Single‐cell multi‐omics analysis of COVID‐19 patients with pre‐existing autoimmune diseases shows aberrant immune responses to infection

In COVID‐19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre‐existing autoimmune conditions can therefore be at increased risk of severe COVID‐19 and/or associated sequelae, yet SARS‐CoV‐2 infection in this group has been little studied. Here, we performed single‐cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS‐CoV‐2 infection. We observed compositional differences between the autoimmune disease groups coupled with altered patterns of gene expression, transcription factor activity, and cell–cell communication that substantially shape the immune response under SARS‐CoV‐2 infection. While enrichment of HLA‐DRlow CD14+ monocytes was observed in all three autoimmune disease groups, type‐I interferon signaling as well as inflammatory T cell and monocyte responses varied widely between the three groups of patients. Our results reveal disturbed immune responses to SARS‐CoV‐2 in patients with pre‐existing autoimmunity, highlighting important considerations for disease treatment and follow‐up. Patients with autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) display diverging and aberrant immune responses to SARS‐CoV‐2 infection, including widespread alterations in immune cell composition and T‐cell clonal expansion as well as in gene expression patterns, transcription factor activity, and cell–cell communication.