Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity

Abstract

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.

Longitudinal analysis of the humoral response to SARS-CoV-2 spike RBD in convalescent plasma donors

“…Initial diagnosis had been confirmed by public health authorities through either PCR or epidemiologic contact. All participants also met the donor selection criteria for plasma donation in use at Héma- Consistent with previous reports on the rate of seroconversion of COVID-19 patients (16)(17)(18), the overall proportion of our convalescent plasma donors (n=282) that were tested seronegative at the time of donation was 6.9%. However, we noted that this proportion increased to about 15% if we considered only donors who had waited for more than 11-12 weeks after symptoms onset before donating ( Table 1).…”

Antibody response to SARS-CoV-2 infection in humans: a systematic review

“…In line with the expected sequential appearance of antibody isotypes, the majority of studies reported detection of IgM followed by IgG. 15,23,39,40 Nevertheless, this finding was not consistent across all studies. One study measured time to seroconversion for IgA, IgM, and IgG and demonstrated detection of IgA and IgM simultaneously, followed by IgG.…”

Kinetics of SARS-CoV-2 Antibody Avidity Maturation and Association with Disease Severity

“…Most immunocompetent individuals with symptomatic infections develop detectable SARS-CoV-2 antibodies within 2 weeks of symptom onset. 1 The SARS-CoV-2 IgG antibody response is more robust in severe cases of COVID-19 at all time-points after seroconversion. 1 Preliminary findings suggest that the magnitude of the antibody response correlates with virus neutralizing power, but some hypothesize that the antibodies could promote disease progression.…”

“…1 The SARS-CoV-2 IgG antibody response is more robust in severe cases of COVID-19 at all time-points after seroconversion. 1 Preliminary findings suggest that the magnitude of the antibody response correlates with virus neutralizing power, but some hypothesize that the antibodies could promote disease progression. 2 Influential factors in the distinction between protective antibodies and those that promote pathology include antibody isotype, concentration, specificity, post-translational modifications, and avidity for the virus.…”