AbstractThe clinical course of COVID-19 is very heterogeneous: Most infected individuals can be managed in an outpatient setting, but a substantial proportion of patients requires intensive care, resulting in a high rate of fatalities. Recently, an association between contact to small children and mild course of COVID-19 was reported. We performed an observational study to assess the impact of previous infections with seasonal coronaviruses on COVID-19 severity. 60 patients with confirmed COVID-19 infections were included (age 30 - 82 years; 52 males, 8 females): 19 inpatients with critical disease, 16 inpatients with severe or moderate disease and 25 outpatients (age and gender matched to inpatients). Patients with critical disease had significantly lower levels of HCoV OC43- (p=0.016) and HCoV HKU1-specific (p=0.023) antibodies at the first encounter compared to other COVID-19 patients. Our results indicate that previous infections with seasonal coronaviruses might protect against a severe course of disease. This finding should be validated in other settings and could contribute to identify persons at risk before an infection.