SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection

Havervall, S.; Jernbom Falk, A.; Klingstrom, J.; Ng, H.; Greilert Norin, N.; Gabrielsson, L.; Salomonsson, A.-C.; Isaksson, E.; Rudberg, A.-S.; Hellstrom, C.; Andersson, E.; Olofsson, J.; Skoglund, L.; Yousef, J.; Pin, E.; Christ, W.; Olausson, M.; Hedhammar, M.; Tegel, H.; Mangsbo, S.; Phillipson, M.; Manberg, A.; Hober, S.; Nilsson, P.; Thalin, C.

Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1972 healthcare workers, of which 386 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in the vast majority of participants, 98%, at least four months post infection, despite having had no or mild symptoms. These antibody levels did not differ from those found in 59 convalescent COVID-19 patients (p=0.7). Virus neutralization capacity was confirmed by microneutralization assay in 93% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 68% of previously anti-nucleocapsid IgG positive healthcare workers, and these four-month follow-up levels were substantially lower in healthcare workers than in convalescent COVID-19 patients (p=2*10-5). Our findings support a durable and functional humoral response after SARS-CoV-2 infection, even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.