Single-cell multi-omics analysis of COVID-19 patients with pre-existing autoimmune diseases shows aberrant immune responses to infection
Barmada, Anis (Department of Medical Genetics. University of Cambridge)
Handfield, Louis-François (Wellcome Sanger Institute (Regne Unit))
Godoy-Tena, Gerard (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
de la Calle-Fabregat, Carlos (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ciudad, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Arutyunyan, Anna (Wellcome Sanger Institute (Regne Unit))
Andrés-León, Eduardo (Instituto de Parasitología y Biomedicina "López-Neyra")
Hoo, Regina (Wellcome Sanger Institute (Regne Unit))
Porter, Tarryn (Wellcome Sanger Institute (Regne Unit))
Oszlanczi, Agnes (Wellcome Sanger Institute (Regne Unit))
Richardson, Laura (Wellcome Sanger Institute (Regne Unit))
Calero-Nieto, Fernando (Department of Haematology and Wellcome & MRC Cambridge Stem Cell Institute. University of Cambridge)
Wilson, Nicola K. (Department of Haematology and Wellcome & MRC Cambridge Stem Cell Institute. University of Cambridge)
Marchese, Domenica (Centre de Regulació Genòmica)
Sancho-Serra, Carmen (Wellcome Sanger Institute. Wellcome Genome Campus)
Carrillo, Jorge (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Presas-Rodríguez, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ramo-Tello, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ruiz-Sanmartin, Adolfo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ferrer, Ricard (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ruiz-Rodriguez, Juan Carlos (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez Gallo, Mónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Munera-Campos, Monica (Institut Germans Trias i Pujol)
Carrascosa, José Manuel (Institut Germans Trias i Pujol)
Göttgens, Berthold (Department of Haematology and Wellcome & MRC Cambridge Stem Cell Institute. University of Cambridge)
Heyn, Holger (Universitat Pompeu Fabra)
Prigmore, Elena (Wellcome Sanger Institute (Regne Unit))
Casafont-Solé, Ivette (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Solanich, Xavier (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sánchez-Cerrillo, Idelfonso (Department of Immunology. Hospital Universitario La Princesa)
González-Álvaro, Isidoro (Rheumatology Service. Hospital Universitario La Princesa)
Raimondo, Maria Gabriella (Deutsches Zentrum Immuntherapie. Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen)
Ramming, Andreas (Deutsches Zentrum Immuntherapie. Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen)
Martin, Javier (Instituto de Parasitología y Biomedicina "López-Neyra")
Martínez Cáceres, Eva María (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Ballestar, Esteban (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Vento-Tormo1, Roser (Wellcome Sanger Institute. Wellcome Genome Campus)
Rodríguez-Ubreva, Javier (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Data:	2024
Resum:	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.
Ajuts:	Ministerio de Ciencia e Innovación PID2020-117212RB-I00
Nota:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Autoimmunity ; COVID-19 ; Multiple sclerosis ; Psoriasis ; Rheumatoid arthritis
Publicat a:	European Journal of Immunology, Vol. 54 Núm. 1 (january 2024) , p. 2350633, ISSN 1521-4141

DOI: 10.1002/eji.202350633

18 p, 3.4 MB

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