Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies

Abstract

A large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike IgG, IgA and IgM levels with the S-Flow assay and map IgG-targeted epitopes by Luminex. We also evaluated neutralization, complement deposition and Antibody-Dependent Cellular Cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.

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

“…At present, analyses of Fc-mediated functions of SARS-CoV-2 antibodies within COVID-19 convalescent subjects have focused upon cross-sectional analyses or short-term longitudinal studies up to 1 to 2 months post-symptom onset. 16,19,20 We extend these findings and analyze Fc effector functions mediated by S-specific antibodies in a cohort of 53 convalescent individuals up to 149 days postsymptom onset. We developed functional assays using SARS-CoV-2 S-expressing cells to comprehensively analyze plasma ADCC and ADP activity against SARS-CoV-2 S. Our results show that plasma ADCC and ADP activity decays over the first 4 months post-infection, mirroring the decline in S-specific IgG titers.…”

“…Although neutralizing antibodies are likely to form a correlate of protection for SARS-CoV-2, 7,32 several studies find that neutralizing antibodies in convalescent donors with mild COVID-19 wane rapidly. 2,8,9 The rapid decline of plasma neutralization activity in the early weeks following infection is likely in part explained by the rapid decline of plasma IgM and IgA titers against S and RBD, 20,33 which substantially contribute to neutralization of SARS-CoV-2. [34][35][36] Given the relative scarcity of re-infection cases reported to date, it is likely that immune responses beyond neutralization, including antibody Fc effector functions and T cell responses, contribute to long-term protection from SARS-CoV-2.…”

How long does covid-19 immunity last?

“…Neutralising antibodies are expected to decline in number over time, says Timothée Bruel, a researcher at the Pasteur Institute, given what we know about the immune response to other infections. In April, Bruel and colleagues published a paper in Cell Reports Medicine that looked at antibody levels and functions in people who had experienced symptomatic or asymptomatic covid-19 6. Both types of participant possessed polyfunctional antibodies, which can neutralise the virus or assist in killing infected cells, among other things.…”

The second dose of the BNT162b2 mRNA vaccine does not boost SARS-CoV-2 neutralizing antibody response in previously infected subjects

“…A significant boost of naturally acquired immunity occurs with the first dose, although it remains to be established whether this increase translates into improved protection from reinfection or simply reflects the secondary immune response to recall antigen which would be protective per se. While the previously infected group in this study had asymptomatic or mild SARS-CoV-2 infection, subjects experiencing more symptoms are expected to develop higher NtAb titers on their own [ 4 ], thus a benefit from a second dose of vaccine is even more unlikely for this patient population. Strengths of the study are the test used (an authentic virus neutralization with a SARS-CoV-2 isolate circulating in Italy at HCW enrollment), the homogeneity of the study population and the very long interval, a median of 10 month, from recovery to NtAb titers measurement before first-dose vaccination.…”