Humoral response to spike S1 and S2 and nucleocapsid proteins on microarray after SARS‐CoV‐2 infection

Many aspects of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), such as its role in protection after natural infection, are still unclear. We evaluated IgA and IgG response to spike subunits 1 and 2 (S1 and S2) and Nucleocapsid proteins of SARS‐COV‐2 in serum samples of 109 volunteers with viral RNA detected or seroconversion with different clinical evolution (asymptomatic, mild, moderate, and severe coronavirus disease 2019), using the ViraChip® Test Kit. We observed that the quantification of antibodies to all antigens had a positive correlation to disease severity, which was strongly associated with the presence of comorbidities. Seroreversion was not uncommon even during the short (median of 77 days) observation, occurring in 15% of mild‐asymptomatic cases at a median of 55 days for IgG and 46 days for IgA. The time to reach the maximal antibody response did not differ significantly among recovered and deceased volunteers. Our study illustrated the dynamic of anti‐S1, anti‐N, and anti‐S2 IgA and IgG antibodies, and suggests that high production of IgG and IgA does not guarantee protection to disease severity and that functional responses that have been studied by other groups, such as antibody avidity, need further attention. Highlights Symptomatic SARS‐CoV‐2 infection generally elicits strong humoral immune response. IgA and IgG titers to three viral antigens (S1, S2 and N) correlate to severity of COVID‐19 disease. Seroreversion is not uncommon and may occur few months after SARS‐CoV‐2 infection. Elucidation of functional characteristics of antibodies are necessary to better understand disease pathogenesis and may guide vaccine boosting strategies.