The developed multiplex assay was applied to track the cross-reactivity of antibodies targeting SARS-CoV-2, to detect changes in the IgG repertoire after SARS-CoV-2 infection or vaccination, to estimate the incidence of IgM antibodies against other respiratory viruses, and to estimate the percentage of patients in a cohort of patients with severe COVID-19 with autoantibodies against type I IFNs. This evidence concerns the gene CD40LG and COVID-19.