Convalescent serum is the serum component of blood, containing pathogen-neutralizing antibodies, drawn from an individual who has recovered from infection, which is administered to others as disease prevention or treatment. After blood is drawn it is screened for pathogen-neutralizing antibodies to identify those with high titers. Historical experience suggests that convalescent sera are more effective as a prevention than as treatment for an established disease. As a treatment, it is more effective when administered shortly after symptoms develop.
The administration of convalescent serum is a passive antibody therapy, which provides immediate immunity to susceptible individuals that lasts from weeks to months. In contrast active vaccination requires about two weeks to produce an induction of an immune response where the body produces protective antibodies against the disease. One or more doses of an active vaccination can provide long-lasting protection for years or for life.
Convalescent sera therapy was used to treat poliomyelitis, measles, mumps, influenza and during the 1918 H1N1 influenza pandemic. Efficacy varied with the virus and the study, but at the time there was no means to measure antibody titers and knowledge about viral serotypes was not known and clinical studies did not meet current criteria. In the more recent 2009-2010 H1N1 influenza virus pandemic serum-treated individuals showed reduced respiratory viral burden, serum cytokine responses and mortality. Convalescent serum used in the 2013 West African Ebola epidemic showed longer survival. There is some evidence for convalescent sera being effective against coronavirus diseases SARS and MERS.
Risks associated with covalescent sera include transfer of another infectious disease agent, reactions to serum constituents such as serum sickness but modern blood banking techniques and screening for pathogens and matching blood types would lower these risks. In a therapeutic mode, there could be a risk for transfusion-related acute lung injury (TRALI). A theoretic risk is antibody-dependent enhancement of infection (ADE) which involves the enhancement of disease in the presence of certain antibodies. Mechanisms for ADE that have been described for coronaviruses include concern that antibodies to one type of coronavirus could enhance infection to another viral strain. Available evidence for convalescent sera administration to patients with SARS1 and MERS suggest it is safe. Another theoretical risk is that the administration of antibodies may attenuate the body’s own immune response and leave those individuals vulnerable to subsequent reinfection.
The use of convalescent sera has been suggested as an option for treating COVID-19 as people recover and are able to donate immunoglobulin-containing serum. The mechanism of action is expected to be viral neutralization but other mechanisms such as antibody-dependent cellular cytotoxicity and/or phagocytosis are also possible. Individuals that have recovered from COVID-19 or animal hosts such as genetically engineered cows that produce human antibody are possible sources of antibodies against SARS-CoV-2. Takeda Pharmaceutical is generating purified, high titer antibody preparations against SARS-CoV-2 from COVID-19 convalescent sera. In March, 2020 a team at Johns Hopkin University led by Arturo Casadevall received FDA approval to try convalescent sera to treat COVID-19 patients. Patients who recover from COVID-19 will be asked to donate their blood to process the sera. Other hospitals collaborating to try the technique include the Mayo Clinic, the Stanford University Medical Center and Albert Einstein College.
