IFNA1 and COVID-19: On the one hand, the occurrence of genetic mutations in the IFN-I pathways or the presence of autoantibodies against IFN-I, which are partly associated with severe cases of SARS-CoV-2 infection, underline the protective role of IFN during SARS-CoV-2 infection; on the other hand, an early elevation in cytokine levels, including the IFN response, which is associated with worse COVID-19 outcomes, highlights its pathogenic role.