Association between the Seroprevalence of Antibodies against Seasonal Alphacoronaviruses and SARS-CoV-2 Humoral Immune Response, COVID-19 Severity, and Influenza Vaccination

The present study assesses the seroprevalence of antibodies against seasonal human alphacoronaviruses 229E and NL63 among adult patients infected with SARS-CoV-2, and its association with the humoral response to SARS-CoV-2 infection and its severity, and influenza vaccination. A serosurvey was conducted to quantify the presence of IgG antibodies against the nucleocapsid of 229E (anti-229E-N) and NL63 (anti-NL63-N), and anti-SARS-CoV-2 IgG antibodies (against nucleocapsid, receptor-binding domain, S2 domain, envelope, and papain-like protease) for 1313 Polish patients. The seroprevalence of anti-229E-N and anti-NL63 in the studied cohort was 3.3% and 2.4%. Seropositive individuals had a higher prevalence of anti-SARS-CoV-2 IgG antibodies, higher titers of the selected anti-SARS-CoV2 antibodies, and higher odds of an asymptomatic SARS-CoV-2 infection (OR = 2.5 for 229E and OR = 2.7 for NL63). Lastly, the individuals vaccinated against influenza in the 2019/2020 epidemic season had lower odds of seropositivity to 229E (OR = 0.38). The 229E and NL63 seroprevalence was below the expected pre-pandemic levels (up to 10%), likely due to social distancing, increased hygiene, and face masking. The study also suggests that exposure to seasonal alphacoronaviruses may improve humoral responses to SARS-CoV-2 while decreasing the clinical significance of its infection. It also adds to accumulating evidence of the favorable indirect effects of influenza vaccination. However, the findings of the present study are of a correlative nature and thereby do not necessarily imply causation.