COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation
Rodríguez-Ubreva, Javier (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Calafell-Segura, Josep (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Calvillo, Celia L. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Keller, Baerbel (University of Freiburg)
Ciudad, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Handfield, Louis-François (Wellcome Sanger Institute. Wellcome Genome Campus)
de la Calle-Fabregat, Carlos (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Godoy-Tena, Gerard (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Andrés-León, Eduardo (Instituto de Parasitología y Biomedicina "López-Neyra")
Hoo, Regina (Wellcome Sanger Institute. Wellcome Genome Campus)
Porter, Tarryn (Wellcome Sanger Institute. Wellcome Genome Campus)
Prigmore, Elena (Wellcome Sanger Institute. Wellcome Genome Campus)
Hofmann, Maike (University of Freiburg)
Decker, Annegrit (University of Freiburg)
Martín, Javier (Instituto de Parasitología y Biomedicina "López-Neyra")
Vento Tormo, Roser (Wellcome Sanger Institute. Wellcome Genome Campus)
Warnatz, Klaus (University of Freiburg)
Ballestar, Esteban (East China Normal University (ECNU))
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency, marked by hypogammaglobulinemia, poor antibody responses, and increased infection susceptibility. The COVID-19 pandemic provided a unique opportunity to study the effects of prolonged viral infections on the immune responses of CVID patients. Here we use single-cell RNA-seq and spectral flow cytometry of peripheral blood samples before, during, and after SARS-CoV-2 infection showing that COVID-19 CVID patients display a persistent type I interferon signature at convalescence across immune compartments. Alterations in adaptive immunity include sustained activation of naïve B cells, increased CD21 B cells, impaired Th1 polarization, CD4 T central memory exhaustion, and increased CD8 T cell cytotoxicity. NK cell differentiation is defective, although cytotoxicity remains intact. Monocytes show persistent activation of inflammasome-related genes. These findings suggest the involvement of intact humoral immunity in regulating these processes and might indicate the need for early intervention to manage viral infections in CVID patients.
Grants:	Agencia Estatal de Investigación PID2020-117212RB-I00
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Adaptive Immunity ; Adult ; B-Lymphocytes ; CD8-Positive T-Lymphocytes ; Common Variable Immunodeficiency ; Convalescence ; COVID-19 ; Disease Progression ; Female ; Humans ; Inflammasomes ; Interferon Type I ; Killer Cells, Natural ; Male ; Middle Aged ; SARS-CoV-2 ; Single-Cell Analysis
Published in:	Nature communications, Vol. 15 Núm. 1 (december 2024) , p. 10344, ISSN 2041-1723

DOI: 10.1038/s41467-024-54732-x
PMID: 39609471

21 p, 6.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles