ABSTRACTIn the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to COVID-19 patients. The therapy has been deemed safe and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here we performed repeated analyses at one-month interval on 31 convalescent individuals to evaluate how the humoral responses against the SARS-CoV-2 Spike, including neutralization, evolve over time. We observed that receptor-binding domain (RBD)-specific IgG slightly decreased between six and ten weeks after symptoms onset but RBD-specific IgM decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing SARS-CoV-2 S wild-type or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after symptoms resolution.

Highlights d Three weeks after the first BNT162b2 dose, weak neutralizing antibodies are elicited d These antibodies have robust Fc-mediated effector functions d Vaccination of individuals previously infected boosts humoral and cellular responses d Strong correlations between T helper cell and humoral responses are observed

Highlights d Spike-specific IgM and IgA wane more rapidly than IgG after recovery d Fc-effector functions, but not neutralization, are sustained over time d SARS-CoV-2-specific B cell immunity persists despite overall antibody decline