Background: SARS-CoV-2 infection can be detected indirectly by measuring the host immune response. Anti-viral antibody concentrations generally correlate with host protection and viral neutralization, but in rare cases, antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of COVID-19 and identify potential therapeutic targets. Methods: Sera (n=533) from patients with RT-PCR confirmed COVID-19 (n=153) were tested using a high-throughput quantitative IgM and IgG assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. Results: Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. Conclusions: High sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics and vaccine development.
Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity