Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Lee, Wen Shi; Selva, Kevin John; Davis, Samantha K.; Wines, Bruce D.; Reynaldi, Arnold; Esterbauer, Robyn; Kelly, Hannah G.; Haycroft, Ebene R.; Tan, Hyon-Xhi; Juno, Jennifer A.; Wheatley, Adam K.; Hogarth, P. Mark; Cromer, Deborah; Davenport, Miles P.; Chung, Amy W.; Kent, Stephen J.

The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We develop assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19, up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last timepoint studied (94%) in contrast with neutralisation activity (70%). While it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralising antibodies.