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The Convalescent Sera Option for Containing COVID-19

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The Convalescent Sera Option for Containing COVID-19 The convalescent sera option for containing COVID-19 Arturo Casadevall, Liise-anne Pirofski J Clin Invest. 2020. https://doi.org/10.1172/JCI138003. Viewpoint As of early 2020, humanity is confronting a pandemic in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 causes coronavirus disease, abbreviated as COVID-19. At the time of this writing, SARS-CoV-2 is spreading in multiple countries, threatening a pandemic that will affect billions of people. This virus appears to be a new human pathogen. Currently there are no vaccines, monoclonal antibodies (mAbs), or drugs available for SARS-CoV-2, although many are in rapid development and some may be available in a short time. This Viewpoint argues that human convalescent serum is an option for prevention and treatment of COVID-19 disease that could be rapidly available when there are sufficient numbers of people who have recovered and can donate immunoglobulin-containing serum. Passive antibody therapy Passive antibody therapy involves the administration of antibodies against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent. In contrast, active vaccination requires the induction of an immune response that takes time to develop and varies depending on the vaccine recipient. Thus, passive antibody administration is the only means of providing immediate immunity to susceptible persons. Passive antibody therapy has a storied history going back to the 1890s and was the only means of treating certain infectious diseases prior to the development of antimicrobial therapy in […] Find the latest version: https://jci.me/138003/pdf The Journal of Clinical Investigation VIEWPOINT The convalescent sera option for containing COVID-19 Arturo Casadevall1 and Liise-anne Pirofski2 1Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA. 2Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA. As of early 2020, humanity is confront- tection is viral neutralization. However, and provide protection against infection. ing a pandemic in severe acute respiratory other mechanisms may be possible, such Depending on the antibody amount and syndrome coronavirus 2 (SARS-CoV-2). as antibody-dependent cellular cytotoxic- composition, the protection conferred by SARS-CoV-2 causes coronavirus disease, ity and/or phagocytosis. Possible sources the transferred immunoglobulin can last abbreviated as COVID-19. At the time of of antibody for SARS-CoV-2 are human from weeks to months. this writing, SARS-CoV-2 is spreading in convalescent sera from individuals who multiple countries, threatening a pandemic have recovered from COVID-19, mAbs, Historical precedents that will affect billions of people. This virus or preparations generated in certain ani- In the early twentieth century convalescent appears to be a new human pathogen. Cur- mal hosts, such as genetically engineered sera was used to stem outbreaks of viral rently there are no vaccines, monoclonal cows that produce human antibody (4). diseases such as poliomyelitis (8), measles antibodies (mAbs), or drugs available for Although many types of preparations are (9, 10), mumps (11), and influenza (12). A SARS-CoV-2, although many are in rapid or will soon be under development, the retrospective meta-analysis of eight studies development and some may be available only antibody type that is currently avail- on the use of convalescent sera involving in a short time. This Viewpoint argues that able for immediate use is that found in 1703 patients during the 1918 H1N1 influ- human convalescent serum is an option for human convalescent sera (Figure 1). As enza virus pandemic suggested that those prevention and treatment of COVID-19 more individuals contract COVID-19 and who received serum had lower mortality disease that could be rapidly available recover, the number of potential donors (13). Although the efficacy of convalescent when there are sufficient numbers of peo- will continue to increase. sera varied with the virus and the study, ple who have recovered and can donate A general principle of passive antibody there was consensus at the time that this immunoglobulin-containing serum. therapy is that it is more effective when intervention was useful, and it was used in used for prophylaxis than for treatment numerous outbreaks. It is noteworthy that Passive antibody therapy of disease. When used for therapy, anti- historically, convalescent sera were devel- Passive antibody therapy involves the body is most effective when administered oped and used in many cases without the administration of antibodies against a given shortly after the onset of symptoms. The means to measure antibody titers or knowl- agent to a susceptible individual for the pur- reason for temporal variation in efficacy edge about viral serotypes, and in clinical pose of preventing or treating an infectious is not well understood but could reflect studies that did not meet modern criteria disease due to that agent. In contrast, active that passive antibody works by neutraliz- for randomization or blinding. vaccination requires the induction of an ing the initial inoculum, which is likely to More recently, convalescent serum immune response that takes time to develop be much smaller than that of established was used during viral epidemics. In the and varies depending on the vaccine recip- disease (5). Another explanation is that 2009–2010 H1N1 influenza virus pan- ient. Thus, passive antibody administration antibody works by modifying the inflam- demic, convalescent serum antibody is the only means of providing immediate matory response, which is also more eas- preparations obtained by apheresis were immunity to susceptible persons. Passive ily achieved during the initial immune used to treat individuals with severe H1N1 antibody therapy has a storied history going response, a stage that may be asymptom- 2009 infection requiring intensive care back to the 1890s and was the only means atic (6). As an example, passive antibody (14). Serum-treated individuals manifest- of treating certain infectious diseases prior therapy for pneumococcal pneumonia was ed reduced respiratory viral burden, serum to the development of antimicrobial thera- most effective when administered shortly cytokine responses, and mortality (14). py in the 1940s (1, 2). Experience from prior after the onset of symptoms, and there was Convalescent serum was also used in the outbreaks with other coronaviruses, such as no benefit if antibody administration was 2013 West African Ebola epidemic. A small SARS-CoV-1, shows that such convalescent delayed past the third day of disease (7). nonrandomized study in Sierra Leone sera contain neutralizing antibodies to the For passive antibody therapy to be revealed significantly longer survival for relevant virus (3). effective, a sufficient amount of anti- those treated with convalescent whole In the case of SARS-CoV-2, the antic- body must be administered. When giv- blood relative to those who received stan- ipated mechanism of action by which pas- en to a susceptible person, this antibody dard treatment (15). Two patients trans- sive antibody therapy would mediate pro- will circulate in the blood, reach tissues, ferred to the United States and treated with a combination of convalescent serum and an experimental drug also survived Conflict of interest: The authors have declared that no conflict of interest exists. Copyright: © 2020, American Society for Clinical Investigation. (16). There is anecdotal evidence from the Reference information: J Clin Invest. https://doi.org/10.1172/JCI138003. H5N1 (17, 18) and H7N9 (19) avian flu out- jci.org 1 VIEWPOINT The Journal of Clinical Investigation Figure 1. Schematic of the use of convalescent sera for COVID-19. An individual who is sick with COVID-19 and recovers has blood drawn and screened for virus-neutralizing antibodies. Following identification of those with high titers of neutralizing antibody, serum containing these virus-neutralizing anti- bodies can be administered in a prophylactic manner to prevent infection in high-risk cases, such as vulnerable individuals with underlying medical condi- tions, health care providers, and individuals with exposure to confirmed cases of COVID-19. Additionally, convalescent serum could potentially be used in individuals with clinical disease to reduce symptoms and mortality. The efficacy of these approaches is not known, but historical experience suggests that convalescent sera may be more effective in preventing disease than in the treatment of established disease. breaks that use of convalescent sera was 500 mL convalescent serum, resulting in istration is that it can prevent infection effective, with all patients surviving. a reduction in serum virus titer, and each and subsequent disease in those who are Although every viral disease and epi- survived (21). Three patients with MERS at high risk for disease, such as vulnera- demic is different, these experiences pro- in South Korea were treated with convales- ble individuals with underlying medical vide important historical precedents that cent serum, but only two of the recipients conditions, health care providers, and are both reassuring and useful as humani- had neutralizing antibody in their serum those with exposure to confirmed cases ty now confronts the COVID-19 epidemic. (22). The latter study highlights a chal- of COVID-19.
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