Serological assays to measure dimeric IgA antibodies in SARS‐CoV‐2 infections

Abstract

AbstractCurrent serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA‐ELISA and dIgA‐multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID‐19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID‐19; (iii) a cross‐sectional panel with PCR‐confirmed SARS‐CoV‐2 infection with mild COVID‐19 (n = 199) and (iv) pre–COVID‐19 samples (n = 200). The dIgA‐ELISA and dIgA‐MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS‐CoV‐2 infection. Individuals with mild COVID‐19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID‐19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID‐19 infections are associated with sustained levels of plasma dIgA compared with mild cases.