Rapid decline of neutralizing antibodies is associated with decay of IgM in adults recovered from mild COVID-19

The fate of protective immunity following mild SARS-CoV-2 infection remains ill defined. Here we characterize antibody responses in a cohort of participants recovered from mild SARS-CoV-2 infection with follow up to 6 months. We measure IgA, IgM, and IgG binding and avidity to viral antigens and assess neutralizing antibody responses over time. Further, we correlate the effect of fever, gender, age, and time since symptom onset with antibody responses. We observe that total anti-S trimer, anti-RBD, and anti-NP IgG are relatively stable over 6 months of follow-up and anti-S and anti-RBD avidity increases over time, and that fever is associated with higher levels of antibodies. However, neutralizing antibody responses rapidly decay and are strongly associated with declines in IgM levels. Thus, while total antibody against SARS-CoV-2 may persist, functional antibody, particularly IgM, is rapidly lost. These observations have implications for the duration of protective immunity following mild SARS-CoV-2 infection.
Graphical Abstract
Harrington et al., report that in adults with mild COVID-19, IgG responses are maintained for over six months and are correlated with fever. Neutralization activity rapidly decays, correlating with the loss of anti-S-trimer IgM titers. Thus, neutralizing antibodies fade quickly after mild COVID-19 infection, despite the long-term maintenance of IgG.