Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and composed of IgG, IgA, and IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2–specific neutralizing antibodies in the serum, saliva, and bronchoalveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2–specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM, and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably 1 month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post-symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against reinfection and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.
SARS-CoV-2–specific IgA, IgM, and IgG antibodies were measured in 214 serum samples from 132 patients with the Maverick SARS-CoV-2 Multi-Antigen Serology Panel (Genalyte Inc., USA) according to the manufacturer’s instructions. The Maverick SARS-CoV-2 Multi-Antigen Serology Panel (Genalyte Inc.) is designed to detect antibodies to five SARS-CoV-2 antigens: nucleocapsid, spike S1 RBD, spike S1S2, spike S2, and spike S1, within a multiplex format based on photonic ring resonance technology (18, 19). This automated system detects and measures with good reproducibility (fig. S3) changes in resonance when antibodies bind to their respective antigens on the chip. Combined IgG and IgM antibodies showed 91% sensitivity and 98% specificity. Briefly, 10 μl of each serum sample was added to a sample well plate array containing required diluents and buffers, and the plate and chip were loaded in the instrument for chip equilibration with the diluent buffer to measure baseline resonance. The serum sample was then charged over the chip to bind specific antibodies to antigens present on the chip. The chip was then washed to remove low-affinity binders, and specific antibodies were detected with anti-IgG, anti-IgA, or anti-IgM secondary antibodies. Forty-three sera collected before December 2019 were analyzed to calculate cutoff values. Positivity was defined as a result above the 99th percentile.