11 February 2020|title=COVID-19 and Your Health|url=https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/hand-sanitizer.html|access-date=23 March 2021|website=U.S. Centers for Disease Control and Prevention (CDC)|quote=To prevent the spread of germs, including COVID-19, CDC recommends washing hands with soap and water whenever possible because it reduces the amount of many types of germs and chemicals on hands. But if soap and water are not readily available, using a hand sanitizer with at least 60% alcohol can help you avoid getting sick and spreading germs to others.}}</ref> For areas where commercial hand sanitisers are not readily available, the WHO provides two formulations for local production. In these formulations, the antimicrobial activity arises from [[Chemistry:Ethanol|ethanol]] or isopropanol. [[Chemistry:Hydrogen peroxide|Hydrogen peroxide]] is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for hand antisepsis." [[Chemistry:Glycerol|Glycerol]] is added as a [[Chemistry:Humectant|humectant]].<ref>{{#invoke:cite book||title=WHO Guidelines on Hand Hygiene in Health Care: First Global Patient Safety Challenge Clean Care Is Safer Care|date=19 March 2009|publisher=[[Organization:World Health Organization|World Health Organization]] (WHO)|chapter=WHO-recommended handrub formulations|access-date=19 March 2020|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK144054/}}</ref>

=== Social distancing ===
Social distancing (also known as physical distancing) includes [[Medicine:Infection control|infection control]] actions intended to slow the spread of the disease by minimising close contact between individuals. Methods include quarantines; travel restrictions; and the closing of schools, workplaces, stadiums, theatres, or shopping centres. Individuals may apply social distancing methods by staying at home, limiting travel, avoiding crowded areas, using no-contact greetings, and physically distancing themselves from others.<ref>{{#invoke:cite journal || vauthors = Nussbaumer-Streit B, Mayr V, Dobrescu AI, Chapman A, Persad E, Klerings I, Wagner G, Siebert U, Ledinger D, Zachariah C, Gartlehner G | display-authors=6 |date=September 2020 |title=Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review |journal=The Cochrane Database of Systematic Reviews |volume=2020 |issue=9 |pages=CD013574 |doi=10.1002/14651858.CD013574.pub2 |issn=1469-493X |pmc=8133397 |pmid=33959956 }}</ref>

In 2020, outbreaks occurred in prisons due to crowding and an inability to enforce adequate social distancing.<ref name="Hawks2020" /><ref>{{#invoke:Cite web|| vauthors = Waldstein D |title=To Fight Virus in Prisons, C.D.C. Suggests More Screenings |website={{wipe|The New York Times}} |date=6 May 2020 |url=https://www.nytimes.com/2020/05/06/health/coronavirus-prisons-cdc.html |archive-url=https://web.archive.org/web/20200507161241/https://www.nytimes.com/2020/05/06/health/coronavirus-prisons-cdc.html |archive-date=7 May 2020 |url-access=subscription |url-status=live |access-date=14 May 2020}}</ref> In the United States, the prisoner population is ageing and many of them are at high risk for poor outcomes from COVID‑19 due to high rates of coexisting heart and lung disease, and poor access to high-quality healthcare.<ref name="Hawks2020">{{#invoke:cite journal || vauthors = Hawks L, Woolhandler S, McCormick D | title = COVID-19 in Prisons and Jails in the United States | journal = JAMA Internal Medicine | volume = 180 | issue = 8 | pages = 1041–1042 | date = August 2020 | pmid = 32343355 | doi = 10.1001/jamainternmed.2020.1856 | doi-access = free | title-link = doi }}</ref>

=== Surface cleaning ===
After being expelled from the body, coronaviruses can survive on surfaces for hours to days. If a person touches the dirty surface, they may deposit the virus at the eyes, nose, or mouth where it can enter the body and cause infection.<ref name="CDCTrans">{{#invoke:Cite web||url=https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html |title=How COVID-19 Spreads |date=18 September 2020 |website=U.S. Centers for Disease Control and Prevention (CDC) |url-status=live |archive-url=https://web.archive.org/web/20200919224920/https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fprepare%2Ftransmission.html |archive-date=19 September 2020 |access-date=20 September 2020}}</ref> Evidence indicates that contact with infected surfaces is not the main driver of COVID‑19,<ref>{{#invoke:cite journal || vauthors = Goldman E | title = Exaggerated risk of transmission of COVID-19 by fomites | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 8 | pages = 892–893 | date = August 2020 | pmid = 32628907 | pmc = 7333993 | doi = 10.1016/S1473-3099(20)30561-2 }}</ref><ref>{{#invoke:Cite web|| vauthors = Weixel N |date=5 April 2021|title=CDC says risk of COVID-19 transmission on surfaces 1 in 10,000|url=https://thehill.com/policy/healthcare/546541-cdc-risk-of-covid-transmission-on-surfaces-is-low|access-date=19 December 2021|website=The Hill}}</ref><ref name="cdc.gov">{{#invoke:Cite web||date=5 April 2021|title=Science Brief: SARS-CoV-2 and Surface (Fomite) Transmission for Indoor Community Environments|url=https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/surface-transmission.html|url-status=live |website=U.S. Centers for Disease Control and Prevention (CDC)|archive-url=https://web.archive.org/web/20210405151126/https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/surface-transmission.html |archive-date=5 April 2021 }}</ref> leading to recommendations for optimised disinfection procedures to avoid issues such as the increase of [[Biology:Antimicrobial resistance|antimicrobial resistance]] through the use of inappropriate cleaning products and processes.<ref name="disinfection-foodindus" /><ref>{{#invoke:cite journal || vauthors = Rezasoltani S, Yadegar A, Hatami B, Asadzadeh Aghdaei H, Zali MR | title = Antimicrobial Resistance as a Hidden Menace Lurking Behind the COVID-19 Outbreak: The Global Impacts of Too Much Hygiene on AMR | journal = Frontiers in Microbiology | volume = 11 | pages = 590683 | year = 2020 | pmid = 33384670 | pmc = 7769770 | doi = 10.3389/fmicb.2020.590683 | doi-access = free | title-link = doi }}</ref> Deep cleaning and other surface sanitation has been criticised as hygiene theatre, giving a false sense of security against something primarily spread through the air.<ref>{{#invoke:Cite web|| vauthors = Thompson D |date=8 February 2021|title=Hygiene Theater Is Still a Huge Waste of Time|url=https://www.theatlantic.com/ideas/archive/2021/02/hygiene-theater-still-waste/617939/|access-date=27 February 2021|website=The Atlantic }}</ref><ref>{{#invoke:Cite web|| vauthors = Thompson D |date=27 July 2020|title=Hygiene Theater Is a Huge Waste of Time |url=https://www.theatlantic.com/ideas/archive/2020/07/scourge-hygiene-theater/614599/|access-date=27 February 2021|website=The Atlantic }}</ref>

The amount of time that the virus can survive depends significantly on the type of surface, the temperature, and the humidity.<ref name="Bueckert-2020">{{#invoke:cite journal || vauthors = Bueckert M, Gupta R, Gupta A, Garg M, Mazumder A | title = Infectivity of SARS-CoV-2 and Other Coronaviruses on Dry Surfaces: Potential for Indirect Transmission | journal = Materials | volume = 13 | issue = 22 | page = 5211 | date = November 2020 | pmid = 33218120 | pmc = 7698891 | doi = 10.3390/ma13225211 | bibcode = 2020Mate...13.5211B | doi-access = free | title-link = doi }}</ref> Coronaviruses die very quickly when exposed to the UV light in [[Astronomy:Sunlight|sunlight]].<ref name="Bueckert-2020" /> Like other enveloped viruses, SARS-CoV-2 survives longest when the temperature is at [[Physics:Room temperature|room temperature]] or lower, and when the [[Physics:Relative humidity|relative humidity]] is low (<50%).<ref name="Bueckert-2020" />

On many surfaces, including glass, some types of plastic, stainless steel, and skin, the virus can remain infective for several days indoors at room temperature, or even about a week under ideal conditions.<ref name="Bueckert-2020" /><ref>{{#invoke:cite journal || vauthors = Bhardwaj R, Agrawal A | title = How coronavirus survives for days on surfaces | journal = Physics of Fluids | volume = 32 | issue = 11 | pages = 111706 | date = November 2020 | pmid = 33281435 | pmc = 7713872 | doi = 10.1063/5.0033306 | bibcode = 2020PhFl...32k1706B }}</ref> On some surfaces, including cotton fabric and copper, the virus usually dies after a few hours.<ref name="Bueckert-2020" /> The virus dies faster on porous surfaces than on non-porous surfaces due to capillary action within pores and faster aerosol droplet evaporation.<ref>{{#invoke:cite journal || vauthors = Chatterjee S, Murallidharan JS, Agrawal A, Bhardwaj R | title = Why coronavirus survives longer on impermeable than porous surfaces | journal = Physics of Fluids | volume = 33 | issue = 2 | pages = 021701 | date = February 2021 | pmid = 33746485 | pmc = 7978145 | doi = 10.1063/5.0037924 | bibcode = 2021PhFl...33b1701C }}</ref><ref name="cdc.gov" /><ref name="Bueckert-2020" /> However, of the many surfaces tested, two with the longest survival times are N95 respirator masks and surgical masks, both of which are considered porous surfaces.<ref name="Bueckert-2020" />

The CDC says that in most situations, cleaning surfaces with soap or detergent, not disinfecting, is enough to reduce risk of transmission.<ref name="CDC-2020a">{{#invoke:Cite web||last=CDC|date=11 February 2020|title=Coronavirus Disease 2019 (COVID-19)|url=https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/surface-transmission.html|access-date=12 April 2021|website=U.S. Centers for Disease Control and Prevention (CDC) }}</ref><ref>{{#invoke:cite news|| vauthors = Anthes E |date=8 April 2021|title=Has the Era of Overzealous Cleaning Finally Come to an End?|work=The New York Times|url=https://www.nytimes.com/2021/04/08/health/coronavirus-hygiene-cleaning-surfaces.html |archive-url=https://ghostarchive.org/archive/20211228/https://www.nytimes.com/2021/04/08/health/coronavirus-hygiene-cleaning-surfaces.html |archive-date=28 December 2021 |url-access=limited|access-date=12 April 2021| url-status=live }}</ref> The CDC recommends that if a COVID‑19 case is suspected or confirmed at a facility such as an office or day care, all areas such as offices, bathrooms, common areas, shared electronic equipment like tablets, touch screens, keyboards, remote controls, and ATMs used by the ill persons should be disinfected.<ref name="sxygw">{{#invoke:Cite web||date=11 February 2020|title=Interim Recommendations for US Community Facilities with Suspected/Confirmed Coronavirus Disease 2019|url=https://www.cdc.gov/coronavirus/2019-ncov/community/organizations/cleaning-disinfection.html|access-date=4 April 2020|publisher=U.S. Centers for Disease Control and Prevention (CDC)}}</ref> Surfaces may be decontaminated with 62–71 per cent [[Chemistry:Ethanol|ethanol]], 50–100 per cent isopropanol, 0.1 per cent [[Chemistry:Sodium hypochlorite|sodium hypochlorite]], 0.5 per cent hydrogen peroxide, 0.2–7.5 per cent [[Chemistry:Povidone-iodine|povidone-iodine]], or 50–200 ppm [[Chemistry:Hypochlorous acid|hypochlorous acid]]. Other solutions, such as [[Chemistry:Benzalkonium chloride|benzalkonium chloride]] and chlorhexidine gluconate, are less effective. [[Physics:Ultraviolet germicidal irradiation|Ultraviolet germicidal irradiation]] may also be used,<ref name="CDCasof07092020">{{#invoke:Cite web||date=9 July 2020|title=COVID-19 Employer Information for Office Buildings|url=https://www.cdc.gov/coronavirus/2019-ncov/community/office-buildings.html|access-date=9 July 2020|website=U.S. Centers for Disease Control and Prevention (CDC)|vauthors=((National Center for Immunization and Respiratory Diseases (NCIRD)))}}</ref> although popular devices require {{val|5|-|10|u=min}} exposure and may deteriorate some materials over time.<ref>{{#invoke:cite news ||title=Yes, UV phone sanitizers work. That doesn't mean you need one. |url=https://www.washingtonpost.com/lifestyle/2021/02/16/uv-sanitizer-phone-covid-germs/ |access-date=29 April 2022 |newspaper=The Washington Post |date=16 February 2021}}</ref> A datasheet comprising the authorised substances to disinfection in the food industry (including suspension or surface tested, kind of surface, use dilution, disinfectant and inoculum volumes) can be seen in the supplementary material of.<ref name="disinfection-foodindus">{{#invoke:cite journal || vauthors = Pedreira A, Taşkın Y, García MR | title = A Critical Review of Disinfection Processes to Control SARS-CoV-2 Transmission in the Food Industry | journal = Foods | volume = 10 | issue = 2 | page = 283 | date = January 2021 | pmid = 33572531 | pmc = 7911259 | doi = 10.3390/foods10020283 | s2cid = 231900820 | doi-access = free | title-link = doi }}</ref>

=== Self-isolation ===
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Self-isolation at home has been recommended for those diagnosed with COVID‑19 and those who suspect they have been infected. Health agencies have issued detailed instructions for proper self-isolation.<ref name="pmid33012884">{{#invoke:cite journal||display-authors=6|vauthors=Patiño-Lugo DF, Vélez M, Velásquez Salazar P, Vera-Giraldo CY, Vélez V, Marín IC, Ramírez PA, Quintero SP, Castrillón Martínez E, Pineda Higuita DA, Henandez G|date=June 2020|title=Non-pharmaceutical interventions for containment, mitigation and suppression of COVID-19 infection|journal=Colombia Medica|volume=51|issue=2|pages=e4266|doi=10.25100/cm.v51i2.4266|pmc=7518730 |pmid=33012884}}</ref> Many governments have mandated or recommended self-quarantine for entire populations. The strongest self-quarantine instructions have been issued to those in high-risk groups.<ref name="lZR3i">{{#invoke:Cite web||title=COVID-19 Informational Resources for High-Risk Groups {{!}} Keeping Education ACTIVE {{!}} Partnership to Fight Chronic Disease|url=https://www.fightchronicdisease.org/resources/covid-19-informational-resources-high-risk-groups|access-date=31 May 2020|website=fightchronicdisease.org}}</ref> Those who may have been exposed to someone with COVID‑19 and those who have recently travelled to a country or region with the widespread transmission have been advised to self-quarantine for 14 days from the time of last possible exposure.<ref>{{#invoke:Cite web||url=https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html |title=Quarantine and Isolation |date=29 July 2021 |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=12 August 2021 }}</ref>

=== International travel-related control measures ===
A 2021 Cochrane rapid review found that based upon low-certainty evidence, international travel-related control measures such as restricting cross-border travel may help to contain the spread of COVID‑19.<ref name="Burns-2021">{{#invoke:cite journal || vauthors = Burns J, Movsisyan A, Stratil JM, Biallas RL, Coenen M, Emmert-Fees KM, Geffert K, Hoffmann S, Horstick O, Laxy M, Klinger C, Kratzer S, Litwin T, Norris S, Pfadenhauer LM, von Philipsborn P, Sell K, Stadelmaier J, Verboom B, Voss S, Wabnitz K, Rehfuess E | display-authors = 6 | title = International travel-related control measures to contain the COVID-19 pandemic: a rapid review | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | pages = CD013717 | date = March 2021 | issue = 3 | pmid = 33763851 | doi = 10.1002/14651858.CD013717.pub2 | pmc = 8406796 | s2cid = 232356197 | collaboration = Cochrane Public Health Group }}</ref> Additionally, symptom/exposure-based screening measures at borders may miss many positive cases.<ref name="Burns-2021" /> While test-based border screening measures may be more effective, it could also miss many positive cases if only conducted upon arrival without follow-up. The review concluded that a minimum 10-day quarantine may be beneficial in preventing the spread of COVID‑19 and may be more effective if combined with an additional control measure like border screening.<ref name="Burns-2021" />

== Treatment ==
[[File:An overview of COVID-19 therapeutics and drugs.webp|thumb|An overview of COVID-19 therapeutics and drugs]]<!-- CONTENT TRANSCLUDED. CAN BE EDITED WITHIN MANAGEMENT OF COVID-19 -->
{{Excerpt|Treatment and management of COVID-19|paragraphs=1-4|hat=no}}

==Prognosis and risk factors==
<noinclude>{{See also|COVID-19 pandemic death rates by country}}</noinclude>
<!-- THE FOLLOWING TWO PARAGRAPHS ARE TRANSCLUDED INTO THE COVID-19 PANDEMIC ARTICLE -->

The severity of COVID‑19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the [[Medicine:Common cold|common cold]]. In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalisation.<ref name="pmid33087398">{{#invoke:cite journal || vauthors = Doshi P | title = Will covid-19 vaccines save lives? Current trials aren't designed to tell us | journal = BMJ | volume = 371 | pages = m4037 | date = October 2020 | pmid = 33087398 | doi = 10.1136/bmj.m4037 | s2cid = 224817161 }}</ref> Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks.<ref name="WHOReport24Feb2020" /> The Italian [[Organization:Istituto Superiore di Sanità|Istituto Superiore di Sanità]] reported that the median time between the onset of symptoms and death was twelve days, with seven being hospitalised. However, people transferred to an ICU had a median time of ten days between hospitalisation and death.<ref name="ISSCharacteristics" /> Abnormal sodium levels during hospitalisation with COVID-19 are associated with poor prognoses: high sodium with a greater risk of death, and low sodium with an increased chance of needing ventilator support.<ref>{{#invoke:cite journal || vauthors = Tzoulis P, Waung JA, Bagkeris E, Hussein Z, Biddanda A, Cousins J, Dewsnip A, Falayi K, McCaughran W, Mullins C, Naeem A, Nwokolo M, Quah H, Bitat S, Deyab E, Ponnampalam S, Bouloux PM, Montgomery H, Baldeweg SE | display-authors = 6 | title = Dysnatremia is a Predictor for Morbidity and Mortality in Hospitalized Patients with COVID-19 | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 106 | issue = 6 | pages = 1637–1648 | date = May 2021 | pmid = 33624101 | pmc = 7928894 | doi = 10.1210/clinem/dgab107 }}</ref><ref>{{#invoke:cite journal || vauthors = Tzoulis P, Grossman AB, Baldeweg SE, Bouloux P, Kaltsas G | title = MANAGEMENT OF ENDOCRINE DISEASE: Dysnatraemia in COVID-19: prevalence, prognostic impact, pathophysiology, and management | journal = European Journal of Endocrinology | volume = 185 | issue = 4 | pages = R103–R111 | date = September 2021 | pmid = 34370712 | pmc = 8428074 | doi = 10.1530/EJE-21-0281 }}</ref> Prolonged prothrombin time and elevated [[Chemistry:C-reactive protein|C-reactive protein]] levels on admission to the hospital are associated with severe course of COVID‑19 and with a transfer to ICU.<ref>{{#invoke:cite journal || vauthors = Baranovskii DS, Klabukov ID, Krasilnikova OA, Nikogosov DA, Polekhina NV, Baranovskaia DR, Laberko LA, Maneksha S, Harry TV, Durbin RP | display-authors = 6 | title = Letter: Acid secretion by gastric mucous membrane | journal = The American Journal of Physiology | volume = 229 | issue = 6 | pages = 21–25 | date = December 1975 | pmid = 33210948<!-- Despite the error message it generates, the PMID is correct and valid as of 29 November 2020. --> | pmc = 7738209 | doi = 10.1080/03007995.2020.1853510 | s2cid = 227065216 }}</ref><ref>{{#invoke:cite journal || vauthors = Christensen B, Favaloro EJ, Lippi G, Van Cott EM | title = Hematology Laboratory Abnormalities in Patients with Coronavirus Disease 2019 (COVID-19) | journal = Seminars in Thrombosis and Hemostasis | volume = 46 | issue = 7 | pages = 845–849 | date = October 2020 | pmid = 32877961 | pmc = 7645834 | doi = 10.1055/s-0040-1715458 }}</ref>

Some early studies suggest 10% to 20% of people with COVID‑19 will experience symptoms lasting longer than a month.<ref name="NIHRreportSep20">{{#invoke:cite journal||date=15 October 2020 |title=Living with Covid19 |url=https://evidence.nihr.ac.uk/themedreview/living-with-covid19/ |periodical=NIHR Themed Reviews |publisher=National Institute for Health Research |doi=10.3310/themedreview_41169 |doi-access=free |title-link=doi}}</ref><ref name="HvIJa">{{#invoke:Cite web||date=6 June 2020|title=How long does COVID-19 last?|url=https://covid.joinzoe.com/post/covid-long-term|access-date=15 October 2020|publisher=UK COVID Symptom Study}}</ref> A majority of those who were admitted to hospital with severe disease report long-term problems including fatigue and shortness of breath.<ref name="UniWashingtonSep20">{{#invoke:Cite web||url=https://www.doh.wa.gov/Portals/1/Documents/1600/coronavirus/SummaryCOVIDLong%20termHealthEffects9-1-2020.pdf |title=Summary of COVID-19 Long Term Health Effects: Emerging evidence and Ongoing Investigation |publisher=[[Organization:University of Washington|University of Washington]] |date=1 September 2020 |access-date=15 October 2020 |archive-date=18 December 2020 |archive-url=https://web.archive.org/web/20201218080009/https://www.doh.wa.gov/Portals/1/Documents/1600/coronavirus/SummaryCOVIDLong%20termHealthEffects9-1-2020.pdf |url-status=dead}}</ref> On 30 October 2020, WHO chief Tedros Adhanom warned that "to a significant number of people, the COVID virus poses a range of serious long-term effects." He has described the vast spectrum of COVID‑19 symptoms that fluctuate over time as "really concerning". They range from fatigue, a cough and shortness of breath, to inflammation and injury of major organs{{snd}}including the lungs and heart, and also neurological and psychologic effects. Symptoms often overlap and can affect any system in the body. Infected people have reported cyclical bouts of fatigue, headaches, months of complete exhaustion, mood swings, and other symptoms. Tedros therefore concluded that a strategy of achieving [[Medicine:Herd immunity|herd immunity]] by infection, rather than vaccination, is "morally unconscionable and unfeasible".<ref name="OaTsI">{{#invoke:Cite web|| title=Long-term symptoms of COVID-19 'really concerning', says WHO chief | website=UN News | date=30 October 2020 | url=https://news.un.org/en/story/2020/10/1076562 | access-date=7 March 2021}}</ref>

In terms of hospital readmissions about 9% of 106,000 individuals had to return for hospital treatment within two months of discharge. The average to readmit was eight days since first hospital visit. There are several risk factors that have been identified as being a cause of multiple admissions to a hospital facility. Among these are advanced age (above 65 years of age) and presence of a chronic condition such as diabetes, COPD, heart failure or chronic kidney disease.<ref name="rArHO">{{#invoke:Cite web||title=Coronavirus disease 2019 (COVID-19) – Prognosis |url=https://bestpractice.bmj.com/topics/en-us/3000168/prognosis |website=BMJ |access-date=15 November 2020}}</ref><ref name="CtbMg">{{#invoke:cite journal || vauthors = Lavery AM, Preston LE, Ko JY, Chevinsky JR, DeSisto CL, Pennington AF, Kompaniyets L, Datta SD, Click ES, Golden T, Goodman AB, Mac Kenzie WR, Boehmer TK, Gundlapalli AV | display-authors = 6 | title = Characteristics of Hospitalized COVID-19 Patients Discharged and Experiencing Same-Hospital Readmission – United States, March–August 2020 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 69 | issue = 45 | pages = 1695–1699 | date = November 2020 | pmid = 33180754 | pmc = 7660660 | doi = 10.15585/mmwr.mm6945e2 }}</ref>

According to scientific reviews smokers are more likely to require intensive care or die compared to non-smokers.<ref>{{#invoke:cite journal || vauthors = Vardavas CI, Nikitara K | title = COVID-19 and smoking: A systematic review of the evidence | journal = Tobacco Induced Diseases | volume = 18 | pages = 20 | date = March 2020 | pmid = 32206052 | pmc = 7083240 | doi = 10.18332/tid/119324 }}</ref><ref name="engin-review">{{#invoke:cite journal || vauthors = Engin AB, Engin ED, Engin A | title = Two important controversial risk factors in SARS-CoV-2 infection: Obesity and smoking | journal = Environmental Toxicology and Pharmacology | volume = 78 | pages = 103411 | date = August 2020 | pmid = 32422280 | pmc = 7227557 | doi = 10.1016/j.etap.2020.103411 }}</ref> Acting on the same ACE2 pulmonary receptors affected by smoking, air pollution has been correlated with the disease.<ref name="engin-review" /> Short-term<ref>{{#invoke:cite journal || vauthors = Setti L, Passarini F, De Gennaro G, Barbieri P, Licen S, Perrone MG, Piazzalunga A, Borelli M, Palmisani J, Di Gilio A, Rizzo E, Colao A, Piscitelli P, Miani A | display-authors = 6 | title = Potential role of particulate matter in the spreading of COVID-19 in Northern Italy: first observational study based on initial epidemic diffusion | journal = BMJ Open | volume = 10 | issue = 9 | pages = e039338 | date = September 2020 | pmid = 32973066 | doi = 10.1136/bmjopen-2020-039338 | pmc = 7517216 }}</ref> and chronic<ref>{{#invoke:cite journal || vauthors = Wu X, Nethery RC, Sabath MB, Braun D, Dominici F | title = Air pollution and COVID-19 mortality in the United States: Strengths and limitations of an ecological regression analysis | journal = Science Advances | volume = 6 | issue = 45 | pages = eabd4049 | date = November 2020 | pmid = 33148655 | doi = 10.1126/sciadv.abd4049 | pmc = 7673673 | bibcode = 2020SciA....6.4049W }}</ref> exposure to air pollution seems to enhance morbidity and mortality from COVID‑19.<ref>{{#invoke:cite journal|| vauthors = Pansini R, Fornacca D |date=June 2021|title=Early Spread of COVID-19 in the Air-Polluted Regions of Eight Severely Affected Countries|journal=Atmosphere|volume=12|issue=6|pages=795|doi=10.3390/atmos12060795|bibcode=2021Atmos..12..795P|doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Comunian S, Dongo D, Milani C, Palestini P | title = Air Pollution and Covid-19: The Role of Particulate Matter in the Spread and Increase of Covid-19's Morbidity and Mortality | journal = International Journal of Environmental Research and Public Health | volume = 17 | issue = 12 | pages = 4487 | date = June 2020 | pmid = 32580440 | doi = 10.3390/ijerph17124487 | pmc = 7345938 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Domingo JL, Marquès M, Rovira J | title = Influence of airborne transmission of SARS-CoV-2 on COVID-19 pandemic. A review | journal = Environmental Research | volume = 188 | pages = 109861 | date = September 2020 | pmid = 32718835 | pmc = 7309850 | doi = 10.1016/j.envres.2020.109861 | bibcode = 2020ER....188j9861D }}</ref> Pre-existing heart and lung diseases<ref>{{#invoke:Cite web||url=https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-who-is-at-risk/art-20483301|title=COVID-19: Who's at higher risk of serious symptoms?|website=Mayo Clinic}}</ref> and also obesity, especially in conjunction with [[Medicine:Fatty liver disease|fatty liver disease]], contributes to an increased health risk of COVID‑19.<ref name="engin-review" /><ref>{{#invoke:cite journal || vauthors = Tamara A, Tahapary DL | title = Obesity as a predictor for a poor prognosis of COVID-19: A systematic review | journal = Diabetes & Metabolic Syndrome | volume = 14 | issue = 4 | pages = 655–659 | date = July 2020 | pmid = 32438328 | pmc = 7217103 | doi = 10.1016/j.dsx.2020.05.020 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Petrakis D, Margină D, Tsarouhas K, Tekos F, Stan M, Nikitovic D, Kouretas D, Spandidos DA, Tsatsakis A | display-authors = 6 | title = Obesity – A risk factor for increased COVID-19, severity and lethality (Review) | journal = Molecular Medicine Reports | volume = 22 | issue = 1 | pages = 9–19 | date = July 2020 | pmid = 32377709 | pmc = 7248467 | doi = 10.3892/mmr.2020.11127 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal ||vauthors=Roca-Fernández A, Dennis A, Nicholls R, McGonigle J, Kelly M, Banerjee R, Banerjee A, Sanyal AJ |display-authors=6 |date=29 March 2021 |title=Hepatic Steatosis, Rather Than Underlying Obesity, Increases the Risk of Infection and Hospitalization for COVID-19 |journal=Frontiers in Medicine |volume=8 |page=636637 |doi=10.3389/fmed.2021.636637 |pmid=33855033 |pmc=8039134 |issn=2296-858X|doi-access = free | title-link = doi }}</ref>

It is also assumed that those that are immunocompromised are at higher risk of getting severely sick from SARS-CoV-2.<ref>{{#invoke:Cite web||url=https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/immunocompromised.html|title=Coronavirus Disease 2019 (COVID-19)|date=11 February 2020|website=U.S. Centers for Disease Control and Prevention (CDC) }}</ref> One research study that looked into the COVID‑19 infections in hospitalised kidney transplant recipients found a mortality rate of 11%.<ref>{{#invoke:cite journal || vauthors = Devresse A, Belkhir L, Vo B, Ghaye B, Scohy A, Kabamba B, Goffin E, De Greef J, Mourad M, De Meyer M, Yombi JC, Kanaan N | display-authors = 6 | title = COVID-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 22 Cases From Belgium | journal = Kidney Medicine | volume = 2 | issue = 4 | pages = 459–466 | date = November 2020 | pmid = 32775986 | pmc = 7295531 | doi = 10.1016/j.xkme.2020.06.001 }}</ref>

Men with untreated hypogonadism were 2.4 times more likely than men with eugonadism to be hospitalised if they contracted COVID-19; Hypogonad men treated with [[Chemistry:Testosterone|testosterone]] were less likely to be hospitalised for COVID-19 than men who were not treated for hypogonadism.<ref name="jama">{{#invoke:cite journal || vauthors = Dhindsa S, Champion C, Deol E, Lui M, Campbell R, Newman J, Yeggalam A, Nadella S, Ahir V, Shrestha E, Kannampallil T, Diwan A | display-authors = 6 | title = Association of Male Hypogonadism With Risk of Hospitalization for COVID-19 | journal = JAMA Network Open | volume = 5 | issue = 9 | pages = e2229747 | date = September 2022 | pmid = 36053534 | doi = 10.1001/jamanetworkopen.2022.29747 | pmc = 9440397 }}</ref>

=== Genetic risk factors ===
[[Biology:Genetics|Genetics]] plays an important role in the ability to fight off Covid.<ref name="pmid33888907">{{#invoke:cite journal || vauthors = Shelton JF, Shastri AJ, Ye C, Weldon CH, Filshtein-Sonmez T, Coker D, Symons A, Esparza-Gordillo J, Aslibekyan S, Auton A | display-authors = 6 | title = Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity | journal = Nature Genetics | volume = 53 | issue = 6 | pages = 801–808 | date = June 2021 | pmid = 33888907 | doi = 10.1038/s41588-021-00854-7 | s2cid = 233372385 }}</ref> For instance, those that do not produce detectable type I interferons or produce [[Biology:Autoantibody|auto-antibodies]] against these may get much sicker from COVID‑19.<ref>{{#invoke:Cite web||title=One in Seven Dire COVID Cases May Result from a Faulty Immune Response|url=https://www.scientificamerican.com/article/one-in-seven-dire-covid-cases-may-result-from-a-faulty-immune-response/|website=Scientific American|vauthors=Wallis C}}</ref><ref>{{#invoke:cite journal || vauthors = Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Béziat V, Manry J, Shaw E, Haljasmägi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodríguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J, Tsang JS, Goldbach-Mansky R, Kisand K, Lionakis MS, Puel A, Zhang SY, Holland SM, Gorochov G, Jouanguy E, Rice CM, Cobat A, Notarangelo LD, Abel L, Su HC, Casanova JL | display-authors = 6 | title = Autoantibodies against type I IFNs in patients with life-threatening COVID-19 | journal = Science | volume = 370 | issue = 6515 | pages = eabd4585 | date = October 2020 | pmid = 32972996 | pmc = 7857397 | doi = 10.1126/science.abd4585 | s2cid = 221914095 | title-link = doi | doi-access = free }}</ref> Genetic screening is able to detect interferon effector genes.<ref>{{#invoke:cite journal || vauthors = Fusco DN, Brisac C, John SP, Huang YW, Chin CR, Xie T, Zhao H, Jilg N, Zhang L, Chevaliez S, Wambua D, Lin W, Peng L, Chung RT, Brass AL | display-authors = 6 | title = A genetic screen identifies interferon-α effector genes required to suppress hepatitis C virus replication | journal = Gastroenterology | volume = 144 | issue = 7 | pages = 1438–49, 1449.e1-9 | date = June 2013 | pmid = 23462180 | pmc = 3665646 | doi = 10.1053/j.gastro.2013.02.026 }}</ref> Some genetic variants are risk factors in specific populations. For instance, an [[Biology:Allele|allele]] of the DOCK2 gene (dedicator of cytokinesis 2 gene) is a common risk factor in Asian populations but much less common in Europe. The mutation leads to lower expression of DOCK2 especially in younger patients with severe Covid.<ref>{{#invoke:cite journal || vauthors = Namkoong H, Edahiro R, Takano T, Nishihara H, Shirai Y, Sonehara K, Tanaka H, Azekawa S, Mikami Y, Lee H, Hasegawa T, Okudela K, Okuzaki D, Motooka D, Kanai M, Naito T, Yamamoto K, Wang QS, Saiki R, Ishihara R, Matsubara Y, Hamamoto J, Hayashi H, Yoshimura Y, Tachikawa N, Yanagita E, Hyugaji T, Shimizu E, Katayama K, Kato Y, Morita T, Takahashi K, Harada N, Naito T, Hiki M, Matsushita Y, Takagi H, Aoki R, Nakamura A, Harada S, Sasano H, Kabata H, Masaki K, Kamata H, Ikemura S, Chubachi S, Okamori S, Terai H, Morita A, Asakura T, Sasaki J, Morisaki H, Uwamino Y, Nanki K, Uchida S, Uno S, Nishimura T, Ishiguro T, Isono T, Shibata S, Matsui Y, Hosoda C, Takano K, Nishida T, Kobayashi Y, Takaku Y, Takayanagi N, Ueda S, Tada A, Miyawaki M, Yamamoto M, Yoshida E, Hayashi R, Nagasaka T, Arai S, Kaneko Y, Sasaki K, Tagaya E, Kawana M, Arimura K, Takahashi K, Anzai T, Ito S, Endo A, Uchimura Y, Miyazaki Y, Honda T, Tateishi T, Tohda S, Ichimura N, Sonobe K, Sassa CT, Nakajima J, Nakano Y, Nakajima Y, Anan R, Arai R, Kurihara Y, Harada Y, Nishio K, Ueda T, Azuma M, Saito R, Sado T, Miyazaki Y, Sato R, Haruta Y, Nagasaki T, Yasui Y, Hasegawa Y, Mutoh Y, Kimura T, Sato T, Takei R, Hagimoto S, Noguchi Y, Yamano Y, Sasano H, Ota S, Nakamori Y, Yoshiya K, Saito F, Yoshihara T, Wada D, Iwamura H, Kanayama S, Maruyama S, Yoshiyama T, Ohta K, Kokuto H, Ogata H, Tanaka Y, Arakawa K, Shimoda M, Osawa T, Tateno H, Hase I, Yoshida S, Suzuki S, Kawada M, Horinouchi H, Saito F, Mitamura K, Hagihara M, Ochi J, Uchida T, Baba R, Arai D, Ogura T, Takahashi H, Hagiwara S, Nagao G, Konishi S, Nakachi I, Murakami K, Yamada M, Sugiura H, Sano H, Matsumoto S, Kimura N, Ono Y, Baba H, Suzuki Y, Nakayama S, Masuzawa K, Namba S, Suzuki K, Naito Y, Liu YC, Takuwa A, Sugihara F, Wing JB, Sakakibara S, Hizawa N, Shiroyama T, Miyawaki S, Kawamura Y, Nakayama A, Matsuo H, Maeda Y, Nii T, Noda Y, Niitsu T, Adachi Y, Enomoto T, Amiya S, Hara R, Yamaguchi Y, Murakami T, Kuge T, Matsumoto K, Yamamoto Y, Yamamoto M, Yoneda M, Kishikawa T, Yamada S, Kawabata S, Kijima N, Takagaki M, Sasa N, Ueno Y, Suzuki M, Takemoto N, Eguchi H, Fukusumi T, Imai T, Fukushima M, Kishima H, Inohara H, Tomono K, Kato K, Takahashi M, Matsuda F, Hirata H, Takeda Y, Koh H, Manabe T, Funatsu Y, Ito F, Fukui T, Shinozuka K, Kohashi S, Miyazaki M, Shoko T, Kojima M, Adachi T, Ishikawa M, Takahashi K, Inoue T, Hirano T, Kobayashi K, Takaoka H, Watanabe K, Miyazawa N, Kimura Y, Sado R, Sugimoto H, Kamiya A, Kuwahara N, Fujiwara A, Matsunaga T, Sato Y, Okada T, Hirai Y, Kawashima H, Narita A, Niwa K, Sekikawa Y, Nishi K, Nishitsuji M, Tani M, Suzuki J, Nakatsumi H, Ogura T, Kitamura H, Hagiwara E, Murohashi K, Okabayashi H, Mochimaru T, Nukaga S, Satomi R, Oyamada Y, Mori N, Baba T, Fukui Y, Odate M, Mashimo S, Makino Y, Yagi K, Hashiguchi M, Kagyo J, Shiomi T, Fuke S, Saito H, Tsuchida T, Fujitani S, Takita M, Morikawa D, Yoshida T, Izumo T, Inomata M, Kuse N, Awano N, Tone M, Ito A, Nakamura Y, Hoshino K, Maruyama J, Ishikura H, Takata T, Odani T, Amishima M, Hattori T, Shichinohe Y, Kagaya T, Kita T, Ohta K, Sakagami S, Koshida K, Hayashi K, Shimizu T, Kozu Y, Hiranuma H, Gon Y, Izumi N, Nagata K, Ueda K, Taki R, Hanada S, Kawamura K, Ichikado K, Nishiyama K, Muranaka H, Nakamura K, Hashimoto N, Wakahara K, Sakamoto K, Omote N, Ando A, Kodama N, Kaneyama Y, Maeda S, Kuraki T, Matsumoto T, Yokote K, Nakada TA, Abe R, Oshima T, Shimada T, Harada M, Takahashi T, Ono H, Sakurai T, Shibusawa T, Kimizuka Y, Kawana A, Sano T, Watanabe C, Suematsu R, Sageshima H, Yoshifuji A, Ito K, Takahashi S, Ishioka K, Nakamura M, Masuda M, Wakabayashi A, Watanabe H, Ueda S, Nishikawa M, Chihara Y, Takeuchi M, Onoi K, Shinozuka J, Sueyoshi A, Nagasaki Y, Okamoto M, Ishihara S, Shimo M, Tokunaga Y, Kusaka Y, Ohba T, Isogai S, Ogawa A, Inoue T, Fukuyama S, Eriguchi Y, Yonekawa A, Kan-O K, Matsumoto K, Kanaoka K, Ihara S, Komuta K, Inoue Y, Chiba S, Yamagata K, Hiramatsu Y, Kai H, Asano K, Oguma T, Ito Y, Hashimoto S, Yamasaki M, Kasamatsu Y, Komase Y, Hida N, Tsuburai T, Oyama B, Takada M, Kanda H, Kitagawa Y, Fukuta T, Miyake T, Yoshida S, Ogura S, Abe S, Kono Y, Togashi Y, Takoi H, Kikuchi R, Ogawa S, Ogata T, Ishihara S, Kanehiro A, Ozaki S, Fuchimoto Y, Wada S, Fujimoto N, Nishiyama K, Terashima M, Beppu S, Yoshida K, Narumoto O, Nagai H, Ooshima N, Motegi M, Umeda A, Miyagawa K, Shimada H, Endo M, Ohira Y, Watanabe M, Inoue S, Igarashi A, Sato M, Sagara H, Tanaka A, Ohta S, Kimura T, Shibata Y, Tanino Y, Nikaido T, Minemura H, Sato Y, Yamada Y, Hashino T, Shinoki M, Iwagoe H, Takahashi H, Fujii K, Kishi H, Kanai M, Imamura T, Yamashita T, Yatomi M, Maeno T, Hayashi S, Takahashi M, Kuramochi M, Kamimaki I, Tominaga Y, Ishii T, Utsugi M, Ono A, Tanaka T, Kashiwada T, Fujita K, Saito Y, Seike M, Watanabe H, Matsuse H, Kodaka N, Nakano C, Oshio T, Hirouchi T, Makino S, Egi M, Omae Y, Nannya Y, Ueno T, Katayama K, Ai M, Fukui Y, Kumanogoh A, Sato T, Hasegawa N, Tokunaga K, Ishii M, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K, Okada Y | display-authors = 6 | title = DOCK2 is involved in the host genetics and biology of severe COVID-19 | journal = Nature | volume = 609 | issue = 7928 | pages = 754–760 | date = September 2022 | pmid = 35940203 | pmc = 9492544 | doi = 10.1038/s41586-022-05163-5 | bibcode = 2022Natur.609..754N }}</ref> In fact, many other genes and genetic variants have been found that determine the outcome of SARS-CoV-2 infections.<ref>{{#invoke:cite journal || vauthors = Kousathanas A, Pairo-Castineira E, Rawlik K, Stuckey A, Odhams CA, Walker S, Russell CD, Malinauskas T, Wu Y, Millar J, Shen X, Elliott KS, Griffiths F, Oosthuyzen W, Morrice K, Keating S, Wang B, Rhodes D, Klaric L, Zechner M, Parkinson N, Siddiq A, Goddard P, Donovan S, Maslove D, Nichol A, Semple MG, Zainy T, Maleady-Crowe F, Todd L, Salehi S, Knight J, Elgar G, Chan G, Arumugam P, Patch C, Rendon A, Bentley D, Kingsley C, Kosmicki JA, Horowitz JE, Baras A, Abecasis GR, Ferreira MA, Justice A, Mirshahi T, Oetjens M, Rader DJ, Ritchie MD, Verma A, Fowler TA, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJ, Elliott P, Walsh T, Tenesa A, Fawkes A, Murphy L, Rowan K, Ponting CP, Vitart V, Wilson JF, Yang J, Bretherick AD, Scott RH, Hendry SC, Moutsianas L, Law A, Caulfield MJ, Baillie JK | display-authors = 6 | title = Whole-genome sequencing reveals host factors underlying critical COVID-19 | journal = Nature | volume = 607 | issue = 7917 | pages = 97–103 | date = July 2022 | pmid = 35255492 | pmc = 9259496 | doi = 10.1038/s41586-022-04576-6 }}</ref>

=== Children ===

While very young children have experienced lower rates of infection, older children have a rate of infection that is similar to the population as a whole.<ref>{{#invoke:Cite web||title=COVID-19 in children and the role of school settings in transmission – first update |url=https://www.ecdc.europa.eu/en/publications-data/children-and-school-settings-covid-19-transmission |website=European Centre for Disease Prevention and Control |access-date=6 April 2021 |date=23 December 2020}}</ref><ref>{{#invoke:Cite web||title=Estimated Disease Burden of COVID-19 |url=https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burden.html |website=U.S. Centers for Disease Control and Prevention (CDC) |access-date=6 April 2021 |date=11 February 2020}}</ref> Children are likely to have milder symptoms and are at lower risk of severe disease than adults.<ref name="Reardon">{{#invoke:cite journal || vauthors = Reardon S |title=Why don't kids tend to get as sick from Covid-19? |journal=Knowable Magazine |date=2 September 2021 |doi=10.1146/knowable-090121-1 |s2cid=239653475 |url=https://knowablemagazine.org/article/health-disease/2021/why-dont-kids-tend-get-sick-covid19 |access-date=7 September 2021}}</ref> The CDC reports that in the US roughly a third of hospitalised children were admitted to the ICU,<ref>{{#invoke:Cite web||title=Information for Pediatric Healthcare Providers |url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html |website=U.S. Centers for Disease Control and Prevention (CDC) |access-date=6 April 2021 |date=11 February 2020}}</ref> while a European multinational study of hospitalised children from June 2020, found that about 8% of children admitted to a hospital needed intensive care.<ref>{{#invoke:cite journal || vauthors = Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Calò Carducci FI, Gabrovska N, Velizarova S, Prunk P, Osterman V, Krivec U, Lo Vecchio A, Shingadia D, Soriano-Arandes A, Melendo S, Lanari M, Pierantoni L, Wagner N, L'Huillier AG, Heininger U, Ritz N, Bandi S, Krajcar N, Roglić S, Santos M, Christiaens C, Creuven M, Buonsenso D, Welch SB, Bogyi M, Brinkmann F, Tebruegge M | display-authors = 6 | title = COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study | journal = The Lancet. Child & Adolescent Health | volume = 4 | issue = 9 | pages = 653–661 | date = September 2020 | pmid = 32593339 | pmc = 7316447 | doi = 10.1016/S2352-4642(20)30177-2 }}</ref> Four of the 582 children (0.7%) in the European study died, but the actual mortality rate may be "substantially lower" since milder cases that did not seek medical help were not included in the study.<ref>{{#invoke:cite journal || vauthors = Fang L, Karakiulakis G, Roth M | title = Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? | journal = The Lancet. Respiratory Medicine | volume = 8 | issue = 4 | pages = e21 | date = April 2020 | pmid = 32171062 | pmc = 7118626 | doi = 10.1016/S0140-6736(20)30311-1 }}</ref><ref name="CDC 2020children">{{#invoke:Cite web||url=https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/children-faq.html|title=Coronavirus Disease 2019 (COVID-19)|date=11 February 2020|website=U.S. Centers for Disease Control and Prevention (CDC) |access-date=2 March 2020|archive-url=https://web.archive.org/web/20200302064104/https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/children-faq.html|archive-date=2 March 2020|url-status=live}}</ref>

=== Long-term effects ===

Around 10% to 30% of non-hospitalised people with COVID-19 go on to develop long COVID. For those that do need hospitalisation, the incidence of long-term effects is over 50%.<ref name="davis">{{#invoke:cite journal ||vauthors=Davis HE, McCorkell L, Vogel JM, Topol EJ |date=March 2023 |title=Long COVID: major findings, mechanisms and recommendations |journal=Nature Reviews. Microbiology |volume=21 |issue=3 |pages=133–146 |doi=10.1038/s41579-022-00846-2 |pmc=9839201 |pmid=36639608}}</ref> Long COVID is an often severe multisystem disease with a large set of symptoms. There are likely various, possibly coinciding, causes.<ref name="davis" /> Organ damage from the acute infection can explain a part of the symptoms, but long COVID is also observed in people where organ damage seems to be absent.<ref name="pmid35594336">{{#invoke:cite journal ||vauthors=Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, Primus-de Jong C, Cleemput I, Van den Heede K |date=December 2022 |title=Pathophysiology and mechanism of long COVID: a comprehensive review |url= |journal=Annals of Medicine |volume=54 |issue=1 |pages=1473–1487 |doi=10.1080/07853890.2022.2076901 |pmc=9132392 |pmid=35594336}}</ref>

By a variety of mechanisms, the lungs are the organs most affected in COVID{{nbhyph}}19.<ref name="Torres">{{#invoke:cite journal || vauthors = Torres-Castro R, Vasconcello-Castillo L, Alsina-Restoy X, Solis-Navarro L, Burgos F, Puppo H, Vilaró J | display-authors = 6 | title = Respiratory function in patients post-infection by COVID-19: a systematic review and meta-analysis | journal = Pulmonology | date = November 2020 | volume = 27 | issue = 4 | pages = 328–337 | pmid = 33262076 | pmc = 7687368 | doi = 10.1016/j.pulmoe.2020.10.013 | publisher = Elsevier BV | s2cid = 227162748 }}</ref> In people requiring hospital admission, up to 98% of CT scans performed show lung abnormalities after 28 days of illness even if they had clinically improved.<ref>{{#invoke:cite journal || vauthors = Shaw B, Daskareh M, Gholamrezanezhad A | title = The lingering manifestations of COVID-19 during and after convalescence: update on long-term pulmonary consequences of coronavirus disease 2019 (COVID-19) | journal = La Radiologia Medica | volume = 126 | issue = 1 | pages = 40–46 | date = January 2021 | pmid = 33006087 | pmc = 7529085 | doi = 10.1007/s11547-020-01295-8 }}</ref> People with advanced age, severe disease, prolonged ICU stays, or who smoke are more likely to have long-lasting effects, including pulmonary fibrosis.<ref name="Rai">{{#invoke:cite journal || vauthors = Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, Jia JL, Li LM, Mao HL, Zhou XM, Luo H, Gao YF, Xu AG | display-authors = 6 | title = Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery | journal = eClinicalMedicine | volume = 25 | pages = 100463 | date = August 2020 | pmc = 7654356 | doi = 10.1016/j.ijtb.2020.11.003 | pmid = 32838236 }}</ref> Overall, approximately one-third of those investigated after four weeks will have findings of [[Medicine:Pulmonary fibrosis|pulmonary fibrosis]] or reduced lung function as measured by [[Medicine:DLCO|DLCO]], even in asymptomatic people, but with the suggestion of continuing improvement with the passing of more time.<ref name="Torres" /> After severe disease, lung function can take anywhere from three months to a year or more to return to previous levels.<ref>{{#invoke:Cite news||title=COVID-19 Lung Damage |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/what-coronavirus-does-to-the-lungs |publisher=Johns Hopkins Medicine |access-date=21 May 2022 |date=28 February 2022}}</ref>

The risks of [[Medicine:Cognitive deficit|cognitive deficit]], [[Medicine:Dementia|dementia]], psychotic disorders, and [[Medicine:Epilepsy|epilepsy]] or seizures persists at an increased level two years after infection.<ref>{{#invoke:cite journal ||vauthors=Taquet M, Sillett R, Zhu L, Mendel J, Camplisson I, Dercon Q, Harrison PJ | display-authors = 6 |date=August 2022 |title=Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients |journal=The Lancet Psychiatry |doi=10.1016/S2215-0366(22)00260-7 |pmid=35987197 |pmc=9385200 |s2cid=251626731 |issn=2215-0366 |volume=9 |issue=10 |pages=815–827}}</ref>

=== Immunity ===
[[File:Diagnostics-10-00453-g001.webp|thumb|Human antibody response to SARS-CoV-2 infection]]

The [[Biology:Immune response|immune response]] by humans to SARS-CoV-2 virus occurs as a combination of the [[Biology:Cell-mediated immunity|cell-mediated immunity]] and antibody production,<ref>{{#invoke:Cite web||url=https://www.ecdc.europa.eu/en/covid-19/latest-evidence/immune-responses |title=Immune responses and correlates of protective immunity against SARS-CoV-2 |date=18 May 2021 |publisher=European Centre for Disease Prevention and Control |access-date=3 June 2021}}</ref> just as with most other infections.<ref>{{#invoke:cite journal || vauthors = Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, Levantovsky R, Malle L, Moreira A, Park MD, Pia L, Risson E, Saffern M, Salomé B, Esai Selvan M, Spindler MP, Tan J, van der Heide V, Gregory JK, Alexandropoulos K, Bhardwaj N, Brown BD, Greenbaum B, Gümüş ZH, Homann D, Horowitz A, Kamphorst AO, Curotto de Lafaille MA, Mehandru S, Merad M, Samstein RM | display-authors = 6 | title = Immunology of COVID-19: Current State of the Science | journal = Immunity | volume = 52 | issue = 6 | pages = 910–941 | date = June 2020 | pmid = 32505227 | pmc = 7200337 | doi = 10.1016/j.immuni.2020.05.002 | doi-access = free | title-link = doi }}</ref> B cells interact with T cells and begin dividing before selection into the plasma cell, partly on the basis of their affinity for antigen.<ref>{{#invoke:cite journal || vauthors = Wang Z, Muecksch F, Schaefer-Babajew D, Finkin S, Viant C, Gaebler C, Hoffmann HH, Barnes CO, Cipolla M, Ramos V, Oliveira TY, Cho A, Schmidt F, Da Silva J, Bednarski E, Aguado L, Yee J, Daga M, Turroja M, Millard KG, Jankovic M, Gazumyan A, Zhao Z, Rice CM, Bieniasz PD, Caskey M, Hatziioannou T, Nussenzweig MC | display-authors = 6 | title = Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection | journal = Nature | volume = 595 | issue = 7867 | pages = 426–431 | date = July 2021 | pmid = 34126625 | pmc = 8277577 | doi = 10.1038/s41586-021-03696-9 | bibcode = 2021Natur.595..426W }}</ref> Since SARS-CoV-2 has been in the human population only since December 2019, it remains unknown if the [[Medicine:Immunity (medical)|immunity]] is long-lasting in people who recover from the disease.<ref name="CohenJI2020Dec">{{#invoke:cite journal || vauthors = Cohen JI, Burbelo PD | title = Reinfection with SARS-CoV-2: Implications for Vaccines | journal = Clinical Infectious Diseases | date = December 2020 | pmid = 33338197 | pmc = 7799323 | doi = 10.1093/cid/ciaa1866 | s2cid = 229323810 | title-link = doi | volume = 73 | issue = 11 | pages = e4223–e4228 | doi-access = free }}</ref> The presence of neutralising antibodies in blood strongly correlates with protection from infection, but the level of neutralising antibody declines with time. Those with asymptomatic or mild disease had undetectable levels of neutralising antibody two months after infection. In another study, the level of neutralising antibodies fell four-fold one to four months after the onset of symptoms. However, the lack of antibodies in the blood does not mean antibodies will not be rapidly produced upon reexposure to SARS-CoV-2. Memory B cells specific for the spike and nucleocapsid proteins of SARS-CoV-2 last for at least six months after the appearance of symptoms.<ref name="CohenJI2020Dec" />

As of August 2021, reinfection with COVID‑19 was possible but uncommon. The first case of reinfection was documented in August 2020.<ref name="Wang-2021">{{#invoke:cite journal || vauthors = Wang J, Kaperak C, Sato T, Sakuraba A | title = COVID-19 reinfection: a rapid systematic review of case reports and case series | journal = Journal of Investigative Medicine | volume = 69 | issue = 6 | pages = 1253–1255 | date = August 2021 | pmid = 34006572 | doi = 10.1136/jim-2021-001853 |issn=1081-5589 | s2cid = 234773697 }}</ref> A systematic review found 17 cases of confirmed reinfection in medical literature as of May 2021.<ref name="Wang-2021" /> With the Omicron variant, as of 2022, reinfections have become common, albeit it is unclear how common.<ref name="abc-reinfections"/> [[Biology:SARS-CoV-2#Reinfection|COVID-19 reinfections]] are thought to likely be less severe than primary infections, especially if one was previously infected by the same variant.<ref name="abc-reinfections">{{#invoke:cite news ||title=How soon after catching COVID-19 can you get it again? |url=https://www.abc.net.au/news/health/2022-05-03/covid-19-reinfection-what-are-the-odds-of-catching-it-twice/101024180 |access-date=24 June 2022 |work=ABC News |date=2 May 2022 }}</ref>{{additional citation needed|date=July 2022}}

== Mortality ==

Several measures are commonly used to quantify mortality.<ref>{{#invoke:cite book||vauthors=((Centers for Disease Control and Prevention)) |chapter-url=https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section3.html |title=Principles of Epidemiology in Public Health Practice |edition=Third |chapter=Lesson 3: Measures of Risk Section 3: Mortality Frequency Measures |date=May 2012|publisher=U.S. Centers for Disease Control and Prevention (CDC)|access-date=28 March 2020|archive-date=28 February 2020|archive-url= https://web.archive.org/web/20200228150607/https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section3.html |url-status=live |id=No. SS1978}}</ref> These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health.<ref>{{#invoke:cite journal ||url=https://ourworldindata.org/covid-mortality-risk |title=What do we know about the risk of dying from COVID-19? |vauthors=Ritchie H, Roser M |date=25 March 2020 |veditors=Chivers T |journal=[[Organization:Our World in Data|Our World in Data]] |url-status=live |access-date=28 March 2020 |archive-date=28 March 2020 |archive-url=https://web.archive.org/web/20200328192730/https://ourworldindata.org/covid-mortality-risk}}</ref>

The [[Mortality rate|mortality rate]] reflects the number of deaths within a specific demographic group divided by the population of that demographic group. Consequently, the mortality rate reflects the prevalence as well as the severity of the disease within a given population. Mortality rates are highly correlated to age, with relatively low rates for young people and relatively high rates among the elderly.<ref name="JAMAPedsCOVID19">{{#invoke:cite journal || vauthors = Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, Rovida F, Baldanti F, Marseglia GL | display-authors = 6 | title = Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review | journal = JAMA Pediatrics | volume = 174 | issue = 9 | pages = 882–889 | date = September 2020 | pmid = 32320004 | doi = 10.1001/jamapediatrics.2020.1467 | doi-access = free | title-link = doi }}</ref><ref name="Lu Zhang Du Zhang p.">{{#invoke:cite journal || vauthors = Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong GW | display-authors = 6 | title = SARS-CoV-2 Infection in Children | journal = The New England Journal of Medicine | volume = 382 | issue = 17 | pages = 1663–1665 | date = April 2020 | pmid = 32187458 | pmc = 7121177 | doi = 10.1056/nejmc2005073 | publisher = Massachusetts Medical Society }}</ref><ref name="pediatrics_tong">{{#invoke:cite journal || vauthors = Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, Tong S | display-authors = 6 | title = Epidemiology of COVID-19 Among Children in China | journal = Pediatrics | volume = 145 | issue = 6 | pages = e20200702 | date = June 2020 | pmid = 32179660 | doi = 10.1542/peds.2020-0702 | s2cid = 219118986 | doi-access = free | title-link = doi }}</ref> In fact, one relevant factor of mortality rates is the age structure of the countries' populations. For example, the case fatality rate for COVID‑19 is lower in India than in the US since India's younger population represents a larger percentage than in the US.<ref name="Dehingia-2021">{{#invoke:cite journal||title=Sex differences in COVID-19 case fatality: do we know enough?|journal=The Lancet. Global Health|vauthors=Dehingia N|year=2021|volume=9|issue=1|pages=e14–e15|doi=10.1016/S2214-109X(20)30464-2|pmid=33160453|pmc=7834645}}</ref>

=== Case fatality rate ===
The [[Medicine:Case fatality rate|case fatality rate]] (CFR) reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is {{Cases in the COVID-19 pandemic|ratio|editlink=|ref=no}} ({{Cases in the COVID-19 pandemic|deaths|editlink=|ref=no}}/{{Cases in the COVID-19 pandemic|confirmed|editlink=|ref=no}}) as of {{Cases in the COVID-19 pandemic|date|editlink=|ref=no}}.{{Cases in the COVID-19 pandemic|ref=yes}} The number varies by region.<ref>{{#invoke:cite journal || vauthors = Lazzerini M, Putoto G | title = COVID-19 in Italy: momentous decisions and many uncertainties | journal = The Lancet. Global Health | volume = 8 | issue = 5 | pages = e641–e642 | date = May 2020 | pmid = 32199072 | pmc = 7104294 | doi = 10.1016/S2214-109X(20)30110-8 }}</ref><ref>{{#invoke:cite journal ||url=https://ourworldindata.org/covid-mortality-risk |title=What do we know about the risk of dying from COVID-19? |journal=Our World in Data |date=5 March 2020 |access-date=28 March 2020 |archive-url=https://web.archive.org/web/20200328192730/https://ourworldindata.org/covid-mortality-risk |archive-date=28 March 2020 |url-status=live| vauthors = Ritchie H, Ortiz-Ospina E, Beltekian D, Mathieu E, Hasell J, MacDonald B, Giattino C, Appel C, Rodés-Guirao L, Roser M | display-authors = 6 }}</ref>

<gallery mode="packed" heights=140 >
Cumulative confirmed COVID-19 cases.svg|Total confirmed cases over time

World map of total confirmed COVID-19 cases per million people.svg|Total confirmed cases of COVID‑19 per million people<ref>{{#invoke:Cite web||title=Total confirmed cases of COVID-19 per million people |url=https://ourworldindata.org/grapher/total-confirmed-cases-of-covid-19-per-million-people |website=Our World in Data |access-date=21 June 2022 |archive-url=https://web.archive.org/web/20200319163452/https://ourworldindata.org/grapher/total-confirmed-cases-of-covid-19-per-million-people |archive-date=19 March 2020 |url-status=live}}{{update inline|reason=referenced page and the image updated without coordination, archived version obsolete|month=August 2020|date=August 2020}}</ref>

Daily and total confirmed COVID-19 deaths, World.svg|Total confirmed deaths over time

World map of total confirmed COVID-19 deaths per million people by country.svg|Total confirmed deaths due to COVID‑19 per million people<ref>{{#invoke:Cite web||title=Cumulative confirmed COVID-19 deaths per million people |url=https://ourworldindata.org/grapher/total-covid-deaths-per-million |website=[[Organization:Our World in Data|Our World in Data]] }}</ref>

</gallery>

=== Infection fatality rate ===
A key metric in gauging the severity of COVID‑19 is the infection fatality rate (IFR), also referred to as the ''infection fatality ratio'' or ''infection fatality risk''.<ref>{{#invoke:cite journal || vauthors = Mallapaty S | title = How deadly is the coronavirus? Scientists are close to an answer | journal = Nature | volume = 582 | issue = 7813 | pages = 467–468 | date = June 2020 | pmid = 32546810 | doi = 10.1038/d41586-020-01738-2 | s2cid = 219726496 | doi-access = free | title-link = doi | bibcode = 2020Natur.582..467M }}</ref><ref>{{#invoke:cite journal || vauthors = Alwan NA, Burgess RA, Ashworth S, Beale R, Bhadelia N, Bogaert D, Dowd J, Eckerle I, Goldman LR, Greenhalgh T, Gurdasani D, Hamdy A, Hanage WP, Hodcroft EB, Hyde Z, Kellam P, Kelly-Irving M, Krammer F, Lipsitch M, McNally A, McKee M, Nouri A, Pimenta D, Priesemann V, Rutter H, Silver J, Sridhar D, Swanton C, Walensky RP, Yamey G, Ziauddeen H | display-authors = 6 | title = Scientific consensus on the COVID-19 pandemic: we need to act now | journal = Lancet | volume = 396 | issue = 10260 | pages = e71–e72 | date = October 2020 | pmid = 33069277 | pmc = 7557300 | doi = 10.1016/S0140-6736(20)32153-X }}</ref><ref>{{#invoke:cite journal || vauthors = Meyerowitz-Katz G, Merone L | title = A systematic review and meta-analysis of published research data on COVID-19 infection fatality rates | journal = International Journal of Infectious Diseases | volume = 101 | pages = 138–148 | date = December 2020 | pmid = 33007452 | pmc = 7524446 | doi = 10.1016/j.ijid.2020.09.1464 }}</ref> This metric is calculated by dividing the total number of deaths from the disease by the total number of infected individuals; hence, in contrast to the [[Medicine:Case fatality rate|CFR]], the IFR incorporates asymptomatic and undiagnosed infections as well as reported cases.<ref name="urlGeneralized trapezoidal ogive curves for fatality rate modeling">{{#invoke:cite journal || vauthors = Zhang D, Hu M, Ji Q | title = Financial markets under the global pandemic of COVID-19 | journal = Finance Research Letters | volume = 36 | pages = 101528 | date = October 2020 | pmc = 7402242 | doi = 10.1016/j.csfx.2020.100043 | pmid = 32837360 | bibcode = 2020CSFX....500043D }}</ref>

==== Estimates ====
[[File:Graph of Covid-19 Infection Fatality Ratio by age.png|thumb|The red line shows the estimate of infection fatality rate (IFR), in percentage terms, as a function of age. The shaded region depicts the 95% confidence interval for that estimate. Markers denotes specific observations used in the meta-analysis.<ref name="EJE_levinetal" />]]
[[File:Log Graph of Covid-19 Infection Fatality Ratio by age.png|thumb|The same relationship plotted on a log scale]]

A December 2020 systematic review and meta-analysis estimated that population IFR during the first wave of the pandemic was about 0.5% to 1% in many locations (including France, Netherlands, New Zealand, and Portugal), 1% to 2% in other locations (Australia, England, Lithuania, and Spain), and exceeded 2% in Italy.<ref name="EJE_levinetal">{{#invoke:cite journal || vauthors = Levin AT, Hanage WP, Owusu-Boaitey N, Cochran KB, Walsh SP, Meyerowitz-Katz G | title = Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications | journal = European Journal of Epidemiology | volume = 35 | issue = 12 | pages = 1123–1138 | date = December 2020 | pmid = 33289900 | pmc = 7721859 | doi = 10.1007/s10654-020-00698-1 | doi-access = free | title-link = doi }} [[File:CC BY icon.svg|50px]] Text was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].</ref> That study also found that most of these differences in IFR reflected corresponding differences in the age composition of the population and age-specific infection rates; in particular, the metaregression estimate of IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85.<ref name="EJE_levinetal" /> These results were also highlighted in a December 2020 report issued by the WHO.<ref>{{#invoke:cite journal||title=Background paper on Covid-19 disease and vaccines: prepared by the Strategic Advisory Group of Experts (SAGE) on immunization working group on COVID-19 vaccines|date=22 December 2020|url=https://apps.who.int/iris/handle/10665/338095|website=World Health Organization|hdl=10665/338095 | author =World Health Organization }}</ref>
{| class="wikitable"
|+{{nowrap|IFR estimate per age group<br />(to December 2020)}}<ref name="EJE_levinetal" />
!Age group
!IFR
|-
|0–34
|0.004%
|-
|35–44
|0.068%
|-
|45–54
|0.23%
|-
|55–64
|0.75%
|-
|65–74
|2.5%
|-
|75–84
|8.5%
|-
|85 +
|28.3%
|}
An analysis of those IFR rates indicates that COVID{{nbhyph}}19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate of COVID-19 is two orders of magnitude greater than the annualised risk of a fatal automobile accident and far more dangerous than seasonal [[Medicine:Influenza|influenza]].<ref name="EJE_levinetal" />

==== Earlier estimates of IFR ====
At an early stage of the pandemic, the World Health Organization reported estimates of IFR between 0.3% and 1%.<ref>{{#invoke:Cite web||title=Coronavirus disease 2019 (COVID-19) Situation Report – 30 |url=https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200219-sitrep-30-covid-19.pdf |access-date=3 June 2020 |date=19 February 2020}}</ref><ref>{{#invoke:Cite web||title=Coronavirus disease 2019 (COVID-19) Situation Report – 31 |url=https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200220-sitrep-31-covid-19.pdf |access-date=23 April 2020 |date=20 February 2020}}</ref> On 2{{spaces}}July, The WHO's chief scientist reported that the average IFR estimate presented at a two-day WHO expert forum was about 0.6%.<ref name="NYT-20200704dm">{{#invoke:cite news || vauthors = McNeil Jr DG |title=The Pandemic's Big Mystery: How Deadly Is the Coronavirus? – Even with more than 500,000 dead worldwide, scientists are struggling to learn how often the virus kills. Here's why |url=https://www.nytimes.com/2020/07/04/health/coronavirus-death-rate.html |archive-url=https://web.archive.org/web/20200704152005/https://www.nytimes.com/2020/07/04/health/coronavirus-death-rate.html |archive-date=4 July 2020 |url-access=subscription |url-status=live |date=4 July 2020 |work={{wipe|The New York Times}} |access-date=6 July 2020}}</ref><ref>{{#invoke:cite news ||title=Global Research and Innovation Forum on COVID-19: Virtual Press Conference |url=https://www.who.int/docs/default-source/coronaviruse/virtual-press-conference---2-july---update-on-covid-19-r-d.pdf |publisher=World Health Organization |date=2 July 2020}}</ref> In August, the WHO found that studies incorporating data from broad serology testing in Europe showed IFR estimates converging at approximately 0.5–1%.<ref>{{#invoke:Cite web||title=Estimating mortality from COVID-19|url=https://www.who.int/news-room/commentaries/detail/estimating-mortality-from-covid-19|access-date=21 September 2020|website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref> Firm lower limits of IFRs have been established in a number of locations such as New York City and Bergamo in Italy since the IFR cannot be less than the population fatality rate. (After sufficient time however, people can get reinfected).<ref>{{#invoke:cite journal|| vauthors = Shaffer C |date=23 October 2021|title=Covid-19 still rife in Iran |journal=New Scientist|volume=252|issue=3357|pages=10–11|doi=10.1016/S0262-4079(21)01865-0|pmid=34720322|issn=0262-4079|pmc=8536311|bibcode=2021NewSc.252...10S}}</ref> As of 10 July, in New York City, with a population of 8.4&nbsp;million, 23,377 individuals (18,758 confirmed and 4,619 probable) have died with COVID‑19 (0.3% of the population).<ref>{{#invoke:Cite web||title=COVID-19: Data |url=https://www1.nyc.gov/site/doh/covid/covid-19-data.page |publisher=City of New York}}</ref> Antibody testing in New York City suggested an IFR of ≈0.9%,<ref>{{#invoke:cite SSRN||title=SARS-CoV-2, COVID-19, Infection Fatality Rate (IFR) Implied by the Serology, Antibody, Testing in New York City| vauthors = Wilson L |date=May 2020|ssrn=3590771}}</ref> and ≈1.4%.<ref>{{#invoke:cite journal || vauthors = Yang W, Kandula S, Huynh M, Greene SK, Van Wye G, Li W, Chan HT, McGibbon E, Yeung A, Olson D, Fine A, Shaman J | display-authors = 6 | title = Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis | journal = The Lancet. Infectious Diseases | volume = 21 | issue = 2 | pages = 203–212 | date = February 2021 | pmid = 33091374 | pmc = 7572090 | doi = 10.1016/s1473-3099(20)30769-6 }}</ref> In Bergamo province, 0.6% of the population has died.<ref>{{#invoke:Cite web||url=https://medium.com/bccp-uc-berkeley/how-deadly-is-covid-19-data-science-offers-answers-from-italy-mortality-data-58abedf824cf|title=How deadly is COVID-19? Data Science offers answers from Italy mortality data.| vauthors = Modi C |date=21 April 2020 |website=Medium |access-date=23 April 2020}}</ref> In September 2020, the U.S. Centers for Disease Control and Prevention (CDC) reported preliminary estimates of age-specific IFRs for public health planning purposes.<ref>{{#invoke:Cite web||title=Coronavirus Disease 2019 (COVID-19) |url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html |website=U.S. Centers for Disease Control and Prevention (CDC) |access-date=9 December 2020 |date=10 September 2020}}</ref>

=== Sex differences ===
{{Main|Social:Gendered impact of the COVID-19 pandemic}}
{| class="wikitable collapsible collapsed" style="margin-left:1em; font-size: 90%; float:right; clear:right"
|-
!colspan="10| Percentage of infected people who are hospitalised
|-
!
! 0–19
! 20–29
! 30–39
! 40–49
! 50–59
! 60–69
! 70–79
! 80+
! Total
|-
! Female
|{{shade|0.1}}<br /><small>(0.07–0.2)</small>
|{{shade|0.5}}<br /><small>(0.3–0.8)</small>
|{{shade|0.9}}<br /><small>(0.5–1.5)</small>
|{{shade|1.3}}<br /><small>(0.7–2.1)</small>
|{{shade|2.6}}<br /><small>(1.5–4.2)</small>
|{{shade|5.1}}<br /><small>(2.9–8.3)</small>
|{{shade|7.8}}<br /><small>(4.4–12.8)</small>
|{{shade|19.3}}<br /><small>(10.9–31.6)</small>
|{{shade|2.6}}<br /><small>(1.5–4.3)</small>
|-
! Male
|{{shade|0.2}}<br /><small>(0.08–0.2)</small>
|{{shade|0.6}}<br /><small>(0.3–0.9)</small>
|{{shade|1.2}}<br /><small>(0.7–1.9)</small>
|{{shade|1.6}}<br /><small>(0.9–2.6)</small>
|{{shade|3.2}}<br /><small>(1.8–5.2)</small>
|{{shade|6.7}}<br /><small>(3.7–10.9)</small>
|{{shade|11.0}}<br /><small>(6.2–17.9)</small>
|{{shade|37.6}}<br /><small>(21.1–61.3)</small>
|{{shade|3.3}}<br /><small>(1.8–5.3)</small>
|-
! Total
|{{shade|0.1}}<br /><small>(0.08–0.2)</small>
|{{shade|0.5}}<br /><small>(0.3–0.8)</small>
|{{shade|1.1}}<br /><small>(0.6–1.7)</small>
|{{shade|1.4}}<br /><small>(0.8–2.3)</small>
|{{shade|2.9}}<br /><small>(1.6–4.7)</small>
|{{shade|5.8}}<br /><small>(3.3–9.5)</small>
|{{shade|9.3}}<br /><small>(5.2–15.1)</small>
|{{shade|26.2}}<br /><small>(14.8–42.7)</small>
|{{shade|2.9}}<br /><small>(1.7–4.8)</small>
|-
!colspan="10| Percentage of hospitalised people who go to Intensive Care Unit
|-
!
! 0–19
! 20–29
! 30–39
! 40–49
! 50–59
! 60–69
! 70–79
! 80+
! Total
|-
! Female
|{{shade|16.7}}<br /><small>(14.3–19.3)</small>
|{{shade|8.7}}<br /><small>(7.5–9.9)</small>
|{{shade|11.9}}<br /><small>(10.9–13.0)</small>
|{{shade|16.6}}<br /><small>(15.6–17.7)</small>
|{{shade|20.7}}<br /><small>(19.8–21.6)</small>
|{{shade|23.1}}<br /><small>(22.2–24.0)</small>
|{{shade|18.7}}<br /><small>(18.0–19.5)</small>
|{{shade|4.2}}<br /><small>(4.0–4.5)</small>
|{{shade|14.3}}<br /><small>(13.9–14.7)</small>
|-
! Male
|{{shade|26.9}}<br /><small>(23.1–31.1)</small>
|{{shade|14.0}}<br /><small>(12.2–16.0)</small>
|{{shade|19.2}}<br /><small>(17.6–20.9)</small>
|{{shade|26.9}}<br /><small>(25.4–28.4)</small>
|{{shade|33.4}}<br /><small>(32.0–34.8)</small>
|{{shade|37.3}}<br /><small>(36.0–38.6)</small>
|{{shade|30.2}}<br /><small>(29.1–31.3)</small>
|{{shade|6.8}}<br /><small>(6.5–7.2)</small>
|{{shade|23.1}}<br /><small>(22.6–23.6)</small>
|-
! Total
|{{shade|22.2}}<br /><small>(19.1–25.7)</small>
|{{shade|11.6}}<br /><small>(10.1–13.2)</small>
|{{shade|15.9}}<br /><small>(14.5–17.3)</small>
|{{shade|22.2}}<br /><small>(21.0–23.5)</small>
|{{shade|27.6}}<br /><small>(26.5–28.7)</small>
|{{shade|30.8}}<br /><small>(29.8–31.8)</small>
|{{shade|24.9}}<br /><small>(24.1–25.8)</small>
|{{shade|5.6}}<br /><small>(5.3–5.9)</small>
|{{shade|19.0}}<br /><small>(18.7–19.44)</small>
|-
!colspan="10| Percent of hospitalised people who die
|-
!
! 0–19
! 20–29
! 30–39
! 40–49
! 50–59
! 60–69
! 70–79
! 80+
! Total
|-
! Female
|{{shade|0.5}}<br /><small>(0.2–1.0)</small>
|{{shade|0.9}}<br /><small>(0.5–1.3)</small>
|{{shade|1.5}}<br /><small>(1.2–1.9)</small>
|{{shade|2.6}}<br /><small>(2.3–3.0)</small>
|{{shade|5.2}}<br /><small>(4.8–5.6)</small>
|{{shade|10.1}}<br /><small>(9.5–10.6)</small>
|{{shade|16.7}}<br /><small>(16.0–17.4)</small>
|{{shade|25.2}}<br /><small>(24.4–26.0)</small>
|{{shade|14.4}}<br /><small>(14.0–14.8)</small>
|-
! Male
|{{shade|0.7}}<br /><small>(0.3–1.5)</small>
|{{shade|1.3}}<br /><small>(0.8–1.9)</small>
|{{shade|2.2}}<br /><small>(1.7–2.7)</small>
|{{shade|3.8}}<br /><small>(3.3–4.4)</small>
|{{shade|7.6}}<br /><small>(7.0–8.2)</small>
|{{shade|14.8}}<br /><small>(14.1–15.6)</small>
|{{shade|24.6}}<br /><small>(23.7–25.6)</small>
|{{shade|37.1}}<br /><small>(36.1–38.2)</small>
|{{shade|21.2}}<br /><small>(20.8–21.7)</small>
|-
! Total
|{{shade|0.6}}<br /><small>(0.2–1.3)</small>
|{{shade|1.1}}<br /><small>(0.7–1.6)</small>
|{{shade|1.9}}<br /><small>(1.5–2.3)</small>
|{{shade|3.3}}<br /><small>(2.9–3.8)</small>
|{{shade|6.5}}<br /><small>(6.0–7.0)</small>
|{{shade|12.6}}<br /><small>(12.0–13.2)</small>
|{{shade|21.0}}<br /><small>(20.3–21.7)</small>
|{{shade|31.6}}<br /><small>(30.9–32.4)</small>
|{{shade|18.1}}<br /><small>(17.8–18.4)</small>
|-
!colspan="10| Percent of infected people who die{{snd}}infection fatality rate (IFR)
|-
!
! 0–19
! 20–29
! 30–39
! 40–49
! 50–59
! 60–69
! 70–79
! 80+
! Total
|-
! Female
|{{shade|0.001}}<br /><small>(<0.001–0.002)</small>
|{{shade|0.004}}<br /><small>(0.002–0.007)</small>
|{{shade|0.01}}<br /><small>(0.007–0.02)</small>
|{{shade|0.03}}<br /><small>(0.02–0.06)</small>
|{{shade|0.1}}<br /><small>(0.08–0.2)</small>
|{{shade|0.5}}<br /><small>(0.3–0.8)</small>
|{{shade|1.3}}<br /><small>(0.7–2.1)</small>
|{{shade|4.9}}<br /><small>(2.7–8.0)</small>
|{{shade|0.4}}<br /><small>(0.2–0.6)</small>
|-
! Male
|{{shade|0.001}}<br /><small>(<0.001–0.003)</small>
|{{shade|0.007}}<br /><small>(0.003–0.01)</small>
|{{shade|0.03}}<br /><small>(0.02–0.05)</small>
|{{shade|0.06}}<br /><small>(0.03–0.1)</small>
|{{shade|0.2}}<br /><small>(0.1–0.4)</small>
|{{shade|1.0}}<br /><small>(0.6–1.6)</small>
|{{shade|2.7}}<br /><small>(1.5–1.4)</small>
|{{shade|14.0}}<br /><small>(7.9–22.7)</small>
|{{shade|0.7}}<br /><small>(0.4–1.1)</small>
|-
! Total
|{{shade|0.001}}<br /><small>(<0.001–0.002)</small>
|{{shade|0.005}}<br /><small>(0.003–0.01)</small>
|{{shade|0.02}}<br /><small>(0.01–0.03)</small>
|{{shade|0.05}}<br /><small>(0.03–0.08)</small>
|{{shade|0.2}}<br /><small>(0.1–0.3)</small>
|{{shade|0.7}}<br /><small>(0.4–1.2)</small>
|{{shade|1.9}}<br /><small>(1.1–3.2)</small>
|{{shade|8.3}}<br /><small>(4.7–13.5)</small>
|{{shade|0.5}}<br /><small>(0.3–0.9)</small>
|-
|colspan=10| Numbers in parentheses are 95% [[Credible interval|credible interval]]s for the estimates.
|}

COVID‑19 [[Medicine:Case fatality rate|case fatality rate]]s are higher among men than women in most countries. However, in a few countries like India, Nepal, Vietnam, and Slovenia the fatality cases are higher in women than men.<ref name="Dehingia-2021" /> Globally, men are more likely to be admitted to the [[Medicine:Intensive care unit|ICU]] and more likely to die.<ref>{{#invoke:Cite web|| vauthors = McIntosh K |title=Covid 19 Clinical Features|url=https://www.uptodate.com/contents/covid-19-clinical-features|access-date=12 May 2021|website=[[Medicine:UpToDate|UpToDate]]|publication-date=April 2021}}</ref><ref>{{#invoke:cite journal || vauthors = Peckham H, de Gruijter NM, Raine C, Radziszewska A, Ciurtin C, Wedderburn LR, Rosser EC, Webb K, Deakin CT | display-authors = 6 | title = Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission | journal = Nature Communications | volume = 11 | issue = 1 | pages = 6317 | date = December 2020 | pmid = 33298944 | doi = 10.1038/s41467-020-19741-6 | pmc = 7726563 | bibcode = 2020NatCo..11.6317P }}</ref> One meta-analysis found that globally, men were more likely to get COVID‑19 than women; there were approximately 55 men and 45 women per 100 infections ([[Confidence interval|CI]]: 51.43–56.58).<ref>{{#invoke:cite journal || vauthors = Abate BB, Kassie AM, Kassaw MW, Aragie TG, Masresha SA | title = Sex difference in coronavirus disease (COVID-19): a systematic review and meta-analysis | journal = BMJ Open | volume = 10 | issue = 10 | pages = e040129 | date = October 2020 | pmid = 33028563 | doi = 10.1136/bmjopen-2020-040129 | pmc = 7539579 }}</ref>

The [[Organization:Chinese Center for Disease Control and Prevention|Chinese Center for Disease Control and Prevention]] reported the death rate was 2.8% for men and 1.7% for women.<ref name="Epidemiology17Feb2020"/> Later reviews in June 2020 indicated that there is no significant difference in susceptibility or in CFR between genders.<ref>{{#invoke:cite journal || vauthors = Hu Y, Sun J, Dai Z, Deng H, Li X, Huang Q, Wu Y, Sun L, Xu Y | display-authors = 6 | title = Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis | journal = Journal of Clinical Virology | volume = 127 | pages = 104371 | date = June 2020 | pmid = 32315817 | pmc = 7195434 | doi = 10.1016/j.jcv.2020.104371 }}</ref><ref>{{#invoke:cite journal || vauthors = Fu L, Wang B, Yuan T, Chen X, Ao Y, Fitzpatrick T, Li P, Zhou Y, Lin YF, Duan Q, Luo G, Fan S, Lu Y, Feng A, Zhan Y, Liang B, Cai W, Zhang L, Du X, Li L, Shu Y, Zou H | display-authors = 6 | title = Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis | journal = The Journal of Infection | volume = 80 | issue = 6 | pages = 656–665 | date = June 2020 | pmid = 32283155 | pmc = 7151416 | doi = 10.1016/j.jinf.2020.03.041 }}</ref> One review acknowledges the different mortality rates in Chinese men, suggesting that it may be attributable to lifestyle choices such as smoking and drinking alcohol rather than genetic factors.<ref>{{#invoke:cite journal || vauthors = Yuki K, Fujiogi M, Koutsogiannaki S | title = COVID-19 pathophysiology: A review | journal = Clinical Immunology | volume = 215 | pages = 108427 | date = June 2020 | pmid = 32325252 | pmc = 7169933 | doi = 10.1016/j.clim.2020.108427 | s2cid = 216028003 }}</ref> Smoking, which in some countries like China is mainly a male activity, is a habit that contributes to increasing significantly the case fatality rates among men.<ref name="Dehingia-2021" /> Sex-based immunological differences, lesser prevalence of smoking in women and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men.<ref name="nyt-italy">{{#invoke:cite news || vauthors = Rabin RC | title = In Italy, Coronavirus Takes a Higher Toll on Men |url=https://www.nytimes.com/2020/03/20/health/coronavirus-italy-men-risk.html |archive-url=https://web.archive.org/web/20200320214013/https://www.nytimes.com/2020/03/20/health/coronavirus-italy-men-risk.html |archive-date=20 March 2020 |url-access=subscription |url-status=live |access-date=7 April 2020 |work=The New York Times |date=20 March 2020}}</ref> In Europe as of February 2020, 57% of the infected people were men and 72% of those died with COVID‑19 were men.<ref>{{#invoke:Cite web||title=COVID-19 weekly surveillance report |url=https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/weekly-surveillance-report |archive-url=https://web.archive.org/web/20200315074508/https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/weekly-surveillance-report |url-status=dead |archive-date=15 March 2020 |website=[[Organization:World Health Organization|World Health Organization]] (WHO) |access-date=7 April 2020}}</ref> As of April 2020, the US government is not tracking sex-related data of COVID‑19 infections.<ref name="nytimesus">{{#invoke:cite news || vauthors = Gupta AH | title = Does Covid-19 Hit Women and Men Differently? U.S. Isn't Keeping Track |url=https://www.nytimes.com/2020/04/03/us/coronavirus-male-female-data-bias.html |archive-url=https://web.archive.org/web/20200403135013/https://www.nytimes.com/2020/04/03/us/coronavirus-male-female-data-bias.html |archive-date=3 April 2020 |url-access=subscription |url-status=live |access-date=7 April 2020 |work=The New York Times |date=3 April 2020}}</ref> Research has shown that viral illnesses like Ebola, HIV, influenza and SARS affect men and women differently.<ref name="nytimesus" />

=== Ethnic differences ===
In the US, a greater proportion of deaths due to COVID‑19 have occurred among African Americans and other minority groups.<ref name="AVD">{{#invoke:cite journal || vauthors = Dorn AV, Cooney RE, Sabin ML | title = COVID-19 exacerbating inequalities in the US | journal = Lancet | volume = 395 | issue = 10232 | pages = 1243–1244 | date = April 2020 | pmid = 32305087 | pmc = 7162639 | doi = 10.1016/S0140-6736(20)30893-X }}</ref> Structural factors that prevent them from practising social distancing include their concentration in crowded substandard housing and in "essential" occupations such as retail grocery workers, public transit employees, health-care workers and custodial staff. Greater prevalence of lacking health insurance and care of underlying conditions such as [[Medicine:Diabetes|diabetes]],<ref name="Shauly-Aharonov-2021">{{#invoke:cite journal ||last1=Shauly-Aharonov |first1=Michal |last2=Shafrir |first2=Asher |last3=Paltiel |first3=Ora |last4=Calderon-Margalit |first4=Ronit |last5=Safadi |first5=Rifaat |last6=Bicher |first6=Roee |last7=Barenholz-Goultschin |first7=Orit |last8=Stokar |first8=Joshua |date=22 July 2021 |title=Both high and low pre-infection glucose levels associated with increased risk for severe COVID-19: New insights from a population-based study |journal=PLOS ONE |volume=16 |issue=7 |pages=e0254847 |doi=10.1371/journal.pone.0254847 |issn=1932-6203 |pmc=8297851 |pmid=34293038|bibcode=2021PLoSO..1654847S |doi-access=free }}</ref> hypertension, and heart disease also increase their risk of death.<ref>{{#invoke:cite journal || vauthors = Adams ML, Katz DL, Grandpre J | title = Population-Based Estimates of Chronic Conditions Affecting Risk for Complications from Coronavirus Disease, United States | journal = Emerging Infectious Diseases | volume = 26 | issue = 8 | pages = 1831–1833 | date = August 2020 | pmid = 32324118 | pmc = 7392427 | doi = 10.3201/eid2608.200679 | title-link = doi | doi-access = free }}</ref> Similar issues affect Native American and Latino communities.<ref name="AVD" /> On the one hand, in the Dominican Republic there is a clear example of both gender and ethnic inequality. In this Latin American territory, there is great inequality and precariousness that especially affects Dominican women, with greater emphasis on those of Haitian descent.<ref name="Batthyany-2020">{{#invoke:Cite web|| vauthors = Batthyány K |title=Coronavirus y Desigualdades preexistentes: Género y Cuidados|url=https://www.clacso.org/coronavirus-y-desigualdades-preexistentes-genero-y-cuidados/|access-date=22 April 2021|website=CLACSO (Consejo Latinoamericano de Ciencias Sociales)|date=13 October 2020}}</ref> According to a US health policy non-profit, 34% of American Indian and Alaska Native People (AIAN) non-elderly adults are at risk of serious illness compared to 21% of white non-elderly adults.<ref>{{#invoke:Cite web||url=https://www.kff.org/coronavirus-covid-19/issue-brief/covid-19-presents-significant-risks-for-american-indian-and-alaska-native-people/|title=COVID-19 Presents Significant Risks for American Indian and Alaska Native People|date=14 May 2020}}</ref> The source attributes it to disproportionately high rates of many health conditions that may put them at higher risk as well as living conditions like lack of access to clean water.<ref>{{#invoke:Cite web||title=COVID-19 Presents Significant Risks for American Indian and Alaska Native People|url=https://www.kff.org/coronavirus-covid-19/issue-brief/covid-19-presents-significant-risks-for-american-indian-and-alaska-native-people/|date=14 May 2020}}</ref>

Leaders have called for efforts to research and address the disparities.<ref>{{#invoke:cite journal || vauthors = Laurencin CT, McClinton A | title = The COVID-19 Pandemic: a Call to Action to Identify and Address Racial and Ethnic Disparities | journal = Journal of Racial and Ethnic Health Disparities | volume = 7 | issue = 3 | pages = 398–402 | date = June 2020 | pmid = 32306369 | pmc = 7166096 | doi = 10.1007/s40615-020-00756-0 }}</ref> In the UK, a greater proportion of deaths due to COVID‑19 have occurred in those of a Black, Asian, and other ethnic minority background.<ref>{{#invoke:Cite web||date=9 June 2020|title=How coronavirus deaths in the UK compare by race and ethnicity|url=https://www.independent.co.uk/news/uk/home-news/coronavirus-death-toll-uk-race-white-black-asian-bame-ethnicity-cases-a9557076.html|access-date=10 June 2020|website=The Independent}}</ref><ref>{{#invoke:Cite web||title=Emerging findings on the impact of COVID-19 on black and minority ethnic people|url=https://www.health.org.uk/news-and-comment/charts-and-infographics/emerging-findings-on-the-impact-of-covid-19-on-black-and-min|access-date=10 June 2020|publisher=The Health Foundation}}</ref><ref>{{#invoke:cite news || vauthors = Butcher B, Massey J |date=9 June 2020|title=Why are more BAME people dying from coronavirus?|work=BBC News |url=https://www.bbc.com/news/uk-52219070 |access-date=10 June 2020}}</ref> More severe impacts upon patients including the relative incidence of the necessity of hospitalisation requirements, and vulnerability to the disease has been associated via DNA analysis to be expressed in genetic variants at chromosomal region 3, features that are associated with European [[Biology:Neanderthal|Neanderthal]] heritage. That structure imposes greater risks that those affected will develop a more severe form of the disease.<ref name=Neanderthal>{{#invoke:Cite web|| title=The ancient Neanderthal hand in severe COVID-19 | website=ScienceDaily | date=30 September 2020 | url=https://www.sciencedaily.com/releases/2020/09/200930094758.htm | access-date=13 December 2020}}</ref> The findings are from Professor Svante Pääbo and researchers he leads at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institutet.<ref name=Neanderthal /> This admixture of modern human and Neanderthal genes is estimated to have occurred roughly between 50,000 and 60,000 years ago in Southern Europe.<ref name=Neanderthal />

=== Comorbidities ===
[[Biology:Biology|Biological]] factors (immune response) and the general behaviour (habits) can strongly determine the consequences of COVID‑19.<ref name="Dehingia-2021" /> Most of those who die of COVID‑19 have pre-existing (underlying) conditions, including hypertension, [[Medicine:Diabetes mellitus|diabetes mellitus]],<ref name="Shauly-Aharonov-2021" /> and [[Medicine:Cardiovascular disease|cardiovascular disease]].<ref name="WHO-2020a">{{#invoke:Cite web||url=https://www.who.int/dg/speeches/detail/who-director-general-s-statement-on-the-advice-of-the-ihr-emergency-committee-on-novel-coronavirus |title=WHO Director-General's statement on the advice of the IHR Emergency Committee on Novel Coronavirus |website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref> According to March data from the United States, 89% of those hospitalised had preexisting conditions.<ref>{{#invoke:cite journal || vauthors = Garg S, Kim L, Whitaker M, O'Halloran A, Cummings C, Holstein R, Prill M, Chai SJ, Kirley PD, Alden NB, Kawasaki B, Yousey-Hindes K, Niccolai L, Anderson EJ, Openo KP, Weigel A, Monroe ML, Ryan P, Henderson J, Kim S, Como-Sabetti K, Lynfield R, Sosin D, Torres S, Muse A, Bennett NM, Billing L, Sutton M, West N, Schaffner W, Talbot HK, Aquino C, George A, Budd A, Brammer L, Langley G, Hall AJ, Fry A | display-authors = 6 | title = Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 – COVID-NET, 14 States, March 1–30, 2020 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 69 | issue = 15 | pages = 458–464 | date = April 2020 | pmid = 32298251 | pmc = 7755063 | doi = 10.15585/mmwr.mm6915e3 | title-link = doi | doi-access = free }}</ref> The Italian Istituto Superiore di Sanità reported that out of 8.8% of deaths where [[Medicine:Medical record|medical charts]] were available, 96.1% of people had at least one [[Medicine:Comorbidity|comorbidity]] with the average person having 3.4 diseases.<ref name="ISSCharacteristics">{{#invoke:cite report||url=https://www.epicentro.iss.it/en/coronavirus/bollettino/Report-COVID-2019_22_July_2020.pdf|title=Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on July 22nd, 2020|date=22 July 2020|publisher=[[Organization:Istituto Superiore di Sanità|Istituto Superiore di Sanità]]|access-date=4 October 2020|vauthors=Palmieri L, Andrianou X, Barbariol P, Bella A, Bellino S, Benelli E, Bertinato L, Boros S, Brambilla G, Calcagnini G, Canevelli M, Castrucci MR, Censi F, Ciervo A, Colaizzo E, D'Ancona F, Del Manso M, Donfrancesco C, Fabiani M, Filia A, Floridia M, Giuliano M, Grisetti T, Langer M, Lega I, Lo Noce C, Maiozzi P, Malchiodi Albedi F, Manno V, Martini M, Mateo Urdiales A, Mattei E, Meduri C, Meli P, Minelli G, Nebuloni M, Nisticò L, Nonis M, Onder G, Palmisano L, Petrosillo N, Pezzotti P, Pricci F, Punzo O, Puro V, Raparelli V, Rezza G, Riccardo F, Rota MC, Salerno P, Serra D, Siddu A, Stefanelli P, Tamburo De Bella M, Tiple D, Unim B, Vaianella L, Vanacore N, Vichi M, Villani ER, Brusaferro S|display-authors=6}}</ref> According to this report the most common comorbidities are hypertension (66% of deaths), type&nbsp;2 diabetes (29.8% of deaths), ischaemic heart disease (27.6% of deaths), [[Medicine:Atrial fibrillation|atrial fibrillation]] (23.1% of deaths) and chronic renal failure (20.2% of deaths).

Most critical respiratory comorbidities according to the US Centers for Disease Control and Prevention (CDC), are: moderate or severe [[Medicine:Asthma|asthma]], pre-existing [[Medicine:Chronic obstructive pulmonary disease|COPD]], [[Medicine:Pulmonary fibrosis|pulmonary fibrosis]], [[Medicine:Cystic fibrosis|cystic fibrosis]].<ref>{{#invoke:Cite web||date=11 February 2020|title=Coronavirus Disease 2019 (COVID-19)|url=https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.html|access-date=19 June 2020|website=U.S. Centers for Disease Control and Prevention (CDC) }}</ref> Evidence stemming from [[Meta-analysis|meta-analysis]] of several smaller research papers also suggests that smoking can be associated with worse outcomes.<ref>{{#invoke:cite journal || vauthors = Zhao Q, Meng M, Kumar R, Wu Y, Huang J, Lian N, Deng Y, Lin S | display-authors = 6 | title = The impact of COPD and smoking history on the severity of COVID-19: A systemic review and meta-analysis | journal = Journal of Medical Virology | volume = 92 | issue = 10 | pages = 1915–1921 | date = October 2020 | pmid = 32293753 | pmc = 7262275 | doi = 10.1002/jmv.25889 }}</ref><ref>{{#invoke:Cite web||title=Smoking and COVID-19|url=https://www.who.int/news-room/commentaries/detail/smoking-and-covid-19|access-date=19 June 2020|website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref> When someone with existing respiratory problems is infected with COVID‑19, they might be at greater risk for severe symptoms.<ref>{{#invoke:Cite web||title=Coronavirus Disease 2019 (COVID-19)|url=https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.html|date=11 February 2020|website=U.S. Centers for Disease Control and Prevention (CDC) |access-date=4 May 2020}}</ref> COVID‑19 also poses a greater risk to people who [[Medicine:Opioid use disorder|misuse opioids]] and amphetamines, insofar as their drug use may have caused lung damage.<ref>{{#invoke:Cite web||title=People who use drugs are more vulnerable to coronavirus. Here's what clinics are doing to help.|url=https://www.theadvocate.com/baton_rouge/news/coronavirus/article_f80cf77e-84fa-11ea-88d5-2b37dc9dd966.html| vauthors = DeRobertis J |date=3 May 2020|website=The Advocate (Louisiana)|access-date=4 May 2020}}</ref>

In August 2020, the CDC issued a caution that [[Medicine:Tuberculosis|tuberculosis]] (TB) infections could increase the risk of severe illness or death. The WHO recommended that people with respiratory symptoms be screened for both diseases, as testing positive for COVID‑19 could not rule out co-infections. Some projections have estimated that reduced TB detection due to the pandemic could result in 6.3&nbsp;million additional TB cases and 1.4&nbsp;million TB-related deaths by 2025.<ref>{{#invoke:Cite web||url=https://www.cdc.gov/coronavirus/2019-ncov/global-covid-19/TB-non-us-settings.html|title=Coronavirus Disease 2019 (COVID-19)|date=11 February 2020|website=U.S. Centers for Disease Control and Prevention (CDC) }}</ref>

== History ==
The virus is thought to be of natural animal origin, most likely through [[Biology:Spillover infection|spillover infection]].<ref name="NM-20200317">{{#invoke:cite journal || vauthors = Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF | title = The proximal origin of SARS-CoV-2 | journal = Nature Medicine | volume = 26 | issue = 4 | pages = 450–452 | date = April 2020 | pmid = 32284615 | pmc = 7095063 | doi = 10.1038/s41591-020-0820-9 }}</ref><ref name="PMC7969828">{{#invoke:cite journal || vauthors = Frutos R, Gavotte L, Devaux CA | title = Understanding the origin of COVID-19 requires to change the paradigm on zoonotic emergence from the spillover to the circulation model | journal = Infection, Genetics and Evolution | volume = 95 | pages = 104812 | date = November 2021 | pmid = 33744401 | pmc = 7969828 | doi = 10.1016/j.meegid.2021.104812 }}</ref><ref>{{#invoke:cite journal || vauthors = Holmes EC, Goldstein SA, Rasmussen AL, Robertson DL, Crits-Christoph A, Wertheim JO, Anthony SJ, Barclay WS, Boni MF, Doherty PC, Farrar J, Geoghegan JL, Jiang X, Leibowitz JL, Neil SJ, Skern T, Weiss SR, Worobey M, Andersen KG, Garry RF, Rambaut A | display-authors = 6 | title = The origins of SARS-CoV-2: A critical review | journal = Cell | volume = 184 | issue = 19 | pages = 4848–4856 | date = September 2021 | pmid = 34480864 | pmc = 8373617 | doi = 10.1016/j.cell.2021.08.017 }}</ref> A joint-study conducted in early 2021 by the People's Republic of China and the [[Organization:World Health Organization|World Health Organization]] indicated that the virus descended from a coronavirus that infects wild bats, and likely spread to humans through an intermediary wildlife host.<ref>{{#invoke:Cite web||url=https://www.who.int/publications/i/item/who-convened-global-study-of-origins-of-sars-cov-2-china-part|work=[[Organization:World Health Organization|World Health Organization]]|title=WHO-convened Global Study of Origins of SARS-CoV-2: China Part|date=30 March 2021|access-date=29 July 2022}}</ref> There are several theories about where the [[Medicine:Index case|index case]] originated and investigations into the origin of the pandemic are ongoing.<ref name="patientZero">{{#invoke:cite news|| vauthors = Duarte F | date=24 February 2020|title=As the cases of coronavirus increase in China and around the world, the hunt is on to identify "patient zero".|work=BBC News|url=https://www.bbc.com/future/article/20200221-coronavirus-the-harmful-hunt-for-covid-19s-patient-zero|access-date=22 March 2020}}</ref> According to articles published in July 2022 in ''Science'', virus transmission into humans occurred through two spillover events in November 2019 and was likely due to live wildlife trade on the Huanan wet market in the city of [[Place:Wuhan|Wuhan]] (Hubei, China).<ref>{{#invoke:cite journal||title=The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2 |date=26 July 2022 |journal=Science|display-authors=6|vauthors=Pekar JE, Magee P, Parker E, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee JM, Park H, Park MS, Ching ZY, Lin TP, Isa NM, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO|pages=960–966 |doi-access = free | title-link = doi |volume=377 |issue=6609 |doi=10.1126/science.abp8337|pmid=35881005 |pmc=9348752 |bibcode=2022Sci...377..960P }}</ref><ref>{{Cite news |last=Gill |first=Victoria |date=26 July 2022 |title=Covid origin studies say evidence points to Wuhan market |work=BBC News Online |publisher=BBC |url=https://www.bbc.com/news/science-environment-62307383 |url-status=live |access-date=31 August 2023 |archive-url=https://web.archive.org/web/20220726153445/https://www.bbc.com/news/science-environment-62307383 |archive-date=26 July 2022}}</ref><ref>{{#invoke:cite journal ||title=The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic |date=July 2022 |journal=Science |doi=10.1126/science.abp8715 | vauthors = Worobey M, Levy JI, Serrano LM, Crits-Christoph A, Pekar JE, Goldstein SA, Rasmussen AL, Kraemer MU, Newman C, Koopmans MP, Suchard MA, Wertheim JO, Lemey P, Robertson DL, Garry RF, Holmes EC, Rambaut A, Andersen KG | display-authors=6 | title-link=doi |volume=377 |issue=6609 |pages=951–959 |pmid=35881010 |pmc=9348750 |bibcode=2022Sci...377..951W |s2cid=251067542 }}</ref> Doubts about the conclusions have mostly centered on the precise site of spillover.<ref>{{#invoke:cite news ||url=https://www.nationalgeographic.com/magazine/article/debate-deepens-over-wuhan-wet-markets-role-in-kickstarting-the-pandemic |title=Debate deepens over Wuhan wet market's role in kickstarting the pandemic |date=27 July 2022 |work=National Geographic}}</ref> Earlier [[Biology:Phylogenetics|phylogenetics]] estimated that SARS-CoV-2 arose in October or November 2019.<ref name="evolutionary">{{#invoke:cite journal || vauthors = Li X, Zai J, Zhao Q, Nie Q, Li Y, Foley BT, Chaillon A | display-authors = 6 | title = Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2 | journal = Journal of Medical Virology | volume = 92 | issue = 6 | pages = 602–611 | date = June 2020 | pmid = 32104911 | pmc = 7228310 | doi = 10.1002/jmv.25731 }}</ref><ref name="zoonotic">{{#invoke:cite journal || vauthors = Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF | title = The proximal origin of SARS-CoV-2 | journal = Nature Medicine | volume = 26 | issue = 4 | pages = 450–452 | date = April 2020 | pmid = 32284615 | pmc = 7095063 | doi = 10.1038/s41591-020-0820-9 | title-link = doi | doi-access = free }}</ref><ref name="dorp_evo">{{#invoke:cite journal || vauthors = van Dorp L, Acman M, Richard D, Shaw LP, Ford CE, Ormond L, Owen CJ, Pang J, Tan CC, Boshier FA, Ortiz AT, Balloux F | display-authors = 6 | title = Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 | journal = Infection, Genetics and Evolution | volume = 83 | pages = 104351 | date = September 2020 | pmid = 32387564 | pmc = 7199730 | doi = 10.1016/j.meegid.2020.104351 }}</ref> A phylogenetic algorithm analysis suggested that the virus may have been circulating in Guangdong before Wuhan.<ref>{{#invoke:cite news || vauthors = Grose TK
|url= https://www.usnews.com/news/best-countries/articles/2020-05-13/scientist-suggests-coronavirus-originated-outside-of-wuhan |title=Did the Coronavirus Originate Outside of Wuhan? |work=U.S. News & World Report |date=13 May 2020}}</ref>

Most scientists believe the virus spilled into human populations through natural [[Biology:Zoonosis|zoonosis]], similar to the [[Biology:SARS-CoV-1|SARS-CoV-1]] and [[Biology:MERS-CoV|MERS-CoV]] outbreaks, and consistent with other pandemics in human history.<ref name="pekar">{{#invoke:cite journal ||last1=Pekar |first1=Jonathan |title=The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2 |journal=Science |date=26 July 2022 |volume=377 |issue=6609 |pages=960–966 |doi=10.1126/science.abp8337 |pmid=35881005 |pmc=9348752 |bibcode=2022Sci...377..960P }}</ref><ref name="jiang_wang">{{#invoke:cite journal ||last1=Jiang |first1=Xiaowei |last2=Wang |first2=Ruoqi |title=Wildlife trade is likely the source of SARS-CoV-2 |journal=Science |date=25 August 2022 |volume=377 |issue=6609 |pages=925–926 |doi=10.1126/science.add8384 |pmid=36007033 |bibcode=2022Sci...377..925J |s2cid=251843410 |url=https://www.science.org/doi/10.1126/science.add8384 |access-date=20 November 2022}}</ref> According to the [[Organization:Intergovernmental Panel on Climate Change|Intergovernmental Panel on Climate Change]] several social and environmental factors including [[Earth:Climate change|climate change]], natural ecosystem destruction and [[Biology:Wildlife trade and zoonoses|wildlife trade]] increased the likelihood of such [[Biology:Zoonosis|zoonotic spillover]].<ref>{{#invoke:cite book ||title=Terrestrial and Freshwater Ecosystems and Their Services. In: Climate Change 2022: Impacts, Adaptation and Vulnerability. Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change |date=2022 |publisher=IPCC |pages=233–235 |url=https://www.ipcc.ch/report/ar6/wg2/downloads/report/IPCC_AR6_WGII_Chapter02.pdf |access-date=14 March 2023}}</ref><ref>{{#invoke:cite book ||title=Health, Wellbeing, and the Changing Structure of Communities. In: Climate Change 2022: Impacts, Adaptation and Vulnerability. Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change |date=2022 |publisher=IPCC |pages=1067–1070 |url=https://www.ipcc.ch/report/ar6/wg2/downloads/report/IPCC_AR6_WGII_Chapter07.pdf |access-date=14 March 2023}}</ref> One study made with the support of the [[Social:European Union|European Union]] found [[Earth:Climate change|climate change]] increased the likelihood of the pandemic by influencing distribution of bat species.<ref>{{#invoke:cite web ||title=Climate change may have driven the emergence of SARS-CoV-2 |url=https://www.cam.ac.uk/research/news/climate-change-may-have-driven-the-emergence-of-sars-cov-2 |website=University of Cambridge |date=5 February 2021 |publisher=Science of the Total Environment |access-date=14 March 2023}}</ref><ref>{{#invoke:cite web ||title=Climate change the culprit in the COVID-19 pandemic |url=https://cordis.europa.eu/article/id/430229-climate-change-the-culprit-in-the-covid-19-pandemic |website=European Commission |access-date=24 March 2023}}</ref>

Available evidence suggests that the SARS-CoV-2 virus was originally harboured by bats, and spread to humans multiple times from infected wild animals at the Huanan Seafood Market in [[Place:Wuhan|Wuhan]] in December 2019.<ref name="pekar" /><ref name="jiang_wang" /> A minority of scientists and some members of the U.S intelligence community believe the virus may have been unintentionally leaked from a laboratory such as the [[Organization:Wuhan Institute of Virology|Wuhan Institute of Virology]].<ref name="NYT_DoE_Feb2023">{{#invoke:cite web ||last1=Barnes |first1=Julian E. |title=Lab Leak Most Likely Caused Pandemic, Energy Dept. Says |url=https://www.nytimes.com/2023/02/26/us/politics/china-lab-leak-coronavirus-pandemic.html |website=The New York Times |access-date=27 February 2023 |date=26 February 2023}}</ref><ref name="Hill_Feb_2023_DoE">{{#invoke:cite news ||last1=Mueller |first1=Julia |title=Energy Department's COVID lab leak conclusion: What we know |url=https://thehill.com/policy/healthcare/3874965-what-we-know-about-energy-departments-lab-leak-conclusion/ |access-date=26 March 2023 |work=The Hill |date=26 February 2023}}</ref> The US intelligence community has mixed views on the issue,<ref name="CNN_Feb2023_LeBlanc">{{#invoke:cite news ||last1=LeBlanc |first1=Paul |title=New assessment on the origins of Covid-19 adds to the confusion {{!}} CNN Politics |url=https://www.cnn.com/2023/02/27/politics/covid-origins-doe-assessment-what-matters/index.html |access-date=27 February 2023 |work=CNN |date=27 February 2023 |language=en}}</ref><ref name="Guardian_Feb2023">{{#invoke:cite news ||last1=Davis |first1=Nicola |last2=Hawkins |first2=Amy |title=How seriously should we take the US DoE's Covid lab leak theory? |url=https://www.theguardian.com/world/2023/feb/27/how-seriously-should-we-take-the-us-does-covid-lab-leak-theory |access-date=27 February 2023 |work=The Guardian |date=27 February 2023}}</ref> but overall agrees with the scientific consensus that the virus was not developed as a biological weapon and is unlikely to have been [[Biology:Genetic engineering|genetically engineered]].<ref>{{#invoke:Cite web|| vauthors = Wolf ZB |title=Analysis: Why scientists are suddenly more interested in the lab-leak theory of Covid's origin |url=https://www.cnn.com/2021/05/25/politics/wuhan-lab-covid-origin-theory/index.html|access-date=26 May 2021 |publisher=CNN|date=25 May 2021}}</ref><ref>{{#invoke:cite journal ||vauthors=Maxmen A |title=US COVID origins report: researchers pleased with scientific approach |journal=Nature |volume=597 |issue=7875 |pages=159–160 |date=September 2021 |pmid=34465917 |doi=10.1038/d41586-021-02366-0 |s2cid=237373547 |bibcode=2021Natur.597..159M}}</ref><ref>{{#invoke:Cite news||url=https://www.politico.com/newsletters/future-pulse/2022/11/04/cross-examining-the-lab-leak-theorists-00065103|title=Cross-examining the lab-leak theorists|date=4 November 2022|work=Politico |vauthors=Paun C, Zeller S, Reader R, Leonard B, Scullion G | access-date=21 November 2022 }}</ref><ref>{{#invoke:Cite news||url=https://www.reuters.com/world/us-intelligence-releases-report-covid-19-origins-2021-10-29/|title=U.S. spy agencies say origins of COVID-19 may never be known |vauthors=Hosenball M, Zengerle P|date=30 October 2021 |work={{wipe|Reuters}}|access-date=21 November 2022}}</ref> There is no evidence SARS-CoV-2 existed in any laboratory prior to the pandemic.<ref name=critical>{{#invoke:cite journal ||vauthors=Holmes EC, Goldstein SA, Rasmussen AL, Robertson DL, Crits-Christoph A, Wertheim JO, Anthony SJ, Barclay WS, Boni MF, Doherty PC, Farrar J, Geoghegan JL, Jiang X, Leibowitz JL, Neil SJ, Skern T, Weiss SR, Worobey M, Andersen KG, Garry RF, Rambaut A |title=The origins of SARS-CoV-2: A critical review |journal=Cell |volume=184 |issue=19 |pages=4848–4856 |date=September 2021 |pmid=34480864 |pmc=8373617 |doi=10.1016/j.cell.2021.08.017 |type=Review |display-authors=5 |quote=Under any laboratory escape scenario, SARS-CoV-2 would have to have been present in a laboratory prior to the pandemic, yet no evidence exists to support such a notion and no sequence has been identified that could have served as a precursor.}}</ref><ref name="Gorski">{{#invoke:cite web ||last=Gorski |first=David |date=31 May 2021 |title=The origin of SARS-CoV-2, revisited |url=https://sciencebasedmedicine.org/the-origin-of-sars-cov-2-revisited/ |url-status=live |archive-url=https://web.archive.org/web/20210601072923/https://sciencebasedmedicine.org/the-origin-of-sars-cov-2-revisited/ |archive-date=1 June 2021 |access-date=19 July 2021 |publisher=[[Medicine:Science-Based Medicine|Science-Based Medicine]] |quote=The second [version of the lab leak] is the version that "reasonable" people consider plausible, but there is no good evidence for either version.}}</ref><ref name="HolmesConversationDead">{{#invoke:cite web ||last=Holmes |first=Edward C. |date=14 August 2022 |title=The COVID lab leak theory is dead. Here's how we know the virus came from a Wuhan market |url=http://theconversation.com/the-covid-lab-leak-theory-is-dead-heres-how-we-know-the-virus-came-from-a-wuhan-market-188163 |access-date=4 September 2022 |website=The Conversation |language=en |quote=For the lab leak theory to be true, SARS-CoV-2 must have been present in the Wuhan Institute of Virology before the pandemic started. This would convince me. But the inconvenient truth is there's not a single piece of data suggesting this. There's no evidence for a genome sequence or isolate of a precursor virus at the Wuhan Institute of Virology. Not from gene sequence databases, scientific publications, annual reports, student theses, social media, or emails. Even the intelligence community has found nothing. Nothing. And there was no reason to keep any work on a SARS-CoV-2 ancestor secret before the pandemic.}}</ref>

The first confirmed human infections were in Wuhan. A study of the first 41 cases of confirmed COVID‑19, published in January 2020 in ''The Lancet'', reported the earliest date of onset of symptoms as 1{{spaces}}December 2019.<ref name="WuMarch2020">{{#invoke:cite journal ||vauthors=Wu YC, Chen CS, Chan YJ |title=The outbreak of COVID-19: An overview |journal=Journal of the Chinese Medical Association |volume=83 |issue=3 |pages=217–220 |date=March 2020 |pmid=32134861 |pmc=7153464 |doi=10.1097/JCMA.0000000000000270}}</ref><ref name="Wang24Jan2020">{{#invoke:cite journal ||vauthors=Wang C, Horby PW, Hayden FG, Gao GF |title=A novel coronavirus outbreak of global health concern |journal=Lancet |volume=395 |issue=10223 |pages=470–473 |date=February 2020 |pmid=31986257 |pmc=7135038 |doi=10.1016/S0140-6736(20)30185-9 |title-link=doi |doi-access=free}}</ref><ref name="AutoDW-67">{{#invoke:cite journal|| vauthors=Cohen J | date=January 2020|title=Wuhan seafood market may not be source of novel virus spreading globally |url=https://www.science.org/content/article/wuhan-seafood-market-may-not-be-source-novel-virus-spreading-globally|journal=Science |doi=10.1126/science.abb0611 |doi-access=free |title-link=doi}}</ref> Official publications from the WHO reported the earliest onset of symptoms as 8{{spaces}}December 2019.<ref>{{#invoke:Cite web||date=12 January 2020|title=Novel Coronavirus – China|website=[[Organization:World Health Organization|World Health Organization]] (WHO) |url=https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/|url-status=dead|archive-date=14 January 2020|archive-url=https://web.archive.org/web/20200114185815/https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/}}</ref> Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020.<ref>{{#invoke:cite news|| vauthors=Kessler G |date=17 April 2020|title=Trump's false claim that the WHO said the coronavirus was 'not communicable' |newspaper={{wipe|The Washington Post}} |url=https://www.washingtonpost.com/politics/2020/04/17/trumps-false-claim-that-who-said-coronavirus-was-not-communicable/|url-status=live |access-date=17 April 2020|archive-date=17 April 2020|archive-url=https://archive.today/20200417193804/https://www.washingtonpost.com/politics/2020/04/17/trumps-false-claim-that-who-said-coronavirus-was-not-communicable/}}</ref><ref>{{#invoke:cite news ||vauthors=Kuo L |date=21 January 2020 |title=China confirms human-to-human transmission of coronavirus |work={{wipe|The Guardian}} |url=https://www.theguardian.com/world/2020/jan/20/coronavirus-spreads-to-beijing-as-china-confirms-new-cases|access-date=18 April 2020}}</ref> According to official Chinese sources, these were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals.<ref name="characteristicsZH">{{#invoke:cite journal ||title=[The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China] |language=zh |journal=Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi |volume=41 |issue=2 |pages=145–151 |date=February 2020 |pmid=32064853 |doi=10.3760/cma.j.issn.0254-6450.2020.02.003 |s2cid=211133882 |author1=Epidemiology Working Group For Ncip Epidemic Response |author2=Chinese Center for Disease Control Prevention}}</ref> In May 2020, George Gao, the director of the CDC, said animal samples collected from the seafood market had tested negative for the virus, indicating that the market was the site of an early [[Biology:Superspreader|superspreading event]], but that it was not the site of the initial outbreak.<ref>{{#invoke:cite news|| vauthors = Areddy JT |date=26 May 2020|title=China Rules Out Animal Market and Lab as Coronavirus Origin|work={{wipe|The Wall Street Journal}} |url=https://www.wsj.com/articles/china-rules-out-animal-market-and-lab-as-coronavirus-origin-11590517508|access-date=29 May 2020|url-access=subscription}}</ref> Traces of the virus have been found in wastewater samples that were collected in Milan and [[Place:Turin|Turin]], Italy, on 18 December 2019.<ref>{{#invoke:cite news|| vauthors=Kelland K |date=19 June 2020 |title=Italy sewage study suggests COVID-19 was there in December 2019|work=Reuters |url=https://www.reuters.com/article/us-health-coronavirus-italy-sewage/italy-sewage-study-suggests-covid-19-was-there-in-december-2019-idUSKBN23Q1J9|access-date=23 June 2020}}</ref>

By December 2019, the spread of infection was almost entirely driven by human-to-human transmission.<ref name="Epidemiology17Feb2020"/><ref>{{#invoke:cite journal ||vauthors=Heymann DL, Shindo N |title=COVID-19: what is next for public health? |journal=Lancet |volume=395 |issue=10224 |pages=542–545 |date=February 2020 |pmid=32061313 |pmc=7138015 |doi=10.1016/S0140-6736(20)30374-3 |title-link=doi |doi-access=free}}</ref> The number of COVID-19 cases in Hubei gradually increased, reaching sixty by 20 December,<ref>{{#invoke:Cite web|| date=14 March 2020 |vauthors=Bryner J |title=1st known case of coronavirus traced back to November in China |website=livescience.com |url=https://www.livescience.com/first-case-coronavirus-found.html|access-date=31 May 2020}}</ref> and at least 266 by 31 December.<ref>{{#invoke:cite news ||author=Canadian Politics |date=8 April 2020 |title=The birth of a pandemic: How COVID-19 went from Wuhan to Toronto |newspaper=National Post|url=https://nationalpost.com/news/politics/the-birth-of-a-pandemic-how-covid-19-went-from-wuhan-to-toronto |access-date=31 May 2020}}</ref> On 24 December, Wuhan Central Hospital sent a bronchoalveolar lavage fluid (BAL) sample from an unresolved clinical case to sequencing company Vision Medicals. On 27 and 28 December, Vision Medicals informed the Wuhan Central Hospital and the Chinese CDC of the results of the test, showing a new coronavirus.<ref>{{#invoke:cite news||author=高昱|date=26 February 2020|title=独家 {{!}} 新冠病毒基因测序溯源：警报是何时拉响的|language=zh|trans-title=Exclusive {{!}} Tracing the New Coronavirus gene sequencing: when did the alarm sound|work=Caixin|url=https://china.caixin.com/2020-02-26/101520972.html|access-date=1 March 2020|archive-url=https://web.archive.org/web/20200227094018/https://china.caixin.com/2020-02-26/101520972.html|archive-date=27 February 2020|url-status=dead}}</ref> A pneumonia cluster of unknown cause was observed on 26 December and treated by the doctor Zhang Jixian in Hubei Provincial Hospital, who informed the Wuhan Jianghan CDC on 27 December.<ref>{{#invoke:Cite web||author1=路子康 |title=最早上报疫情的她，怎样发现这种不一样的肺炎|website=中国网新闻 |location=北京|language=zh-cn |url=https://news.china.com/zw/news/13000776/20200209/37780703.html |archive-url=https://web.archive.org/web/20200302165302/https://news.china.com/zw/news/13000776/20200209/37780703.html|archive-date=2 March 2020|access-date=11 February 2020}}</ref> On 30 December, a test report addressed to Wuhan Central Hospital, from company CapitalBio Medlab, stated an erroneous positive result for [[Medicine:SARS|SARS]], causing a group of doctors at Wuhan Central Hospital to alert their colleagues and relevant hospital authorities of the result. The Wuhan Municipal Health Commission issued a notice to various medical institutions on "the treatment of pneumonia of unknown cause" that same evening.<ref>{{#invoke:Cite web||title=Undiagnosed pneumonia – China (HU): RFI|url=https://promedmail.org/promed-post/?id=6864153|access-date=7 May 2020|website=ProMED Mail |publisher=ProMED}}</ref> Eight of these doctors, including Li Wenliang (punished on 3{{spaces}}January),<ref>{{#invoke:cite news||date=7 February 2020|title='Hero who told the truth': Chinese rage over coronavirus death of whistleblower doctor|work={{wipe|The Guardian}}|url=https://www.theguardian.com/global-development/2020/feb/07/coronavirus-chinese-rage-death-whistleblower-doctor-li-wenliang}}</ref> were later admonished by the police for spreading false rumours and another, Ai Fen, was reprimanded by her superiors for raising the alarm.<ref>{{#invoke:cite news ||vauthors=Kuo L |date=11 March 2020 |title=Coronavirus: Wuhan doctor speaks out against authorities |work=The Guardian |location=London|url=https://www.theguardian.com/world/2020/mar/11/coronavirus-wuhan-doctor-ai-fen-speaks-out-against-authorities}}</ref>

The Wuhan Municipal Health Commission made the first public announcement of a pneumonia outbreak of unknown cause on 31 December, confirming 27 cases<ref name="AutoDW-69">{{#invoke:Cite web||title=Novel Coronavirus |url=https://www.who.int/westernpacific/emergencies/novel-coronavirus|access-date=6 February 2020|url-status=live|archive-url=https://web.archive.org/web/20200202151307/https://www.who.int/westernpacific/emergencies/novel-coronavirus|archive-date=2 February 2020|work=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref><ref>{{#invoke:cite news||date=31 December 2019|title=武汉现不明原因肺炎 官方确认属实：已经做好隔离|publisher=Xinhua Net 新華網 |url=https://news.163.com/19/1231/10/F1NGTJNJ00019K82.html|access-date=31 March 2020}}</ref><ref name="AutoDW-68">{{#invoke:Cite web||date=31 December 2019|script-title=zh:武汉市卫健委关于当前我市肺炎疫情的情况通报 |url=https://wjw.wuhan.gov.cn/front/web/showDetail/2019123108989|url-status=dead|archive-url=https://web.archive.org/web/20200109215413/https://wjw.wuhan.gov.cn/front/web/showDetail/2019123108989|archive-date=9 January 2020 |access-date=8 February 2020|work=WJW.Wuhan.gov.cn|publisher=Wuhan Municipal Health Commission|language=zh}}</ref>{{snd}}enough to trigger an investigation.<ref name="bbc50984025">{{#invoke:cite news||date=3 January 2020|title=Mystery pneumonia virus probed in China|work=BBC News|url=https://www.bbc.com/news/world-asia-china-50984025|url-status=live|access-date=29 January 2020|archive-url=https://web.archive.org/web/20200105051949/https://www.bbc.com/news/world-asia-china-50984025|archive-date=5 January 2020}}</ref>

During the early stages of the outbreak, the number of cases doubled approximately every seven and a half days.<ref name="Qun29Jan2020">{{#invoke:cite journal || vauthors = Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KS, Lau EH, Wong JY, Xing X, Xiang N, Wu Y, Li C, Chen Q, Li D, Liu T, Zhao J, Liu M, Tu W, Chen C, Jin L, Yang R, Wang Q, Zhou S, Wang R, Liu H, Luo Y, Liu Y, Shao G, Li H, Tao Z, Yang Y, Deng Z, Liu B, Ma Z, Zhang Y, Shi G, Lam TT, Wu JT, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z | display-authors = 6 | title = Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia | journal = The New England Journal of Medicine | volume = 382 | issue = 13 | pages = 1199–1207 | date = March 2020 | pmid = 31995857 | pmc = 7121484 | doi = 10.1056/NEJMoa2001316 | title-link = doi | doi-access = free }}</ref> In early and mid-January 2020, the virus spread to other Chinese provinces, helped by the Chinese New Year migration and Wuhan being a transport hub and major rail interchange.<ref name="WHOReport24Feb2020" /> On 20 January, China reported nearly 140 new cases in one day, including two people in Beijing and one in Shenzhen.<ref name="france2420200120">{{#invoke:cite news||date=20 January 2020|title=China confirms sharp rise in cases of SARS-like virus across the country|url=https://www.france24.com/en/20200120-china-confirms-sharp-rise-in-cases-of-sars-like-virus-across-the-country|url-status=live|access-date=20 January 2020|archive-url=https://web.archive.org/web/20200120055618/https://www.france24.com/en/20200120-china-confirms-sharp-rise-in-cases-of-sars-like-virus-across-the-country|archive-date=20 January 2020}}</ref> Later official data shows 6,174 people had already developed symptoms by then,<ref name="Epidemiology17Feb2020">{{#invoke:cite journal||vauthors=((The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team)) |date=February 2020|title=The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) – China, 2020 |journal=China CDC Weekly|volume=2|issue=8|pages=113–122|doi=10.46234/ccdcw2020.032 |pmid=34594836|pmc=839292|doi-access=free |title-link=doi}}</ref> and more may have been infected.<ref name="flattery">{{#invoke:cite news||date=25 April 2020|title=Flattery and foot dragging: China's influence over the WHO under scrutiny|work=The Globe and Mail |url=https://www.theglobeandmail.com/world/article-flattery-and-foot-dragging-chinas-influence-over-the-who-under/}}</ref> A report in ''The Lancet'' on 24 January indicated human transmission, strongly recommended personal protective equipment for health workers, and said testing for the virus was essential due to its "pandemic potential".<ref name="Huang24Jan2020">{{#invoke:cite journal ||vauthors=Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B |display-authors=6 |title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China |journal=Lancet |volume=395 |issue=10223 |pages=497–506 |date=February 2020 |pmid=31986264 |pmc=7159299 |doi=10.1016/S0140-6736(20)30183-5 |doi-access=free |title-link=doi}}</ref><ref name="Horton 18 March">{{#invoke:Cite web|| vauthors=Horton R |date=18 March 2020 |title=Scientists have been sounding the alarm on coronavirus for months. Why did Britain fail to act?|url=https://www.theguardian.com/commentisfree/2020/mar/18/coronavirus-uk-expert-advice-wrong |access-date=23 April 2020|website=The Guardian}}</ref> On 30 January, the WHO declared COVID-19 a [[Social:Public Health Emergency of International Concern|Public Health Emergency of International Concern]].<ref name="flattery" /> By this time, the outbreak spread by a factor of 100 to 200 times.<ref>{{#invoke:Cite web||date=2 June 2020|title=China delayed releasing coronavirus info, frustrating WHO |work=Associated Press |url=https://apnews.com/3c061794970661042b18d5aeaaed9fae|access-date=3 June 2020}}</ref>

Italy had its first confirmed cases on 31 January 2020, two tourists from China.<ref name="Corriere_20Jan">{{#invoke:Cite web||date=31 January 2020|title=Coronavirus: Primi due casi in Italia|trans-title=Coronavirus: First two cases in Italy|url=https://www.corriere.it/cronache/20_gennaio_30/coronavirus-italia-corona-9d6dc436-4343-11ea-bdc8-faf1f56f19b7.shtml|access-date=31 January 2020|work=Corriere della sera|language=it}}</ref> Italy overtook China as the country with the most deaths on 19 March 2020.<ref name="sky11960412">{{#invoke:Cite web||title=Coronavirus: Number of COVID-19 deaths in Italy surpasses China as total reaches 3,405|url=https://news.sky.com/story/coronavirus-number-of-covid-19-deaths-in-italy-surpasses-china-as-total-reaches-3-405-11960412|access-date=7 May 2020|publisher=Sky News}}</ref> By 26 March the United States had overtaken China and Italy with the highest number of confirmed cases in the world.<ref name="NYT-20200326">{{#invoke:cite news|| vauthors = McNeil Jr DG |date=26 March 2020|title=The U.S. Now Leads the World in Confirmed Coronavirus Cases|work={{wipe|The New York Times}}|url=https://www.nytimes.com/2020/03/26/health/usa-coronavirus-cases.html |archive-url=https://web.archive.org/web/20200326211527/https://www.nytimes.com/2020/03/26/health/usa-coronavirus-cases.html |archive-date=26 March 2020 |url-access=subscription |url-status=live|access-date=27 March 2020}}</ref> Research on coronavirus genomes indicates the majority of COVID-19 cases in New York came from European travellers, rather than directly from China or any other Asian country.<ref name="20200408nytimes">{{#invoke:cite news||date=8 April 2020|title=Studies Show N.Y. Outbreak Originated in Europe|work={{wipe|The New York Times}}|url=https://www.nytimes.com/2020/04/08/us/coronavirus-live-updates.html |archive-url=https://web.archive.org/web/20200408185016/https://www.nytimes.com/2020/04/08/us/coronavirus-live-updates.html |archive-date=8 April 2020 |url-access=subscription |url-status=live}}</ref> Retesting of prior samples found a person in France who had the virus on 27 December 2019,<ref name="France-retest">{{#invoke:cite news|| vauthors = Irish J |date=4 May 2020|title=After retesting samples, French hospital discovers COVID-19 case from December|work={{wipe|Reuters}}| veditors = Lough RM, Graff P |url=https://www.reuters.com/article/us-health-coronavirus-france-idUSKBN22G20L|access-date=4 May 2020}}</ref><ref name="Deslandes-2020">{{#invoke:cite journal || vauthors = Deslandes A, Berti V, Tandjaoui-Lambotte Y, Alloui C, Carbonnelle E, Zahar JR, Brichler S, Cohen Y | display-authors = 6 | title = SARS-CoV-2 was already spreading in France in late December 2019 | journal = International Journal of Antimicrobial Agents | volume = 55 | issue = 6 | pages = 106006 | date = June 2020 | pmid = 32371096 | pmc = 7196402 | doi = 10.1016/j.ijantimicag.2020.106006 }}</ref> and a person in the United States who died from the disease on 6{{spaces}}February 2020.<ref name="PBS-2wks">{{#invoke:Cite web||date=22 April 2020|title=2 died with coronavirus weeks before 1st U.S. virus death|url=https://www.pbs.org/newshour/nation/2-died-with-coronavirus-weeks-before-1st-u-s-virus-death|access-date=23 April 2020|website=PBS NewsHour}}</ref>

RT-PCR testing of untreated wastewater samples from Brazil and Italy have suggested detection of SARS-CoV-2 as early as November and December 2019, respectively, but the methods of such sewage studies have not been optimised, many have not been peer-reviewed, details are often missing, and there is a risk of false positives due to contamination or if only one gene target is detected.<ref>{{#invoke:cite journal || vauthors = Michael-Kordatou I, Karaolia P, Fatta-Kassinos D | title = Sewage analysis as a tool for the COVID-19 pandemic response and management: the urgent need for optimised protocols for SARS-CoV-2 detection and quantification | journal = Journal of Environmental Chemical Engineering | volume = 8 | issue = 5 | pages = 104306 | date = October 2020 | pmid = 32834990 | pmc = 7384408 | doi = 10.1016/j.jece.2020.104306 }}</ref> A September 2020 review journal article said, "The possibility that the COVID‑19 infection had already spread to Europe at the end of last year is now indicated by abundant, even if partially circumstantial, evidence", including pneumonia case numbers and radiology in France and Italy in November and December.<ref name=platto>{{#invoke:cite journal || vauthors = Platto S, Xue T, Carafoli E | title = COVID19: an announced pandemic | journal = Cell Death & Disease | volume = 11 | issue = 9 | pages = 799 | date = September 2020 | pmid = 32973152 | pmc = 7513903 | doi = 10.1038/s41419-020-02995-9 }}</ref>

{{As of|2021|10|1}}, ''{{wipe|Reuters}}'' reported that it had estimated the worldwide total number of deaths due to COVID‑19 to have exceeded five million.<ref>{{#invoke:cite news||url=https://www.reuters.com/world/global-covid-19-deaths-hit-5-million-delta-variant-sweeps-world-2021-10-02/|title=Global COVID-19 deaths hit 5 million as Delta variant sweeps the world| vauthors = Kavya B, Abraham R |agency=Reuters| veditors = Shumaker L, Wardell J |date=3 October 2021|work=Reuters.com}}</ref>

The Public Health Emergency of International Concern for COVID-19 ended on May 5, 2023. By this time, everyday life in most countries had returned to how it was before the pandemic.<ref>{{#invoke:cite web||title=From emergency response to long-term COVID-19 disease management: sustaining gains made during the COVID-19 pandemic|url=https://www.who.int/publications/i/item/WHO-WHE-SPP-2023.1|website=www.who.int|publisher=World Health Organization|access-date=9 May 2023|language=en}}</ref><ref>{{#invoke:cite web||date=5 May 2023|title=WHO ends global health emergency declaration for COVID-19|url=https://www.npr.org/sections/goatsandsoda/2023/05/05/1174269442/who-ends-global-health-emergency-declaration-for-covid-19|website=NPR|first1=Giulia|last1=Heyward|first2=Marc|last2=Silver|access-date=9 May 2023}}</ref>

== Misinformation ==
{{Main|Social:COVID-19 misinformation}}

After the initial outbreak of COVID{{nbhyph}}19, misinformation and [[Social:Disinformation|disinformation]] regarding the origin, scale, prevention, treatment, and other aspects of the disease rapidly spread online.<ref name="bbc_misinfo">{{#invoke:cite news ||url=https://www.bbc.com/news/blogs-trending-51271037 |title=China coronavirus: Misinformation spreads online about origin and scale |date=30 January 2020 |work=BBC News |access-date=10 February 2020 |archive-url=https://web.archive.org/web/20200204163412/https://www.bbc.com/news/blogs-trending-51271037 |archive-date=4 February 2020 |url-status=live}}</ref><ref name="GUAR">{{#invoke:cite news ||url=https://www.theguardian.com/world/2020/jan/31/bat-soup-dodgy-cures-and-diseasology-the-spread-of-coronavirus-bunkum |title=Bat soup, dodgy cures and 'diseasology': the spread of coronavirus misinformation |date=31 January 2020 |access-date=3 February 2020 | vauthors = Taylor J |newspaper={{wipe|The Guardian}} |archive-url=https://web.archive.org/web/20200202141231/https://www.theguardian.com/world/2020/jan/31/bat-soup-dodgy-cures-and-diseasology-the-spread-of-coronavirus-bunkum |archive-date=2 February 2020 |url-status=live}}</ref><ref name="RunningList">{{#invoke:Cite web||url=https://www.buzzfeednews.com/article/janelytvynenko/coronavirus-disinformation-spread |title=Here's A Running List Of Disinformation Spreading About The Coronavirus |website=Buzzfeed News |access-date=8 February 2020 |archive-url=https://web.archive.org/web/20200206212717/https://www.buzzfeednews.com/article/janelytvynenko/coronavirus-disinformation-spread |archive-date=6 February 2020 |url-status=dead}}</ref>

In September 2020, the US Centers for Disease Control and Prevention (CDC) published preliminary estimates of the risk of death by age groups in the United States, but those estimates were widely misreported and misunderstood.<ref>{{#invoke:Cite web||date=11 February 2020|title=Coronavirus Disease 2019 (COVID-19)|url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html|access-date=10 October 2020|website=U.S. Centers for Disease Control and Prevention (CDC)}}</ref><ref>{{#invoke:Cite web||date=8 October 2020|title=Misleading claim circulates online about infection fatality ratio of Covid-19 in the US|url=https://factcheck.afp.com/misleading-claim-circulates-online-about-infection-fatality-ratio-covid-19-us|access-date=10 October 2020|website=Fact Check}}</ref>

== Other species ==

Humans appear to be capable of spreading the virus to some other animals,<ref name="Gryseels_2021_MammalReview">{{#invoke:cite journal||display-authors=3 |last1=Gryseels |first1=Sophie |last2=De Bruyn |first2=Luc |last3=Gyselings |first3=Ralf |last4=Calvignac-Spencer |first4=Sébastien |last5=Leendertz |first5=Fabian H. |last6=Leirs |first6=Herwig |title=Risk of human-to-wildlife transmission of SARS-CoV-2 |journal=Mammal Review |date=April 2021 |volume=51 |issue=2 |pages=272–292 |doi=10.1111/mam.12225 |pmid=33230363 |pmc=7675675 |hdl=10067/1726730151162165141 |language=en |issn=0305-1838}}</ref><ref name="TanLam2022_NatComm">{{#invoke:cite journal||display-authors=3 |last1=Tan |first1=Cedric C. S. |last2=Lam |first2=Su Datt |last3=Richard |first3=Damien |last4=Owen |first4=Christopher J. |last5=Berchtold |first5=Dorothea |last6=Orengo |first6=Christine |last7=Nair |first7=Meera Surendran |last8=Kuchipudi |first8=Suresh V. |last9=Kapur |first9=Vivek |last10=van Dorp |first10=Lucy |last11=Balloux |first11=François |title=Transmission of SARS-CoV-2 from humans to animals and potential host adaptation |journal=Nature Communications |date=27 May 2022 |volume=13 |issue=1 |pages=2988 |doi=10.1038/s41467-022-30698-6 |pmid=35624123 |pmc=9142586 |bibcode=2022NatCo..13.2988T |url=https://doi.org/10.1038/s41467-022-30698-6 |access-date=28 February 2023 |language=en |issn=2041-1723}}</ref> a type of disease transmission referred to as [[Biology:Anthroponotic disease|zooanthroponosis]].<ref name="Pappas_MDPI_2022">{{#invoke:cite journal ||last1=Pappas |first1=Georgios |last2=Vokou |first2=Despoina |last3=Sainis |first3=Ioannis |last4=Halley |first4=John M. |title=SARS-CoV-2 as a Zooanthroponotic Infection: Spillbacks, Secondary Spillovers, and Their Importance |journal=Microorganisms |date=November 2022 |volume=10 |issue=11 |pages=2166 |doi=10.3390/microorganisms10112166 |pmid=36363758 |pmc=9696655 |language=en |issn=2076-2607|doi-access=free }}</ref><ref name="MunirAshraf_2020">{{#invoke:cite journal ||display-authors=3|last1=Munir |first1=Khalid |last2=Ashraf |first2=Shoaib |last3=Munir |first3=Isra |last4=Khalid |first4=Hamna |last5=Muneer |first5=Mohammad Akram |last6=Mukhtar |first6=Noreen |last7=Amin |first7=Shahid |last8=Ashraf |first8=Sohaib |last9=Imran |first9=Muhammad Ahmad |last10=Chaudhry |first10=Umer |last11=Zaheer |first11=Muhammad Usman |last12=Arshad |first12=Maria |last13=Munir |first13=Rukhsana |last14=Ahmad |first14=Ali |last15=Zhao |first15=Xin |title=Zoonotic and reverse zoonotic events of SARS-CoV-2 and their impact on global health |journal=Emerging Microbes & Infections |date=1 January 2020 |volume=9 |issue=1 |pages=2222–2235 |doi=10.1080/22221751.2020.1827984 |pmid=32967592 |pmc=7594747 }}</ref>

Some pets, especially cats and [[Biology:Ferret|ferret]]s, can catch this virus from infected humans.<ref name="Kampf-2020">{{#invoke:cite journal || vauthors = Kampf G, Brüggemann Y, Kaba HE, Steinmann J, Pfaender S, Scheithauer S, Steinmann E | display-authors = 6 | title = Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2 | journal = The Journal of Hospital Infection | volume = 106 | issue = 4 | pages = 678–697 | date = December 2020 | pmid = 32956786 | pmc = 7500278 | doi = 10.1016/j.jhin.2020.09.022 }}</ref><ref>{{#invoke:cite journal || vauthors = Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, Liu R, He X, Shuai L, Sun Z, Zhao Y, Liu P, Liang L, Cui P, Wang J, Zhang X, Guan Y, Tan W, Wu G, Chen H, Bu Z | display-authors = 6 | title = Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2 | journal = Science | volume = 368 | issue = 6494 | pages = 1016–1020 | date = May 2020 | pmid = 32269068 | pmc = 7164390 | doi = 10.1126/science.abb7015 }}</ref> Symptoms in cats include respiratory (such as a cough) and digestive symptoms.<ref name="Kampf-2020" /> Cats can spread the virus to other cats, and may be able to spread the virus to humans, but cat-to-human transmission of SARS-CoV-2 has not been proven.<ref name="Kampf-2020" /><ref name="Tazerji-2020">{{#invoke:cite journal || vauthors = Salajegheh Tazerji S, Magalhães Duarte P, Rahimi P, Shahabinejad F, Dhakal S, Singh Malik Y, Shehata AA, Lama J, Klein J, Safdar M, Rahman MT, Filipiak KJ, Rodríguez-Morales AJ, Sobur MA, Kabir F, Vazir B, Mboera L, Caporale M, Islam MS, Amuasi JH, Gharieb R, Roncada P, Musaad S, Tilocca B, Koohi MK, Taghipour A, Sait A, Subbaram K, Jahandideh A, Mortazavi P, Abedini MA, Hokey DA, Hogan U, Shaheen MN, Elaswad A, Elhaig MM, Fawzy M | display-authors = 3 | title = Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: an updated review | journal = Journal of Translational Medicine | volume = 18 | issue = 1 | pages = 358 | date = September 2020 | pmid = 32957995 | pmc = 7503431 | doi = 10.1186/s12967-020-02534-2 |doi-access=free}}</ref> Compared to cats, dogs are less susceptible to this infection.<ref name="Tazerji-2020" /> Behaviours which increase the risk of transmission include kissing, licking, and petting the animal.<ref name="Tazerji-2020" />

The virus does not appear to be able to infect pigs, ducks, or chickens at all.<ref name="Kampf-2020" /> [[Biology:Mouse|Mice]], rats, and rabbits, if they can be infected at all, are unlikely to be involved in spreading the virus.<ref name="Tazerji-2020" />

Tigers and lions in zoos have become infected as a result of contact with infected humans.<ref name="Tazerji-2020" /> As expected, monkeys and great ape species such as [[Biology:Orangutan|orangutan]]s can also be infected with the COVID‑19 virus.<ref name="Tazerji-2020" />

[[Biology:Mink|Mink]]s, which are in the same family as ferrets, have been infected.<ref name="Tazerji-2020" /> Minks may be asymptomatic, and can also spread the virus to humans.<ref name="Tazerji-2020" /> Multiple countries have identified infected animals in mink farms.<ref name="Gorman-2021">{{#invoke:cite news|| vauthors = Gorman J |date=22 January 2021|title=The Coronavirus Kills Mink, So They Too May Get a Vaccine|work=The New York Times |url=https://www.nytimes.com/2021/01/22/science/covid-mink-vaccine.html |archive-url=https://ghostarchive.org/archive/20211228/https://www.nytimes.com/2021/01/22/science/covid-mink-vaccine.html |archive-date=28 December 2021 |url-access=limited|access-date=24 February 2021|issn=0362-4331| url-status=live}}</ref> {{wipe|Denmark}}, a major producer of mink pelts, ordered the slaughter of all minks over fears of viral mutations,<ref name="Gorman-2021" /> following an outbreak referred to as Cluster 5. A vaccine for mink and other animals is being researched.<ref name="Gorman-2021" />

== Research ==
{{Further|Biology:COVID-19 drug development}}

International research on vaccines and medicines in COVID{{nbhyph}}19 is underway by government organisations, academic groups, and industry researchers.<ref name="dhama">{{#invoke:cite journal || vauthors = Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP, Chaicumpa W | display-authors = 6 | title = COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics | journal = Human Vaccines & Immunotherapeutics | volume = 16 | issue = 6 | pages = 1232–1238 | date = June 2020 | pmid = 32186952 | pmc = 7103671 | doi = 10.1080/21645515.2020.1735227 | title-link = doi | doi-access = free }}</ref><ref name="zhang2020">{{#invoke:cite journal || vauthors = Zhang L, Liu Y | title = Potential interventions for novel coronavirus in China: A systematic review | journal = Journal of Medical Virology | volume = 92 | issue = 5 | pages = 479–490 | date = May 2020 | pmid = 32052466 | pmc = 7166986 | doi = 10.1002/jmv.25707 }}</ref> The CDC has classified it to require a BSL3 grade laboratory.<ref name=inlbg>{{#invoke:Cite web||title=Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19) |url=https://www.cdc.gov/coronavirus/2019-ncov/lab/lab-biosafety-guidelines.html |website=Coronavirus Disease 2019 (COVID-19) Lab Biosafety Guidelines |date=11 February 2020 |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=1 April 2020}}</ref> There has been a great deal of COVID‑19 research, involving accelerated research processes and publishing shortcuts to meet the global demand.<ref name="Aristovnik et al. 2020">{{#invoke:cite journal||vauthors=Aristovnik A, Ravšelj D, Umek L|date=November 2020|title=A Bibliometric Analysis of COVID-19 across Science and Social Science Research Landscape|journal=Sustainability|volume=12|issue=21|pages=9132|doi=10.3390/su12219132|doi-access=free | title-link = doi }}</ref>

{{As of|2020|December}}, hundreds of [[Engineering:Clinical trial|clinical trial]]s have been undertaken, with research happening on every continent except Antarctica.<ref>{{#invoke:cite journal || vauthors = Kupferschmidt K |title=First-of-its-kind African trial tests common drugs to prevent severe COVID-19 |journal=Science |date=3 December 2020 |doi=10.1126/science.abf9987 |doi-access=free | title-link=doi |url=https://www.science.org/content/article/first-its-kind-african-trial-tests-common-drugs-prevent-severe-covid-19 |access-date=8 March 2022 }}</ref> {{As of|2020|November}}, more than 200 possible treatments have been studied in humans.<ref>{{#invoke:Cite magazine || vauthors = Reardon S |date= November 2020|title=For COVID Drugs, Months of Frantic Development Lead to Few Outright Successes|url=https://www.scientificamerican.com/article/for-covid-drugs-months-of-frantic-development-lead-to-few-outright-successes/|access-date=10 December 2020|magazine=Scientific American }}</ref>

=== Transmission and prevention research ===
{{Further|Medicine:COVID-19 vaccine}}

[[Modeling and simulation|Modelling]] research has been conducted with several objectives, including predictions of the dynamics of transmission,<ref>{{#invoke:cite journal || vauthors = Kucharski AJ, Russell TW, Diamond C, Liu Y, Edmunds J, Funk S, Eggo RM | display-authors = 6 | title = Early dynamics of transmission and control of COVID-19: a mathematical modelling study | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 5 | pages = 553–558 | date = May 2020 | pmid = 32171059 | pmc = 7158569 | doi = 10.1016/S1473-3099(20)30144-4 | doi-access = free | title-link = doi }}</ref> diagnosis and prognosis of infection,<ref>{{#invoke:cite journal||date=3 February 2021|title=Update to living systematic review on prediction models for diagnosis and prognosis of covid-19|url=https://pubmed.ncbi.nlm.nih.gov/33536183|journal=BMJ (Clinical Research Ed.)|volume=372|pages=n236|doi=10.1136/bmj.n236|issn=1756-1833|pmid=33536183|s2cid=231775762}}</ref> estimation of the impact of interventions,<ref>{{#invoke:cite journal || vauthors = Giordano G, Blanchini F, Bruno R, Colaneri P, Di Filippo A, Di Matteo A, Colaneri M | display-authors = 6 | title = Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy | journal = Nature Medicine | volume = 26 | issue = 6 | pages = 855–860 | date = June 2020 | pmid = 32322102 | pmc = 7175834 | doi = 10.1038/s41591-020-0883-7|arxiv=2003.09861 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Prem K, Liu Y, Russell TW, Kucharski AJ, Eggo RM, Davies N, Jit M, Klepac P | display-authors = 6 | title = The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study | journal = The Lancet. Public Health | volume = 5 | issue = 5 | pages = e261–e270 | date = May 2020 | pmid = 32220655 | pmc = 7158905 | doi = 10.1016/S2468-2667(20)30073-6 | doi-access = free | title-link = doi }}</ref> or allocation of resources.<ref>{{#invoke:cite journal || vauthors = Emanuel EJ, Persad G, Upshur R, Thome B, Parker M, Glickman A, Zhang C, Boyle C, Smith M, Phillips JP | display-authors = 6 | title = Fair Allocation of Scarce Medical Resources in the Time of Covid-19 | journal = The New England Journal of Medicine | volume = 382 | issue = 21 | pages = 2049–2055 | date = May 2020 | pmid = 32202722 | doi = 10.1056/NEJMsb2005114 | doi-access = free | title-link = doi }}</ref> Modelling studies are mostly based on [[Compartmental models in epidemiology|compartmental models in epidemiology]],<ref>{{#invoke:cite journal ||doi=10.1098/rspa.1927.0118 |volume=115 |issue=772 |pages=700–721 |title=A contribution to the mathematical theory of epidemics |journal=Proceedings of the Royal Society of London. Series A, Containing Papers of a Mathematical and Physical Character |year=1927 |bibcode=1927RSPSA.115..700K |doi-access=free | title-link = doi | vauthors = Kermack WO, McKendrick AG }}</ref> estimating the number of infected people over time under given conditions. Several other types of models have been developed and used during the COVID{{nbhyph}}19 pandemic including [[Computational fluid dynamics|computational fluid dynamics]] models to study the flow physics of COVID{{nbhyph}}19,<ref>{{#invoke:cite journal ||doi=10.1017/jfm.2020.330 |volume=894 |pages=–2 | vauthors = Mittal R, Ni R, Seo JH |title=The flow physics of COVID-19 |journal=Journal of Fluid Mechanics |year=2020 |arxiv=2004.09354 |bibcode=2020JFM...894F...2M |doi-access=free | title-link = doi }}</ref> retrofits of crowd movement models to study occupant exposure,<ref>{{#invoke:cite journal || vauthors = Ronchi E, Lovreglio R | title = EXPOSED: An occupant exposure model for confined spaces to retrofit crowd models during a pandemic | journal = Safety Science | volume = 130 | pages = 104834 | date = October 2020 | pmid = 32834509 | pmc = 7373681 | doi = 10.1016/j.ssci.2020.104834 | arxiv = 2005.04007 | doi-access = free | title-link = doi }}</ref> mobility-data based models to investigate transmission,<ref>{{#invoke:cite journal || vauthors = Badr HS, Du H, Marshall M, Dong E, Squire MM, Gardner LM | title = Association between mobility patterns and COVID-19 transmission in the USA: a mathematical modelling study | journal = The Lancet Infectious Diseases | volume = 20 | issue = 11 | pages = 1247–1254 | date = November 2020 | pmid = 32621869 | pmc = 7329287 | doi = 10.1016/S1473-3099(20)30553-3 | doi-access = free | title-link = doi }}</ref> or the use of macroeconomic models to assess the economic impact of the pandemic.<ref>{{#invoke:cite journal || vauthors = McKibbin W, Roshen F | title = The global macroeconomic impacts of COVID-19: Seven scenarios |journal=CAMA Working Paper |year=2020 |doi=10.2139/ssrn.3547729 |s2cid=216307705 |url= https://cama.crawford.anu.edu.au/sites/default/files/publication/cama_crawford_anu_edu_au/2020-03/19_2020_mckibbin_fernando_0.pdf }}</ref>

=== Treatment-related research ===
[[File:Fmolb-07-585899-g001.jpg|thumb|Seven possible drug targets in viral replication process and drugs]]

Repurposed [[Biology:Antiviral drug|antiviral drug]]s make up most of the research into COVID‑19 treatments.<ref name="milken">{{#invoke:Cite web||date=21 April 2020|title=COVID-19 treatment and vaccine tracker|url=https://milkeninstitute.org/sites/default/files/2020-04/Covid19%20Tracker%20NEW4-21-20-2.pdf|access-date=21 April 2020|publisher=Milken Institute }}</ref><ref name="koch">{{#invoke:Cite web|| vauthors = Koch S, Pong W |date=13 March 2020|title=First up for COVID-19: nearly 30 clinical readouts before end of April|url=https://www.biocentury.com/article/304658|access-date=1 April 2020|publisher=BioCentury Inc.}}</ref> Other candidates in trials include vasodilators, [[Biology:Corticosteroid|corticosteroid]]s, immune therapies, [[Chemistry:Lipoic acid|lipoic acid]], [[Chemistry:Bevacizumab|bevacizumab]], and [[Biology:Recombinant DNA|recombinant]] angiotensin-converting enzyme 2.<ref name="koch" />

In March 2020, the [[Organization:World Health Organization|World Health Organization]] (WHO) initiated the [[Medicine:Solidarity trial|Solidarity trial]] to assess the treatment effects of some promising drugs: an [[Chemistry:Experimental drug|experimental drug]] called remdesivir; [[Chemistry:Antimalarial medication|anti-malarial]] drugs chloroquine and hydroxychloroquine; two anti-HIV drugs, lopinavir/ritonavir; and interferon-beta.<ref name="kai">{{#invoke:cite journal|| vauthors = Kupferschmidt K, Cohen J |date=March 2020|title=WHO launches global megatrial of the four most promising coronavirus treatments|journal=Science|doi=10.1126/science.abb8497|doi-access = free | title-link = doi }}</ref><ref>{{#invoke:Cite web||url=https://news.un.org/en/story/2020/03/1059722|title=UN health chief announces global 'solidarity trial' to jumpstart search for COVID-19 treatment|date=18 March 2020|website=UN News|access-date=23 March 2020|archive-url=https://web.archive.org/web/20200323101633/https://news.un.org/en/story/2020/03/1059722|archive-date=23 March 2020|url-status=live}}</ref> More than 300 active clinical trials are underway as of April 2020.<ref name="Sanders202022" />

Research on the antimalarial drugs [[Chemistry:Hydroxychloroquine|hydroxychloroquine]] and [[Chemistry:Chloroquine|chloroquine]] showed that they were ineffective at best,<ref name="20200526nytimes">{{#invoke:Cite web||date=26 May 2020|title=Citing safety concerns, the W.H.O. paused tests of a drug Trump said he had taken|url=https://www.nytimes.com/2020/05/26/world/coronavirus-news.html |archive-url=https://web.archive.org/web/20200526041004/https://www.nytimes.com/2020/05/26/world/coronavirus-news.html |archive-date=26 May 2020 |url-access=subscription |url-status=live|work={{wipe|The New York Times}}}}</ref><ref>{{citation-attribution|1={{#invoke:cite press release||title=Hydroxychloroquine does not benefit adults hospitalized with COVID-19|website=National Institutes of Health (NIH)|date=9 November 2020|url=https://www.nih.gov/news-events/news-releases/hydroxychloroquine-does-not-benefit-adults-hospitalized-covid-19|access-date=9 November 2020}} }}</ref> and that they may reduce the antiviral activity of remdesivir.<ref>{{citation-attribution|1={{#invoke:cite press release||title=Coronavirus (COVID-19) Update: FDA Warns of Newly Discovered Potential Drug Interaction That May Reduce Effectiveness of a COVID-19 Treatment Authorized for Emergency Use|website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|date=15 June 2020|url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-warns-newly-discovered-potential-drug-interaction-may-reduce|access-date=15 June 2020}} }}</ref> {{As of|2020|May|alt=By May 2020}}, France, Italy, and Belgium had banned the use of hydroxychloroquine as a COVID‑19 treatment.<ref>{{#invoke:Cite web||date=27 May 2020|title=France bans use of hydroxychloroquine, drug touted by Trump, in coronavirus patients|url=https://www.cbsnews.com/news/france-bans-use-of-hydroxychloroquine-drug-touted-by-trump-to-treat-coronavirus/|publisher=CBS News}}</ref>

In June, initial results from the randomised [[Medicine:RECOVERY Trial|RECOVERY Trial]] in the United Kingdom showed that dexamethasone reduced mortality by one third for people who are critically ill on ventilators and one fifth for those receiving supplemental oxygen.<ref>{{#invoke:cite news || vauthors = Boseley S |title=Recovery trial for Covid-19 treatments: what we know so far |url= https://www.theguardian.com/world/2020/jun/16/recovery-trial-for-covid-19-treatments-what-we-know-so-far |access-date=21 June 2020 |work={{wipe|The Guardian}} |date=16 June 202}}</ref> Because this is a well-tested and widely available treatment, it was welcomed by the WHO, which is in the process of updating treatment guidelines to include dexamethasone and other steroids.<ref>{{#invoke:cite press release ||title=WHO welcomes preliminary results about dexamethasone use in treating critically ill COVID-19 patients |url=https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients |website=[[Organization:World Health Organization|World Health Organization]] (WHO) |access-date=21 June 2020 |date=16 June 2020}}</ref><ref>{{#invoke:Cite press release||title=Q&A: Dexamethasone and COVID-19|url=https://www.who.int/news-room/q-a-detail/q-a-dexamethasone-and-covid-19|access-date=12 July 2020|website=[[Organization:World Health Organization|World Health Organization]] (WHO)}}</ref> Based on those preliminary results, dexamethasone treatment has been recommended by the NIH for patients with COVID‑19 who are mechanically ventilated or who require supplemental oxygen but not in patients with COVID‑19 who do not require supplemental oxygen.<ref>{{#invoke:Cite web||title=Corticosteroids|url=https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/|access-date=12 July 2020|website=COVID-19 Treatment Guidelines|publisher=National Institutes of Health}}</ref>

In September 2020, the WHO released updated guidance on using corticosteroids for COVID‑19.<ref name="WHO guidance">{{#invoke:cite report || vauthors=((World Health Organization)) | year=2020 | title=Corticosteroids for COVID-19: living guidance, 2 September 2020 |  id=WHO/2019-nCoV/Corticosteroids/2020.1 | hdl=10665/334125 | hdl-access=free }}</ref><ref>{{#invoke:Cite web|| title=WHO updates clinical care guidance with corticosteroid recommendations | publisher=[[Organization:World Health Organization|World Health Organization]] (WHO) | url=https://www.who.int/news-room/feature-stories/detail/who-updates-clinical-care-guidance-with-corticosteroid-recommendations | access-date=25 January 2022}}</ref> The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID‑19 (strong recommendation, based on moderate certainty evidence).<ref name="WHO guidance" /> The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID‑19 (conditional recommendation, based on low certainty evidence).<ref name="WHO guidance" /> The updated guidance was based on a meta-analysis of clinical trials of critically ill COVID‑19 patients.<ref>{{#invoke:cite journal || vauthors = Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LC, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JP, Horby P, Jüni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Møller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC | display-authors = 6 | title = Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis | journal = JAMA | volume = 324 | issue = 13 | pages = 1330–1341 | date = October 2020 | pmid = 32876694 | pmc = 7489434 | doi = 10.1001/jama.2020.17023 | collaboration = The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group | s2cid = 221467783 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Prescott HC, Rice TW | title = Corticosteroids in COVID-19 ARDS: Evidence and Hope During the Pandemic | journal = JAMA | volume = 324 | issue = 13 | pages = 1292–1295 | date = October 2020 | pmid = 32876693 | doi = 10.1001/jama.2020.16747 | s2cid = 221468015 | doi-access = free | title-link = doi }}</ref>

In September 2020, the [[Organization:European Medicines Agency|European Medicines Agency]] (EMA) endorsed the use of dexamethasone in adults and adolescents from twelve years of age and weighing at least {{convert|40|kg}} who require supplemental oxygen therapy.<ref name="EMA PR">{{#invoke:cite press release || title=EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation | website=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | date=18 September 2020 | url=https://www.ema.europa.eu/en/news/ema-endorses-use-dexamethasone-covid-19-patients-oxygen-mechanical-ventilation | access-date=21 September 2020}} Text was copied from this source which is European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{#invoke:cite report ||url=https://www.ema.europa.eu/en/documents/other/dexamethasone-covid19-article-53-procedure-assessment-report_en.pdf |title=Dexamethasone in hospitalised patients with COVID-19 |publisher=European Medicines Agency |date=17 September 2020}}</ref> Dexamethasone can be taken [[Medicine:Oral administration|by mouth]] or given as an injection or infusion (drip) into a vein.<ref name="EMA PR" />

In November 2020, the US [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) issued an emergency use authorisation for the investigational monoclonal antibody therapy [[Chemistry:Bamlanivimab|bamlanivimab]] for the treatment of mild-to-moderate COVID‑19.<ref name="FDA bamlanivimab EUA">{{citation-attribution|1={{#invoke:cite press release || title=Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibody for Treatment of COVID-19 | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | date=9 November 2020 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibody-treatment-covid-19 | access-date=9 November 2020}} }}</ref> Bamlanivimab is authorised for people with positive results of direct SARS-CoV-2 viral testing who are twelve years of age and older weighing at least {{convert|40|kg}}, and who are at high risk for progressing to severe COVID‑19 or hospitalisation.<ref name="FDA bamlanivimab EUA" /> This includes those who are 65 years of age or older, or who have chronic medical conditions.<ref name="FDA bamlanivimab EUA" />

In February 2021, the FDA issued an emergency use authorisation (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID‑19 in people twelve years of age or older weighing at least {{convert|40|kg|lb}} who test positive for SARS‑CoV‑2 and who are at high risk for progressing to severe COVID‑19. The authorised use includes treatment for those who are 65 years of age or older or who have certain chronic medical conditions.<ref name="FDA PR 20210209">{{citation-attribution|1={{#invoke:cite press release||title=FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19|website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|date=10 February 2021|url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19-0|access-date=9 February 2021}} }}</ref>

In April 2021, the FDA revoked the emergency use authorisation (EUA) that allowed for the investigational monoclonal antibody therapy bamlanivimab, when administered alone, to be used for the treatment of mild-to-moderate COVID‑19 in adults and certain paediatric patients.<ref name="FDA PR 20210416">{{citation-attribution|1={{#invoke:cite press release || title=Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | date=16 April 2021 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-monoclonal-antibody-bamlanivimab | access-date=16 April 2021}} }}</ref>

==== Cytokine storm ====
[[File:Fimmu-11-01648-g003.jpg|thumb|Various therapeutic strategies for targeting cytokine storm|right]]

A [[Medicine:Cytokine storm|cytokine storm]] can be a complication in the later stages of severe COVID‑19. A cytokine storm is a potentially deadly immune reaction where a large amount of pro-inflammatory cytokines and [[Biology:Chemokine|chemokine]]s are released too quickly. A cytokine storm can lead to ARDS and multiple organ failure.<ref>{{#invoke:cite journal || vauthors = Li X, Geng M, Peng Y, Meng L, Lu S | title = Molecular immune pathogenesis and diagnosis of COVID-19 | journal = Journal of Pharmaceutical Analysis | volume = 10 | issue = 2 | pages = 102–108 | date = April 2020 | pmid = 32282863 | pmc = 7104082 | doi = 10.1016/j.jpha.2020.03.001 }}</ref> Data collected from Jin Yin-tan Hospital in Wuhan, China indicates that patients who had more severe responses to COVID‑19 had greater amounts of pro-inflammatory cytokines and chemokines in their system than patients who had milder responses. These high levels of pro-inflammatory cytokines and chemokines indicate presence of a cytokine storm.<ref>{{#invoke:cite journal || vauthors = Zhao Z, Wei Y, Tao C | title = An enlightening role for cytokine storm in coronavirus infection | journal = Clinical Immunology | volume = 222 | pages = 108615 | date = January 2021 | pmid = 33203513 | pmc = 7583583 | doi = 10.1016/j.clim.2020.108615 }}</ref>

[[Chemistry:Tocilizumab|Tocilizumab]] has been included in treatment guidelines by China's National Health Commission after a small study was completed.<ref name="tocil-1">{{#invoke:cite news ||vauthors = Liu R, Miller J |url = https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-of-roche-arthritis-drug-for-coronavirus-patients-idUSKBN20R0LF |title=China approves use of Roche drug in battle against coronavirus complications |date=3 March 2020 |work={{wipe|Reuters}} |access-date=14 March 2020 |archive-url=https://web.archive.org/web/20200312204625/https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-of-roche-arthritis-drug-for-coronavirus-patients-idUSKBN20R0LF |archive-date=12 March 2020 |url-status=live}}</ref><ref name="tocil-2">{{#invoke:cite journal ||vauthors = Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H |display-authors = 6 |title = Effective treatment of severe COVID-19 patients with tocilizumab |journal = Proceedings of the National Academy of Sciences of the United States of America |volume = 117 |issue = 20 |pages = 10970–10975 |date = May 2020 |pmid = 32350134 |pmc = 7245089 |doi = 10.1073/pnas.2005615117 |doi-access = free |title-link = doi |bibcode = 2020PNAS..11710970X }}</ref> It is undergoing a Phase{{spaces}}II non-randomised trial at the national level in Italy after showing positive results in people with severe disease.<ref>{{#invoke:Cite web||vauthors = Ovadia D, Agenzia Z |title=COVID-19 – Italy launches an independent trial on tocilizumab |url=https://www.univadis.co.uk/viewarticle/covid-19-italy-launches-an-independent-trial-on-tocilizumab-715741 |website=Univadis from Medscape |publisher=Aptus Health |access-date=22 April 2020}}</ref><ref>{{#invoke:Cite web||title=Tocilizumab in COVID-19 Pneumonia (TOCIVID-19) (TOCIVID-19) |url=https://clinicaltrials.gov/ct2/show/NCT04317092 |website=clinicaltrials.gov |access-date=22 April 2020}}</ref> Combined with a serum ferritin blood test to identify a cytokine storm (also called cytokine storm syndrome, not to be confused with cytokine release syndrome), it is meant to counter such developments, which are thought to be the cause of death in some affected people.<ref name="tocil-5,6,8">Various sources:
* {{#invoke:cite journal || vauthors = Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ | title = COVID-19: consider cytokine storm syndromes and immunosuppression | journal = Lancet | volume = 395 | issue = 10229 | pages = 1033–1034 | date = March 2020 | pmid = 32192578 | pmc = 7270045 | doi = 10.1016/S0140-6736(20)30628-0 | ref = none | title-link = doi | doi-access = free }}</ref> The [[Biology:Interleukin-6 receptor|interleukin-6 receptor]] (IL-6R) [[Biology:Receptor antagonist|antagonist]] was approved by the FDA to undergo a Phase{{spaces}}III clinical trial assessing its effectiveness on COVID‑19 based on retrospective case studies for the treatment of steroid-refractory cytokine release syndrome induced by a different cause, [[Biology:Chimeric antigen receptor T cell|CAR T cell]] [[Biology:Gene therapy|therapy]], in 2017.<ref name="CancerNetworkTocilizumabTrial">{{#invoke:Cite web|| vauthors = Slater H |title=FDA Approves Phase III Clinical Trial of Tocilizumab for COVID-19 Pneumonia |url=https://www.cancernetwork.com/news/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia |website=cancernetwork.com |date=26 March 2020 |publisher=Cancer Network |access-date=22 April 2020}}</ref> There is no randomised, controlled evidence that tocilizumab is an efficacious treatment for CRS. Prophylactic tocilizumab has been shown to increase serum IL-6 levels by saturating the IL-6R, driving IL-6 across the [[Biology:Blood–brain barrier|blood–brain barrier]], and exacerbating [[Chemistry:Neurotoxicity|neurotoxicity]] while having no effect on the incidence of CRS.<ref>{{#invoke:cite journal ||vauthors=Locke FL, Neelapu SS, Bartlett NL, Lekakis LJ, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Reagan PM, Bot A, Rossi JM, Sherman M, Navale L, Jiang Y, Aycock JS, Elias M, Wiezorek JS, Go WY, Miklos DB |display-authors=6 |title=Preliminary Results of Prophylactic Tocilizumab after Axicabtageneciloleucel (axi-cel; KTE-C19) Treatment for Patients with Refractory, Aggressive Non-Hodgkin Lymphoma (NHL) |journal=Blood |year=2017 |volume=130 |issue=Supplement 1 |pages=1547 |doi=10.1182/blood.V130.Suppl_1.1547.1547 |s2cid=155698207 |url=https://ashpublications.org/blood/article/130/Supplement%201/1547/79746}}</ref>

[[Chemistry:Lenzilumab|Lenzilumab]], an anti-GM-CSF [[Biology:Monoclonal antibody|monoclonal antibody]], is protective in murine models for CAR T cell-induced CRS and neurotoxicity and is a viable therapeutic option due to the observed increase of pathogenic GM-CSF secreting T{{spaces}}cells in hospitalised patients with COVID‑19.<ref>{{#invoke:cite journal || vauthors = Sterner RM, Sakemura R, Cox MJ, Yang N, Khadka RH, Forsman CL, Hansen MJ, Jin F, Ayasoufi K, Hefazi M, Schick KJ, Walters DK, Ahmed O, Chappell D, Sahmoud T, Durrant C, Nevala WK, Patnaik MM, Pease LR, Hedin KE, Kay NE, Johnson AJ, Kenderian SS | display-authors = 6 | title = GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR T cell function in xenografts | journal = Blood | volume = 133 | issue = 7 | pages = 697–709 | date = February 2019 | pmid = 30463995 | pmc = 6376281 | doi = 10.1182/blood-2018-10-881722 }}</ref>

==== Passive antibodies ====
[[File:Ppat.1008735.g002.png|thumb|Overview of the application and use of [[Medicine:Convalescent plasma|convalescent plasma]] therapy]]

Transferring purified and concentrated [[Medicine:Immunoglobulin therapy|antibodies]] produced by the immune systems of those who have recovered from COVID‑19 to people who need them is being investigated as a non-vaccine method of [[Biology:Passive immunity|passive immunisation]].<ref name="pmid-32167489">{{#invoke:cite journal || vauthors = Casadevall A, Pirofski LA | title = The convalescent sera option for containing COVID-19 | journal = The Journal of Clinical Investigation | volume = 130 | issue = 4 | pages = 1545–1548 | date = April 2020 | pmid = 32167489 | pmc = 7108922 | doi = 10.1172/JCI138003 }}</ref><ref name=":0">{{Cite journal |last1=Iannizzi |first1=Claire |last2=Chai |first2=Khai Li |last3=Piechotta |first3=Vanessa |last4=Valk |first4=Sarah J. |last5=Kimber |first5=Catherine |last6=Monsef |first6=Ina |last7=Wood |first7=Erica M. |last8=Lamikanra |first8=Abigail A. |last9=Roberts |first9=David J. |last10=McQuilten |first10=Zoe |last11=So-Osman |first11=Cynthia |last12=Jindal |first12=Aikaj |last13=Cryns |first13=Nora |last14=Estcourt |first14=Lise J. |last15=Kreuzberger |first15=Nina |date=2023-05-10 |title=Convalescent plasma for people with COVID-19: a living systematic review |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=5 |pages=CD013600 |doi=10.1002/14651858.CD013600.pub6 |issn=1469-493X |pmc=10171886 |pmid=37162745 |pmc-embargo-date=May 10, 2024 }}</ref> [[Biology:Neutralisation (immunology)|Viral neutralisation]] is the anticipated [[Chemistry:Mechanism of action|mechanism of action]] by which passive antibody therapy can mediate defence against SARS-CoV-2. The spike protein of SARS-CoV-2 is the primary target for neutralising antibodies.<ref name="Ho-2020">{{#invoke:cite journal || vauthors = Ho M | title = Perspectives on the development of neutralizing antibodies against SARS-CoV-2 | journal = Antibody Therapeutics | volume = 3 | issue = 2 | pages = 109–114 | date = April 2020 | pmid = 32566896 | pmc = 7291920 | doi = 10.1093/abt/tbaa009 | title-link = doi | doi-access = free }}</ref> As of 8{{spaces}}August 2020, eight neutralising antibodies targeting the spike protein of SARS-CoV-2 have entered clinical studies.<ref>{{#invoke:cite journal || vauthors = Yang L, Liu W, Yu X, Wu M, Reichert JM, Ho M | title = COVID-19 antibody therapeutics tracker: a global online database of antibody therapeutics for the prevention and treatment of COVID-19 | journal = Antibody Therapeutics | volume = 3 | issue = 3 | pages = 205–212 | date = July 2020 | pmid = 33215063 | pmc = 7454247 | doi = 10.1093/abt/tbaa020 }}</ref> It has been proposed that selection of broad-neutralising antibodies against SARS-CoV-2 and SARS-CoV might be useful for treating not only COVID‑19 but also future SARS-related CoV infections.<ref name="Ho-2020" /> Other mechanisms, however, such as [[Biology:Antibody-dependent cellular cytotoxicity|antibody-dependant cellular cytotoxicity]] or [[Biology:Phagocytosis|phagocytosis]], may be possible.<ref name="pmid-32167489" /> Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development.<ref name="pmid-32167489" />

The use of passive antibodies to treat people with active COVID{{nbhyph}}19 is also being studied. This involves the production of convalescent serum, which consists of the liquid portion of the blood from people who recovered from the infection and contains antibodies specific to this virus, which is then administered to active patients.<ref name="pmid-32167489" /> This strategy was tried for SARS with inconclusive results.<ref name="pmid-32167489" /> An updated Cochrane review in May 2023 found high certainty evidence that, for the treatment of people with moderate to severe COVID‑19, convalescent plasma did not reduce mortality or bring about symptom improvement.<ref name=":0" /> There continues to be uncertainty about the safety of convalescent plasma administration to people with COVID‑19 and differing outcomes measured in different studies limits their use in determining efficacy.<ref name=":0" />

=== Bioethics ===
Since the outbreak of the COVID‑19 pandemic, scholars have explored the [[Philosophy:Bioethics|bioethics]], [[Finance:Normative economics|normative economics]], and political theories of healthcare policies related to the public health crisis.<ref>{{#invoke:cite journal || vauthors = Maccaro A, Piaggio D, Pagliara S, Pecchia L | title = The role of ethics in science: a systematic literature review from the first wave of COVID-19 | journal = Health and Technology | volume = 11 | issue = 5 | pages = 1063–1071 | date = June 2021 | pmid = 34104626 | pmc = 8175060 | doi = 10.1007/s12553-021-00570-6|issn=2190-7188 }}</ref> Academics have pointed to the moral distress of healthcare workers, ethics of distributing scarce healthcare resources such as ventilators,<ref>{{#invoke:cite journal || vauthors = McGuire AL, Aulisio MP, Davis FD, Erwin C, Harter TD, Jagsi R, Klitzman R, Macauley R, Racine E, Wolf SM, Wynia M, Wolpe PR | display-authors = 6 | title = Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force | journal = The American Journal of Bioethics | volume = 20 | issue = 7 | pages = 15–27 | date = July 2020 | pmid = 32511078 | doi = 10.1080/15265161.2020.1764138 | s2cid = 219552665 }}</ref> and the global justice of vaccine diplomacies.{{citation needed|date=November 2021}} The socio-economic inequalities between genders,<ref>{{#invoke:cite journal || vauthors = Wenham C, Smith J, Morgan R | title = COVID-19: the gendered impacts of the outbreak | journal = Lancet | volume = 395 | issue = 10227 | pages = 846–848 | date = March 2020 | pmid = 32151325 | pmc = 7124625 | doi = 10.1016/S0140-6736(20)30526-2 }}</ref> races,<ref>{{#invoke:cite journal || vauthors = Tolchin B, Hull SC, Kraschel K | title = Triage and justice in an unjust pandemic: ethical allocation of scarce medical resources in the setting of racial and socioeconomic disparities | journal = Journal of Medical Ethics | volume = 47 | issue = 3 | pages = 200–202 | date = October 2020 | pmid = 33067315 | doi = 10.1136/medethics-2020-106457 | s2cid = 223558059 }}</ref> groups with disabilities,<ref>{{#invoke:cite journal || vauthors = Sabatello M, Burke TB, McDonald KE, Appelbaum PS | title = Disability, Ethics, and Health Care in the COVID-19 Pandemic | journal = American Journal of Public Health | volume = 110 | issue = 10 | pages = 1523–1527 | date = October 2020 | pmid = 32816541 | pmc = 7483109 | doi = 10.2105/AJPH.2020.305837 }}</ref> communities,<ref>{{#invoke:cite journal || vauthors = Chin T, Kahn R, Li R, Chen JT, Krieger N, Buckee CO, Balsari S, Kiang MV | display-authors = 6 | title = US-county level variation in intersecting individual, household and community characteristics relevant to COVID-19 and planning an equitable response: a cross-sectional analysis | journal = BMJ Open | volume = 10 | issue = 9 | pages = e039886 | date = September 2020 | pmid = 32873684 | pmc = 7467554 | doi = 10.1136/bmjopen-2020-039886 }}</ref> regions, countries,<ref>{{#invoke:cite journal || vauthors = Elgar FJ, Stefaniak A, Wohl MJ | title = The trouble with trust: Time-series analysis of social capital, income inequality, and COVID-19 deaths in 84 countries | journal = Social Science & Medicine | volume = 263 | pages = 113365 | date = October 2020 | pmid = 32981770 | pmc = 7492158 | doi = 10.1016/j.socscimed.2020.113365 }}</ref> and continents have also drawn attention in academia and the general public.

== See also ==
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* [[Biology:Coronavirus diseases|Coronavirus diseases]], a group of closely related syndromes
* [[Biology:Disease X|Disease X]], a WHO term{{Clear}}

== References ==
{{reflist
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|refs=
<ref name=cochrane>{{cite journal | vauthors = Jefferson T, Dooley L, Ferroni E, Al-Ansary LA, van Driel ML, Bawazeer GA, Jones MA, Hoffmann TC, Clark J, Beller EM, Glasziou PP, Conly JM | display-authors = 6 | title = Physical interventions to interrupt or reduce the spread of respiratory viruses | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD006207 | date = January 2023 | pmid = 36715243 | pmc = 9885521 | doi = 10.1002/14651858.CD006207.pub6 }}</ref>
<ref name=royalsoc>{{cite journal | url=https://doi.org/10.1098/rsta.2023.0133 | doi=10.1098/rsta.2023.0133 | title=Effectiveness of face masks for reducing transmission of SARS-CoV-2: A rapid systematic review | date=2023 | last1=Boulos | first1=Leah | last2=Curran | first2=Janet A. | last3=Gallant | first3=Allyson | last4=Wong | first4=Helen | last5=Johnson | first5=Catherine | last6=Delahunty-Pike | first6=Alannah | last7=Saxinger | first7=Lynora | last8=Chu | first8=Derek | last9=Comeau | first9=Jeannette | last10=Flynn | first10=Trudy | last11=Clegg | first11=Julie | last12=Dye | first12=Christopher | journal=Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | volume=381 | issue=2257 | pmid=37611625 | pmc=10446908 | bibcode=2023RSPTA.38130133B }}</ref>
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}}

== Further reading ==
{{refbegin}}
* {{cite Q|Q98568681|doi-access = free | title-link = doi }}
* {{cite Q|Q104287299|doi-access = free | title-link = doi }} Scholia Q104287299.
{{refend}}

== External links ==

=== Health agencies ===
* [https://www.nhs.uk/conditions/coronavirus-covid-19/ Coronavirus (COVID‑19)] by the UK National Health Service (NHS)
* [https://www.cdc.gov/coronavirus/2019-ncov/index.html Coronavirus 2019 (COVID-19)] by the US Centers for Disease Control and Prevention (CDC)
* [https://www.who.int/emergencies/diseases/novel-coronavirus-2019 Coronavirus disease (COVID‑19)] [https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters Facts] by the [[Organization:World Health Organization|World Health Organization]] (WHO)

=== Directories ===
* [https://centerforinquiry.org/coronavirus/ Coronavirus Resource Center] at the [[Organization:Center for Inquiry|Center for Inquiry]]
* {{Curlie|Health/Conditions_and_Diseases/Respiratory_Disorders/COVID-19|COVID-19}}
* [https://www.firemountain.net/covid19.html COVID‑19 Information on FireMountain.net] {{Webarchive|url=https://web.archive.org/web/20220113160833/http://firemountain.net/covid19.html |date=13 January 2022 }}
* [https://openmd.com/directory/covid-19 COVID‑19 Resource Directory on OpenMD]

=== Medical journals ===
* [https://www.bmj.com/coronavirus BMJ's Coronavirus (covid‑19) Hub] by the [[Company:BMJ|BMJ]]
* [https://www.nejm.org/coronavirus Coronavirus (Covid‑19)] by ''The New England Journal of Medicine''
* [https://www.springernature.com/gp/researchers/campaigns/coronavirus Coronavirus (COVID‑19) Research Highlights] by [[Company:Springer Nature|Springer Nature]]
* [https://jamanetwork.com/journals/jama/pages/coronavirus-alert Coronavirus Disease 2019 (COVID‑19)] by ''JAMA''
* [https://www.thelancet.com/coronavirus COVID‑19 Resource Centre] by ''The Lancet''
* [https://novel-coronavirus.onlinelibrary.wiley.com/ Covid‑19: Novel Coronavirus] {{Webarchive|url=https://web.archive.org/web/20200924195411/https://novel-coronavirus.onlinelibrary.wiley.com/ |date=24 September 2020 }} by [[Company:Wiley (publisher)|Wiley Publishing]]
* [https://www.elsevier.com/connect/coronavirus-information-center Novel Coronavirus Information Center] by [[Company:Elsevier|Elsevier]]

=== Treatment guidelines ===

{{Subject bar
 |commons        = yes
 |d              = yes
 |n              = yes
 |q              = yes
 |v              = yes
 |portal1        = COVID-19
 |portal2        = Medicine
 |portal3        = Viruses
}}

{{medical resources| ICD10 = {{ICD10|U07.1}}, {{ICD10|U07.2}}}}
{{Respiratory pathology}}
{{Viral diseases}}

[[Category:Zoonoses]]

{{Sourceattribution|COVID-19|1}}