Data indicate that nearly all immunocompetent persons develop an adaptive immune response following SARS-CoV-2 infection, triggering antiviral humoral and cellular immune responses via B and T cell-mediated immunity (46), respectively. In humans, the humoral response includes antibodies directed against S and N proteins. The S protein contains two subunits, S1 and S2. The S1 subunit contains the receptor-binding domain (RBD) that mediates binding of virus to susceptible cells. RBD is the main target for neutralizing antibodies. Antibodies—including IgM, IgG, and IgA—against S and its subunits can be detected in serum within 1-3 weeks after infection (7, 8). IgM and IgG antibodies can arise nearly simultaneously (7); however, IgM (and IgA) antibodies decay more rapidly than IgG (7, 9). The clinical significance of measuring serum IgA in SARS-CoV-2 infection is not known; however secretory IgA plays an important role in protecting mucosal surfaces against pathogens by neutralizing respiratory viruses, including SARS-CoV-2 (10).

IgG antibodies, including IgG against the S and N proteins, persist for at least several months in most persons, but the precise duration of time that antibodies persist after infection is unknown (11). Loss of previously detectable SARS-CoV-2 antibodies (seroreversion) has been reported among persons with mild disease (12). Persons with more severe disease appear to develop a more robust antibody response with IgM, IgG, and IgA, all achieving higher titers and exhibiting longer persistence (12, 13). The observed persistence of antibodies can vary by assay (14), and some studies have found that approximately 5%–10% of people do not develop detectable IgG antibodies following infection (15, 16). Although neutralizing antibodies might not be detected among patients with mild or asymptomatic disease (17), the humoral immune response appears to remain intact, even with loss of specific antibodies over time, because of the persistence of memory B-cells (18). SARS-CoV-2 neutralizing antibodies that inhibit viral replication in vitro mainly target the RBD (5, 6).  Efforts to better understand antibody kinetics, longevity of humoral immune responses, correlation of binding antibody levels to neutralizing antibodies, and serological surrogates of immune protection are dependent on wider availability of quantitative binding antibody assays that are standardized and traceable to an international standard (19).

SARS-CoV-2 reinfection has been documented (20, 21); however, studies indicate that persons with SARS-CoV-2 antibodies are less likely to experience subsequent infection or clinical disease than persons without antibodies. Investigations of outbreaks among people on a fishing vessel and at a summer camp in the United States found that persons with pre-existing SARS-CoV-2 antibodies were correlated with protection from subsequent infection (22, 23). In sequential outbreaks among staff and residents of two British nursing homes, persons who tested antibody-positive following the first outbreak were approximately 96% less likely to become infected during the second outbreak four months later (24). In a British prospective cohort study of persons with and without SARS-CoV-2 antibodies, the adjusted incidence rate ratio for subsequent infection was 0.11 among persons followed for a median of 200 days after a positive antibody test, compared with those who tested negative for SARS-CoV-2 antibodies (2). Another British cohort study found an 84% reduction in SARS-CoV-2 infection incidence over a seven-month period among persons who had tested antibody positive for SARS-CoV-2 or had prior infection documented by reverse transcription polymerase chain reaction (RT-PCR) (1). A large study in the United States of commercial laboratory results linked to medical claims data and electronic medical records found a 90% reduction in infection among persons with antibodies compared with persons without antibodies (25), and another study of U.S. military recruits found that seropositive persons had an 82% reduction in incidence of SARS-CoV-2 infection over a 6-week period (26). Experiments on non-human primates support the above observations in humans. Experimentally infected rhesus macaques that developed humoral and cellular immune responses were protected against reinfection when re-challenged 35 days later (27). Another study found that transfer of purified IgG from rhesus macaques infected with SARS-CoV-2 was effective in protecting naïve rhesus macaques from infection, and the threshold titers for protection, based upon binding and neutralizing antibodies, were determined. Analyses of data from two vaccine trials found that higher titers of neutralizing and anti-S binding antibodies correlated with more effective protection from infection (28, 29).

Taken together, these findings in humans and non-human primates suggest that SARS-CoV-2 infection and development of antibodies can result in some level of protection against SARS-CoV-2 reinfection. The extent and duration of protection have yet to be determined. While life-long immunity has not been observed with endemic seasonal coronaviruses (30), studies of persons infected with the SARS-CoV-1 and Middle East Respiratory Syndrome (MERS-CoV) coronaviruses demonstrated measurable antibody for 18–24 months following infection (31, 32), and neutralizing antibody was present for 34 months in a small study of MERS-CoV-infected patients (33). It is not known to what extent persons re-infected with SARS-CoV-2 might transmit SARS-CoV-2 to others or whether the clinical spectrum differs from that of primary infection.


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