COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation

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 immu...

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Autores: Rodríguez-Ubreva, Javier|||0000-0003-4707-4536, Calafell-Segura, Josep|||0000-0002-0173-8221, Calvillo, Celia L., Keller, Baerbel, Ciudad, Laura|||0000-0002-5219-6792, Handfield, Louis-François, de la Calle-Fabregat, Carlos|||0000-0002-3026-3069, Godoy-Tena, Gerard|||0000-0003-3832-5794, Andrés-León, Eduardo|||0000-0002-0621-9914, Hoo, Regina, Porter, Tarryn|||0000-0002-6063-0659, Prigmore, Elena|||0000-0001-8870-0316, Hofmann, Maike|||0000-0001-8410-8833, Decker, Annegrit, Martín, Javier|||0000-0002-2202-0622, Vento Tormo, Roser|||0000-0002-9870-8474, Warnatz, Klaus|||0000-0002-1172-865X, Ballestar, Esteban|||0000-0002-1400-2440
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:309342
Acceso en línea:https://ddd.uab.cat/record/309342
https://dx.doi.org/urn:doi:10.1038/s41467-024-54732-x
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario: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.

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