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

Barmada A, Handfield LF, Godoy-Tena G, de la Calle-Fabregat C, Ciudad L, Arutyunyan A, Andrés-León E, Hoo R, Porter T, Oszlanczi A, Richardson L, Calero-Nieto FJ, Wilson NK, Marchese D, Sancho-Serra C, Carrillo J, Presas-Rodríguez S, Ramo-Tello C, Ruiz-Sanmartin A, Ferrer R, Ruiz-Rodriguez JC, Martínez-Gallo M, Munera-Campos M, Carrascosa JM, Göttgens B, Heyn H, Prigmore E, Casafont-Solé I, Solanich X, Sánchez-Cerrillo I, González-Álvaro I, Raimondo MG, Ramming A, Martin J, Martínez-Cáceres E, Ballestar E, Vento-Tormo R, Rodríguez-Ubreva J.

Eur J Immunol

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.

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