Within this context, we report here a multiomics analysis of systemic IFN signaling in hospitalized COVID-19 patients, including a comprehensive examination of the whole-blood transcriptome, plasma proteome, anti–SARS-CoV-2 antibodies, peripheral immune cell repertoire, plasma and red blood cell (RBC) metabolomes, as well as immune and clinical markers of disease risk and severity in relationship to circulating levels of 12 different IFNs. The gene discussed is IFNA1; the disease is COVID-19.