SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay

Abstract

Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

Rapid implementation of a cohort for the study of post-acute sequelae of SARS-CoV-2 infection/COVID-19

“…We included up to 8 months of follow-up data, in contrast to studies which have been limited to the weeks and months following the initial illness [10,12,27]. Lastly, we have focused on biological specimen collection to facilitate biologically oriented research, which has already begun [28,29].…”

SARS‐CoV‐2 antibody persistence in COVID‐19 convalescent plasma donors: Dependency on assay format and applicability to serosurveillance

“…The majority of studies have focused on durability of antibodies detected by commercial or lab-developed indirect IgG assays and neutralizing assays, with most studies documenting waning of antibodies following peak reactivity approximately 1 month post-seroconversion. 3,4,5,6,22 Multiple studies have also correlated the waning of binding assay reactivities, and particularly IgG assays with S1, RBD and NC antigens, relative to waning neutralizing antibodies to identify high throughput and low cost assays that could serve as proxies for live virus PRNT or pseudovirus RVPN assays. 13,23 These analyses have demonstrated variable correlations and predictive values of S1, RBD and NC-based immunoassays with waning neutralizing activity.…”

Long-Term Longitudinal Evaluation of Six Commercial Immunoassays for the Detection of IgM and IgG Antibodies against SARS CoV-2

“…Our study showed that ELISA IgG antiNP (Epitopes) is not appropriate for serological evaluation at late time points PSO due to decreased sensitivity. The drop in sensitivity six months PSO is due most likely to the high number of samples from patients with mild form of disease, as it was recently reported [31]. In order to have a better view of the immune status of the COVID-19 convalescent patients, the binding assays should be complemented by sera neutralization assays, which are currently performed for our cohort.…”