ABSTRACT
Background: SARS-CoV-2 infection leads to a broad range of clinical manifestations, from no symptoms to critical illness. Pre-stimulated innate defenses, rapid induction of SARS-CoV-2 responses and pre-existing crossreactive immunity to circulating human coronaviruses (HCoV) may early dampen SARS-CoV-2 infection, preventing symptomatic disease. Here we explore SARS-CoV-2 and HCoV antibody impact on asymptomatic infection in individuals first encountering SARS-CoV-2 in March 2020-March 2021 participating in a longitudinal pediatric cohort (n=2917) and a cross-sectional adult and children diagnostic cohort (n=882) in Switzerland. Method(s): Antibodies (Ab) to S1 of the four HCoV strains and SARS-CoV-2 antigens S1, RBD, S2 and N were determined in saliva (n=4993) and serum (n=7486) samples. Mucosal and systemic neutralization activity against wildtype SARS-CoV-2-Wuhan, and Alpha, Delta and Omicron (BA.2) variants of concerns (VoC) was assessed by pseudovirus neutralization in a subset of individuals. Result(s): Analysis of simultaneously sampled saliva and plasma revealed a strong correlation of mucosal and systemic SARS-CoV-2 anti-spike responses in recent infection. Notably, pre-existing high HCoV antibody response was significantly associated with higher systemic (IgG, IgA, and IgM, p< 0.001) and mucosal (IgG, p=0.03) SARS-CoV-2 responses following SARS-CoV-2 infection. Adjusting for age and sex, we found four saliva SARS-CoV-2 Ab parameters, namely total Ig S2, total Ig S1, IgA S2 and IgM S1 (p< 0.001, p< 0.001, p=0.02, p=0.01 respectively), inversely associated with salivary viral load highlighting the impact of mucosal Ab response on viral suppression. Saliva neutralization activity was modest but surprisingly broad, retaining same level activity against Wuhan, Alpha and Delta, but not Omicron BA.2, whereas plasma neutralization activity showed the typical decrease for all three VoCs compared to Wuhan. Most interestingly, asymptomatic individuals presented with higher IgG S2 antibody reactivity in saliva (p=0.03) and higher pre-existing HCoV-S1 IgG activity in plasma (HKU1, p=0.04) and saliva (total hCoV, p=0.02) suggesting immune factors that restrict disease severity. Conclusion(s): Focusing on a SARS-CoV-2 infection and vaccine naive population, our study reveals interdependencies of systemic and mucosal SARS-CoV-2 and HCoV immunity following primary SARS-CoV-2 infection and locates reactivities linked with reduced viral load and asymptomatic infection.