Neutralising SARS-CoV-2 RBD-specific antibodies persist for at least six months independently of symptoms in adults

In spring 2020, at the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Europe, we set up an assay system for large-scale testing of virus-specific and neutralising antibodies including their longevity. We analysed the sera of 1655 adult employees for SARS-CoV-2-specific antibodies using the S1 subunit of the spike protein of SARS-CoV-2. Sera containing S1-reactive antibodies were further evaluated for receptor-binding domain (RBD)- and nucleocapsid protein (NCP)-specific antibodies in relation to the neutralisation test (NT) results at three time points over six months. We detect immunoglobulin G (IgG) and/or IgA antibodies reactive to the S1 protein in 10.15% (n = 168) of the participants. In total, 0.97% (n = 16) are positive for S1-IgG, 0.91% (n = 15) were S1-IgG- borderline and 8.28% (n = 137) exhibit only S1-IgA antibodies. Of the 168 S1-reactive sera, 8.33% (n = 14) have detectable RBD-specific antibodies and 6.55% (n = 11) NCP-specific antibodies. The latter correlates with NTs (kappa coefficient = 0.8660) but start to decline after 3 months. RBD-specific antibodies correlate most closely with the NT (kappa = 0.9448) and only these antibodies are stable for up to six months. All participants with virus-neutralising antibodies report symptoms, of which anosmia and/or dysgeusia correlate most closely with the detection of virus-neutralising antibodies. RBD-specific antibodies are most reliably detected post-infection, independent of the number/severity of symptoms, and correlate with neutralising antibodies at least for six months. They thus qualify best for large-scale seroepidemiological evaluation of both antibody reactivity and virus neutralisation. Antibodies are proteins produced by the immune system in response to viruses. Antibodies against SARS-CoV-2, the virus that causes COVID-19, can be detected in the blood of people that have been previously infected. Here, we aimed to profile the levels of antibodies over 6 months in a group of 1655 Austrian adults working for the same company, with some working on-site and some working at home. Looking specifically at antibodies against the protein on the surface of the virus known as S1, we find that these are detectable in around approximately 10% of our group of adults and, of this group, 8% have antibodies against a specific part of the protein that binds its receptor on target cells. We observe that this specific subset of antibodies are most likely to persist up to 6 months, to be correlated with ability to neutralise the virus, and are associated with ongoing loss of taste and smell. These findings might have implications for monitoring of immunity, by helping us to understand which types of antibodies remain detectable and functional over time and how these relate to symptoms. Wagner et al. carry out a longitudinal seroepidemiological study of SARS-CoV-2 antibodies in a cohort of adults from a large company in Vienna, Austria. In individuals positive for S1-reactive antibodies at baseline, RBD-specific antibodies are most likely to persist for six months and correlate most closely with SARS-CoV-2 neutralizing ability.