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

Abstract

The capacity of antibodies to engage with innate and adaptive immune cells via the Fc region is important in preventing and controlling many infectious diseases, and is likely critical in SARS-CoV-2 infection. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We developed novel assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial samples from a cohort of 53 subjects primarily with mild-moderate COVID-19, out to a maximum of 149 days post-infection. We found that S-specific antibodies capable of engaging dimeric FcγRIIa and FcγRIIIa decayed linearly over time. S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declined linearly as well, in line with the decay of S-specific IgG. Although there was significant decay in S-specific plasma ADCC and ADP activity, they remained readily detectable by all assays in 94% of our cohort at the last timepoint studied, in contrast with neutralisation activity which was only detectable in 70% of our cohort by the last timepoint. Our results suggest that Fc effector functions such as ADCC and ADP could contribute to the durability of SARS-CoV-2 immunity, particularly late in convalescence when neutralising antibodies have waned. Understanding the protective potential of antibody Fc effector functions is critical for defining the durability of immunity generated by infection or vaccination.

Clinical predictors of SARS‐CoV‐2 neutralizing antibody titers in COVID‐19 convalescents: Implications for convalescent plasma donor recruitment

“…S‐specific antibody‐dependent cellular cytotoxicity (ADCC) and antibody‐dependent phagocytosis (ADP) activity within plasma decline linearly as well, in line with the decay of S‐specific IgG. Although there was significant decay in S‐specific plasma ADCC and ADP activity, they remained readily detectable by all assays in 94% at 149 days, in contrast to nAbs, which were only detectable in 70% 27 . While this does not mean at all that the convalescents are not protected from further exposures (having immunity from specific T‐lymphocytes), 28 this circumstance further increases the need for cost‐effective screening strategies.…”

Adaptive immunity to human coronaviruses is widespread but low in magnitude

“…Defining the extent of serological and/or cellular immunity required to protect individuals from reinfection or severe disease remains a key question in the SARS-CoV-2 pandemic. As neutralizing responses wane after CoV infection, it is likely that a combination of serum antibody and B cell / T cell memory provide longer-term protection from the recurrence of disease 12,13 . The study of hCoV-specific T and B cell memory can therefore provide a key preview into the development of durable, protective SARS-CoV-2 immunity.…”

Adaptive immunity to human coronaviruses is widespread but low in magnitude

“…As neutralising responses wane after CoV infection, it is likely that a combination of serum antibody and B-cell/T-cell memory provides longer-term protection from the recurrence of disease. 12,13 The study of hCoV-specific T-and Bcell memory can therefore provide a key preview into the development of durable, protective SARS-CoV-2 immunity.…”