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 the 1940s (1, 2). Experience from prior outbreaks with other coronaviruses, such as SARS-CoV-1, shows that such convalescent sera contain neutralizing antibodies to the relevant virus (3).

In the case of SARS-CoV-2, the anticipated mechanism of action by which passive antibody therapy would mediate protection is viral neutralization. However, other mechanisms may be possible, such as antibody-dependent cellular cytotoxicity and/or phagocytosis. Possible sources of antibody for SARS-CoV-2 are human convalescent sera from individuals who have recovered from COVID-19, mAbs, or preparations generated in certain animal hosts, such as genetically engineered cows that produce human antibody (4). Although many types of preparations are or will soon be under development, the only antibody type that is currently available for immediate use is that found in human convalescent sera (Figure 1). As more individuals contract COVID-19 and recover, the number of potential donors will continue to increase.

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 antibodies can be administered in a prophylactic manner to prevent infection in high-risk cases, such as vulnerable individuals with underlying medical conditions, 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.

A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease. When used for therapy, antibody is most effective when administered shortly after the onset of symptoms. The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculum, which is likely to be much smaller than that of established disease (5). Another explanation is that antibody works by modifying the inflammatory response, which is also more easily achieved during the initial immune response, a stage that may be asymptomatic (6). As an example, passive antibody therapy for pneumococcal pneumonia was most effective when administered shortly after the onset of symptoms, and there was no benefit if antibody administration was delayed past the third day of disease (7).

For passive antibody therapy to be effective, a sufficient amount of antibody must be administered. When given to a susceptible person, this antibody will circulate in the blood, reach tissues, and provide protection against infection. Depending on the antibody amount and composition, the protection conferred by the transferred immunoglobulin can last from weeks to months.