SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

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

he earliest known case of SARS-CoV-2 infection causing COVID-19 is thought to have occurred on 17 November 2019 (ref. 1 ). As of 3 August 2021, 198.7 million confirmed cases of COVID-19 and 4.2 million deaths have been reported worldwide 2 . As the global scientific community has rallied in a concerted effort to understand SARS-CoV-2 infections, our background knowledge

Highlights d One mRNA vaccine dose induces robust humoral responses in convalescent donors d An extended interval between doses leads to high humoral responses in naive donors d These responses are stronger than in naive donors vaccinated with a short interval d Vaccine-elicited antibodies decline more rapidly in naive than convalescent donors Authors