In our study, we evaluated antibody levels against HCoV-OC43 S proteins and the correlation between cross-reactive antibody level against HCoV-OC43 and disease severity in COVID-19 patients at days 1–10 PSO (which stands for the acute phase of infection), which may comprehensively inform the role of previous exposures of seasonal coronaviruses in COVID-19 pathogenesis. The gene discussed is PROS1; the disease is COVID-19.