Changes in SARS-CoV-2 Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies

Abstract

AbstractWe have determined SARS-CoV-2-specific antibody responses in a cohort of 96 individuals with acute infection and in 578 individuals enrolled in a seroprevalence population study in Switzerland including three groups, i.e. subjects with previous RT-PCR confirmed SARS-CoV-2 infections (n=90), ‘positive patient contacts’ (n=177) and ‘random selected subjects’ (n=311). SARS-CoV-2 antibody responses specific to the Spike (S), in the monomeric and native trimeric forms, and/or the nucleocapsid (N) proteins were equally sensitive in the acute infection phase. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection and substantially underestimated the proportion of SARS-CoV-2 infections in the groups of ‘patient positive contacts’, i.e. 10.9 to 32.2% reduction and in the ‘random selected’ general population, i.e. up to 45% reduction. The overall reduction in seroprevalence targeting only anti-N IgG antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was more sensitive as compared to monomeric S proteins.These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.