Qualitative Changes in the SARS-CoV-2 Antibody Response in the Post-Infection Phase Impact the estimates of infections in Population-Based Seroprevalence Studies


Craig Fenwick, Antony Croxatto, Alix T. Coste, Florence Pojer, Cyril Andre, Celine Pellaton, Alex Farina, Jeremy Campos, David Hacker, Kelvin Lau, Berend Jan Bosch, Semira Gonseth Nussle, Murielle Bochud, Valerie D’Acremont Genton, Didier Trono, Gilbert Greub, Giuseppe Pantaleo

We 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.

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