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

This publication is part of the Human Cell Atlas (https://www.humancellatlas.org/publications/). The authors gratefully acknowledge the Sanger Cellular Genetics Informatics team, particularly A. Predeus and S. Murray for their assistance with aligning the published raw data from uninfected MS patients, as well as S. van Dongen, M. Prete, and Q. Lin for their help with online data hosting. We acknowledge the members of the Vento-Tormo and Ballestar groups for useful discussions. A.B. received additional support from a Gates Cambridge Scholarship. This research was funded/supported by the R+D+i project of the Spanish Ministry of Science and Innovation (grant number PID2020-117212RB-I00/ MICIN/AEI/10.13039/501100011033), the Chan Zuckerberg Initiative (grant 2020-216799) and Wellcome Sanger core funding (WT206194). This publication has been supported by the Unstoppable campaign of the Josep Carreras Leukaemia Foundation. B.G., F.J.C.-N., and N.K.W. were funded by Wellcome (206328/Z/17/Z), the MRC (MR/S036113/1), and the Aging Biology Foundation. 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.