Medicine:Convalescent plasma

From HandWiki
Short description: Blood plasma from disease survivor

Convalescent plasma is the blood plasma collected from a survivor of an infectious disease. This plasma contains antibodies specific to a pathogen and can be used therapeutically by providing passive immunity when transfusing it to a newly infected patient with the same condition. Convalescent plasma can be transfused as it has been collected or become the source material for the hyperimmune serum which consists largely of IgG but also includes IgA and IgM. or as source material for anti-pathogen monoclonal antibodies, Collection is typically achieved by apheresis, but in low-to-middle income countries, the treatment can be administered as convalescent whole blood.

Methods of convalescent plasma collection, processing, and administration. Plasma is typically collected using apheresis. After collection, convalescent plasma may then be aliquoted before being stored and used for treatment. Alternatively, convalescent plasma may be pooled across many different donors and processed to pharmaceutical-grade convalescent plasma. Pathogen reduction technologies, such as solvent/detergent treatment or light treatment with additives can be employed to inactivate potential pathogens, including viruses, bacteria, protozoa, and leukocytes contaminating the plasma. Fractionation techniques may be used to create hyperimmune products. CP, convalescent plasma; HS, hyperimmune serum; PGCP, pharmaceutical-grade convalescent plasma; pharmaceutical-grade convalescent plasma; PRT, pathogen reduction technologies; S/D, solvent/detergent.

How it works

Antibodies

Specific antibodies to a pathogen are thought to be the primary driver of clinical benefit from convalescent plasma.[1] In the case of viral pathogens, the subset of antibodies that retain most of the activity is the one that drives viral neutralization, i.e. neutralizing antibodies, which can be quantified in a viral neutralization assay. This belief is based on dose-response clinical studies demonstrating that clinical benefit is directly related to the content of neutralizing antibodies,[2][3][4][5] and mechanistic studies that have established the antiviral activity of antibodies in convalescent plasma.[6][7] In addition to higher antibody concentrations being more effective, the timing of therapy is essential. Preparations are typically most effective when given prophylactically or early in the disease course (i.e. until pathogen replication persists or until the infected host's endogenous immune response develops).[8]

Other components of convalescent plasma

In addition to antibodies, convalescent plasma includes a mix of many different proteins and nonprotein factors that can occur in healthy individuals as well as develop in parallel with convalescence. These compounds may affect infection, coagulation, and inflammation independently of the effect of anti-pathogen antibodies.[1] Because convalescent plasma therapy is generally safe,[9] and the effects of neutralizing antibodies dominate the therapeutic response, the current understanding of these potential additional effects is limited and constitutes an area of ongoing research.[1]

Historical use of convalescent plasma

In 1890, Emil von Behring and Shibasaburo Kitasato used convalescent serum obtained from large mammals to treat infectious diseases and found that it was particularly effective at preventing and treating diphtheria.[10] Convalescent serum and plasma differ in that the former has all the coagulation components intact, but both are comparable regarding their antibody content. Hence, the older literature is focused on serum while today most preparations use plasma. Following the discovery by von Behring and Kitasato, antibody therapy garnered support worldwide as a treatment for infections. Von Behring was awarded the first Nobel Prize in Physiology or Medicine in 1901 for his discoveries.[10]

Before the development of antimicrobial treatment in the 1930s, antibody therapy in the form of serum therapy were the primary means of treating many bacterial and viral infections.[11] This treatment appears to have reduced the mortality of meningococcal meningitis,[12] pneumonia,[13] and erysipelas.[14] Additionally, antibody therapy seems to have been used successfully to prevent infection after exposure to measles,[15][16][17] mumps,[18] and chickenpox.[19]

1918 Influenza pandemic

The 1918 Spanish influenza pandemic was caused by an H1N1 influenza virus of avian origin, and around 500 million people, or one-third of the world's population, became infected with this virus.[20] The Spanish influenza pandemic was the first pandemic in which convalescent plasma was used as a therapy. A 2006 meta-analysis of eight studies from the Spanish influenza pandemic, including 1,703 patients, found that infected patients who received convalescent plasma had a 21% lower absolute mortality risk than patients not treated with convalescent plasma (16% vs. 37%).[21] Consistent with the general treatment principles of antiviral therapy, the most significant clinical and mortality benefits were noted among patients receiving convalescent serum in the early stages of the disease course.[21]

Modern use of convalescent plasma

After the introduction of antibiotics, the use of convalescent serum or plasma as a therapy for infectious diseases has been restricted mainly to replacement therapy for patients with immunoglobulin deficiencies[11] or in the context of viral epidemics or pandemics for which no widely available antiviral could be repurposed. Modern use has also included several randomized controlled trials providing conclusive evidence of efficacy. Selected viral epidemics or pandemics in which convalescent plasma has been used are reviewed below.

Argentine hemorrhagic fever

First identified in 1958, Argentine hemorrhagic fever is a rodent-borne illness caused by the arenavirus Junin that is endemic to the humid pampas of Argentina.[22] Convalescent plasma has been used during Argentine hemorrhagic fever epidemics; a double-blind, randomized clinical trial conducted from 1974 to 1978 demonstrated that patients treated with convalescent plasma within eight days of disease onset had a 15.4% lower absolute mortality rate than patients who received control plasma without neutralizing antibodies to Argentine hemorrhagic fever virus (1.1% vs. 16.5%).[23] Comparable results were described in subsequent outbreaks of Argentine hemorrhagic fever.[24]

2003 SARS epidemic (SARS-CoV-1)

In 2003, a novel coronavirus SARS-CoV-1 led to an epidemic of the severe acute respiratory syndrome.[25] Convalescent plasma was used to treat SARS;[26] in a retrospective analysis from Hong Kong that included 80 patients, early convalescent plasma treatment (14 days between the onset of symptoms and the transfusion date) was associated with an improved prognosis vs late transfusion (after 14 days since symptom onset) in terms of a higher hospital discharge rate by day 22 (58% vs 16%).[27] A review and meta-analysis that included eight observational studies (214 total patients) with SARS found a mortality benefit associated with convalescent plasma treatment.[28] Further studies were not conducted because the pandemic was extinguished.

2009–2010 influenza pandemic

In 2009, a particular influenza strain A(H1N1)pdm09 that evaded seasonal flu vaccines caused an influenza pandemic, which was referred to as the swine flu pandemic. Convalescent plasma was used to treat individuals with severe H1N1 infections requiring intensive care.[29] Despite usage very late in the disease course, patients treated with convalescent plasma had reduced respiratory viral burden, reduced serum cytokine responses, and reduced mortality.[29]

2012–2015 MERS epidemics

Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by the Middle East respiratory syndrome-related coronavirus (MERS-CoV), which is believed to have originated from bats.[30] The first identified case occurred in June 2012 in Jeddah, Saudi Arabia, and most cases have occurred in the Arabian Peninsula.[30] Convalescent plasma therapy has been used to treat MERS with mixed results; initial case reports and case series in the MERS epidemic failed to show a clinical benefit for patients transfused with convalescent plasma containing uncharacterized neutralizing antibody titers.[31] Consistent with the principle that higher antibody content in convalescent plasma results in improved efficacy, a subsequent study demonstrated that transfusion of convalescent plasma containing a high MERS-CoV neutralizing antibody titer resulted in detectable concentrations of antibodies in the blood of the recipient (seroconversion). However, seroconversion was not achieved in patients who received convalescent plasma with a low neutralizing antibody titer.[32] These findings highlight a challenge of convalescent plasma therapy, namely, that recovered survivors of viral diseases may not produce high-titer neutralizing antibodies, and thus not all convalescent plasma is equally potent.[33]

2013 Ebola epidemic

Ebola virus disease was discovered in 1976 when two consecutive outbreaks of fatal hemorrhagic fever occurred in different parts of Central Africa.[34] Convalescent plasma treatment was used during the 2013–2016 Ebola outbreak; a small nonrandomized study in Sierra Leone revealed significantly longer survival for patients treated with convalescent whole blood compared to patients receiving standard treatment.[35] Furthermore, two patients with Ebola who were transferred to the U.S. were treated with convalescent plasma, and an experimental small interfering RNA drug, and both survived their infections.[36]

2019 COVID-19 pandemic

In 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) spread rapidly around the globe after first being identified in Wuhan, China.[37] In early 2020, convalescent plasma started to be used in isolated cases and small series in China[38] and Italy.[39] Convalescent plasma therapy was deployed at scale in the United States through a Mayo Clinic-led Expanded Access Program for convalescent plasma[40] and a subsequent Emergency Use Authorization issued by the United States Food & Drug Administration.[41] Data from the Expanded Access Program demonstrated that among patients who were not mechanically ventilated, patients transfused with high-titer convalescent plasma had lower mortality than patients who received low-titer convalescent plasma (14.2% vs. 22.2%).[5] Relatively early during the pandemic, several randomized controlled trials concluded that convalescent plasma therapy was not effective for COVID-19,[42][43][44][45][46] but most of them focused on patients already seropositive or late in the disease course[42][43][44][45][46] and/or used plasma units with insufficient antibody levels.[44][47] Furthermore, there were methodological problems with some of the major trials raising concerns about the validity of negative results with regards to convalescent plasma efficacy.[48] Randomized controlled trials that instead focused on administering high-titer convalescent plasma early after diagnosis found that convalescent plasma treatment reduced hospital admission by ~50-80%,[4][49] which is in line with results achieved with monoclonal antibodies and small chemical antivirals.[50] Similarly, a randomized controlled trial that administered high-titer convalescent plasma in patients requiring mechanical ventilation found an absolute reduction in mortality of 14% in patients who received convalescent plasma within 48 hours of the initiation of mechanical ventilation.[51] Meta-analyses found that convalescent plasma treatment is associated with a mortality benefit,[52] particularly if it contains high antibody levels, is administered early, and in immunocompromised patients.[53] An epidemiologic analysis of convalescent plasma use and mortality in the United States showed a strong inverse correlation, providing strong evidence of efficacy at a population level.[54] From this data, it was estimated that the deployment of convalescent plasma had resulted in approximately 100,000 fewer deaths than had no plasma been used in the USA.[54]

In the post-vaccine COVID-19 pandemic, a resurgence in the usage of convalescent plasma occurred starting in the spring of 2022, when the SARS-CoV-2 variant Omicron sublineages proved non-responsive to all anti-spike monoclonal antibody treatments authorized,[55][56] and concerns emerged about contraindications and chronic exposure to small-chemical antivirals which had never been studied in immunocompromised patients at that point. Considering the urgent need to treat immunocompromised patients who were not protected after vaccination, the United States Food & Drug Administration re-authorized convalescent plasma for these patients;[57] accordingly, convalescent plasma was recommended in guidelines issued by the Infectious Disease Society of America[58] and the European Conference on Infections in Leukemia.[59] In the context of the wide deployment of COVID-19 vaccines, a unique product that can be collected from convalescent vaccinees, dubbed “hybrid plasma” or “Vax-plasma” has been of interest;[60] such double status creates heterologous immunity able to cross-react against any SARS-CoV-2 variant so far.[61]

An online petition was launched on April 27, 2022,[62] asking the World Health Organization to revise its guidelines issued in December 2021,[63] which discouraged convalescent plasma usage based on the evidence available until July 2021.[63]

Regulatory status

In the European Directorate for the Quality of Medicines and HealthCare guidelines for blood component manufacturing, no monography exists for convalescent plasma yet as of 2022. Outside clinical trials, the only way thus far to prescribe convalescent plasma is so-called compassionate usage, a procedure which requires authorization by a local ethical committee. In the United States, the use of convalescent plasma for the treatment of COVID-19 remains under Food & Drug Administration Emergency Use Authorization.

References

  1. ↑ 1.0 1.1 1.2 "COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors". Viruses 13 (8): 1594. August 2021. doi:10.3390/v13081594. PMID 34452459. 
  2. ↑ "Anti-Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After Plasma Infusion in Patients With Ebola Virus Disease". The Journal of Infectious Diseases 218 (4): 555–562. July 2018. doi:10.1093/infdis/jiy199. PMID 29659889. 
  3. ↑ "Compassionate use of convalescent plasma for treatment of moderate and severe pneumonia in COVID-19 patients and association with IgG antibody levels in donated plasma". eClinicalMedicine 26: 100525. September 2020. doi:10.1016/j.eclinm.2020.100525. PMID 32923991. 
  4. ↑ 4.0 4.1 "Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults". The New England Journal of Medicine 384 (7): 610–618. February 2021. doi:10.1056/NEJMoa2033700. PMID 33406353. 
  5. ↑ 5.0 5.1 "Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19". The New England Journal of Medicine 384 (11): 1015–1027. March 2021. doi:10.1056/NEJMoa2031893. PMID 33523609. 
  6. ↑ "Broad Neutralizing Activity Against Ebolaviruses Lacking the Mucin-Like Domain in Convalescent Plasma Specimens From Patients With Ebola Virus Disease". The Journal of Infectious Diseases 218 (suppl_5): S574–S581. November 2018. doi:10.1093/infdis/jiy302. PMID 29939289. 
  7. ↑ "Markers of Polyfunctional SARS-CoV-2 Antibodies in Convalescent Plasma". mBio 12 (2). April 2021. doi:10.1128/mBio.00765-21. PMID 33879585. 
  8. ↑ "The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19". mBio 12 (2). March 2021. doi:10.1128/mBio.03372-20. PMID 33653885. 
  9. ↑ "Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients". Mayo Clinic Proceedings 95 (9): 1888–1897. September 2020. doi:10.1016/j.mayocp.2020.06.028. PMID 32861333. 
  10. ↑ 10.0 10.1 "Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes". mBio 8 (1): e00117–17. February 2017. doi:10.1128/mBio.00117-17. PMID 28246359. 
  11. ↑ 11.0 11.1 "Return to the past: the case for antibody-based therapies in infectious diseases". Clinical Infectious Diseases 21 (1): 150–161. July 1995. doi:10.1093/clinids/21.1.150. PMID 7578724. 
  12. ↑ "The results of the serum treatment in thirteen hundred cases of epidemic meningitis". The Journal of Experimental Medicine 17 (5): 553–576. May 1913. doi:10.1084/jem.17.5.553. PMID 19867668. 
  13. ↑ "Serum therapy revisited: animal models of infection and development of passive antibody therapy". Antimicrobial Agents and Chemotherapy 38 (8): 1695–1702. August 1994. doi:10.1128/AAC.38.8.1695. PMID 7985997. 
  14. ↑ "The antitoxin treatment of erysipelas: further observations" (in en). Journal of the American Medical Association 99 (13): 1082. 1932-09-24. doi:10.1001/jama.1932.02740650040010. ISSN 0002-9955. 
  15. ↑ "Convalescent whole blood, plasma and serum in prophylaxis of measles" (in en). JAMA: The Journal of the American Medical Association 82 (15): 1180. 1924-04-12. doi:10.1001/jama.1924.02650410022011. ISSN 0098-7484. http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.1924.02650410022011. 
  16. ↑ "Pouvoir préventif du sérum d'un malade convalescent de rougeole". Bulletins et Mémoires de la Société Médicale des Hôpitaux de Paris 42 (337). 1918. 
  17. ↑ "Alcune esperienze di sieroimmunizzazione e sieroterapia nel morbillo". Rivista di Clinica e Pediatrica 5: 1017–1025. 1907. 
  18. ↑ "A protective therapy for mumps.". American Journal of Diseases of Children 10 (2): 99–103. August 1915. doi:10.1001/archpedi.1915.04110020024005. ISSN 1072-4710. https://zenodo.org/record/1500365. 
  19. ↑ "The prophylaxis of varicella with convalsecents' serum =" (in en). JAMA: The Journal of the American Medical Association 82 (16): 1245. April 1924. doi:10.1001/jama.1924.02650420009004. ISSN 0098-7484. 
  20. ↑ "The 1918 influenza pandemic: insights for the 21st century". The Journal of Infectious Diseases 195 (7): 1018–1028. April 2007. doi:10.1086/511989. PMID 17330793. 
  21. ↑ 21.0 21.1 "Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment?". Annals of Internal Medicine 145 (8): 599–609. October 2006. doi:10.7326/0003-4819-145-8-200610170-00139. PMID 16940336. 
  22. ↑ "Treatment of Argentine hemorrhagic fever". Antiviral Research 78 (1): 132–139. April 2008. doi:10.1016/j.antiviral.2007.10.010. PMID 18054395. 
  23. ↑ "Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome". Lancet 2 (8154): 1216–1217. December 1979. doi:10.1016/s0140-6736(79)92335-3. PMID 92624. 
  24. ↑ "[Treatment of Argentine hemorrhagic fever with convalescent's plasma. 4433 cases]". Presse Médicale 15 (45): 2239–2242. December 1986. PMID 2949253. 
  25. ↑ "Severe acute respiratory syndrome (SARS): a review". Clinical Medicine 4 (2): 152–160. March 2004. doi:10.7861/clinmedicine.4-2-152. PMID 15139736. 
  26. ↑ "Use of convalescent plasma therapy in SARS patients in Hong Kong". European Journal of Clinical Microbiology & Infectious Diseases 24 (1): 44–46. January 2005. doi:10.1007/s10096-004-1271-9. PMID 15616839. 
  27. ↑ "Use of convalescent plasma therapy in SARS patients in Hong Kong". European Journal of Clinical Microbiology & Infectious Diseases 24 (1): 44–46. January 2005. doi:10.1007/s10096-004-1271-9. PMID 15616839. 
  28. ↑ "The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis". The Journal of Infectious Diseases 211 (1): 80–90. January 2015. doi:10.1093/infdis/jiu396. PMID 25030060. 
  29. ↑ 29.0 29.1 "Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection". Clinical Infectious Diseases 52 (4): 447–456. February 2011. doi:10.1093/cid/ciq106. PMID 21248066. 
  30. ↑ 30.0 30.1 "The Middle East Respiratory Syndrome (MERS)". Infectious Disease Clinics of North America 33 (4): 891–905. December 2019. doi:10.1016/j.idc.2019.08.001. PMID 31668197. 
  31. ↑ "Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity". Scientific Reports 6: 25359. May 2016. doi:10.1038/srep25359. PMID 27146253. Bibcode: 2016NatSR...625359M. 
  32. ↑ "Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience". Antiviral Therapy 23 (7): 617–622. 2018. doi:10.3851/IMP3243. PMID 29923831. 
  33. ↑ "Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia". Emerging Infectious Diseases 22 (9): 1554–1561. September 2016. doi:10.3201/eid2209.151164. PMID 27532807. 
  34. ↑ "Ebola virus disease". Nature Reviews. Disease Primers 6 (1): 13. February 2020. doi:10.1038/s41572-020-0147-3. PMID 32080199. 
  35. ↑ "Evaluation of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra Leone". The Journal of Infection 74 (3): 302–309. March 2017. doi:10.1016/j.jinf.2016.11.009. PMID 27867062. 
  36. ↑ "The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States". Clinical Infectious Diseases 61 (4): 496–502. August 2015. doi:10.1093/cid/civ334. PMID 25904375. 
  37. ↑ "Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial". JAMA 324 (5): 460–470. August 2020. doi:10.1001/jama.2020.10044. PMID 32492084. 
  38. ↑ "Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma". JAMA 323 (16): 1582–1589. April 2020. doi:10.1001/jama.2020.4783. PMID 32219428. 
  39. ↑ "Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial". Haematologica 105 (12): 2834–2840. December 2020. doi:10.3324/haematol.2020.261784. PMID 33256382. 
  40. ↑ "Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study". PLOS Medicine 18 (12): e1003872. December 2021. doi:10.1371/journal.pmed.1003872. PMID 34928960. 
  41. ↑ US Food and Drug Administration (August 23, 2020). "FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment". https://www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-convalescent-plasma-potential-promising-covid-19-treatment. 
  42. ↑ 42.0 42.1 "A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia". The New England Journal of Medicine 384 (7): 619–629. February 2021. doi:10.1056/NEJMoa2031304. PMID 33232588. 
  43. ↑ 43.0 43.1 "Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial". Lancet 397 (10289): 2049–2059. May 2021. doi:10.1016/S0140-6736(21)00897-7. PMID 34000257. 
  44. ↑ 44.0 44.1 44.2 "Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)". BMJ 371: m3939. October 2020. doi:10.1136/bmj.m3939. PMID 33093056. 
  45. ↑ 45.0 45.1 "Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial". Trials 22 (1): 323. May 2021. doi:10.1186/s13063-021-05235-3. PMID 33947446. 
  46. ↑ 46.0 46.1 "Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial". JAMA 326 (17): 1690–1702. November 2021. doi:10.1001/jama.2021.18178. PMID 34606578. 
  47. ↑ "COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes". Clinical Microbiology Reviews 35 (3): e0020021. March 2022. doi:10.1128/cmr.00200-21. PMID 35262370. 
  48. ↑ "Convalescent plasma therapy in COVID-19: Unravelling the data using the principles of antibody therapy". Expert Review of Respiratory Medicine 17 (5): 381–395. May 2023. doi:10.1080/17476348.2023.2208349. PMID 37129285. 
  49. ↑ "Early Outpatient Treatment for Covid-19 with Convalescent Plasma". The New England Journal of Medicine 386 (18): 1700–1711. May 2022. doi:10.1056/NEJMoa2119657. PMID 35353960. 
  50. ↑ Template:Cite medRxiv
  51. ↑ "Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients". The New England Journal of Medicine 389 (17): 1590–1600. October 2023. doi:10.1056/NEJMoa2209502. PMID 37889107. 
  52. ↑ "Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis". Mayo Clinic Proceedings. Innovations, Quality & Outcomes 7 (5): 499–513. October 2023. doi:10.1016/j.mayocpiqo.2023.09.001. PMID 37859995. 
  53. ↑ "COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis". JAMA Network Open 6 (1): e2250647. January 2023. doi:10.1001/jamanetworkopen.2022.50647. PMID 36633846. 
  54. ↑ 54.0 54.1 "Convalescent plasma use in the USA was inversely correlated with COVID-19 mortality". eLife 10: e69866. June 2021. doi:10.7554/eLife.69866. PMID 34085928. 
  55. ↑ U.S. Food and Drug Administration (January 24, 2022). "Coronavirus (COVID-19) Update: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant". https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-limits-use-certain-monoclonal-antibodies-treat-covid-19-due-omicron. 
  56. ↑ U.S. Food and Drug Administration (March 30, 2022). "FDA updates Sotrovimab emergency use authorization". FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization. 
  57. ↑ U.S. Food & Drug Administration (January 2022). "Investigational COVID-19 Convalescent Plasma". https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-covid-19-convalescent-plasma. 
  58. ↑ Infectious Disease Society of America. "IDSA Guidelines on the Treatment and Management of Patients with COVID-19". https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/. 
  59. ↑ "Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)". Leukemia 36 (6): 1467–1480. June 2022. doi:10.1038/s41375-022-01578-1. PMID 35488021. 
  60. ↑ "Vax-Plasma in Patients With Refractory COVID-19". Mayo Clinic Proceedings 97 (1): 186–189. January 2022. doi:10.1016/j.mayocp.2021.11.001. PMID 34996552. 
  61. ↑ Template:Cite medRxiv
  62. ↑ National COVID-19 Convalescent Plasma Project. "Open letter to WHO for revisions to CCP recommendations". https://ccpp19.org/. 
  63. ↑ 63.0 63.1 "A living WHO guideline on drugs for covid-19". BMJ 370: m3379. September 2020. doi:10.1136/bmj.m3379. PMID 32887691. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Medicine:Convalescent_plasma&oldid=3268048"