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 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<sup>low</sup> B cells, impaired Th1 polarization, CD4<sup>+</sup> T central memory exhaustion, and increased CD8<sup>+</sup> 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.
Authors
- Baerbel Keller (ORCID: https://orcid.org/0000-0002-1491-6971)
- Roser Vento‐Tormo (ORCID: https://orcid.org/0000-0002-9870-8474)
- Josep Calafell-Segura (ORCID: https://orcid.org/0000-0002-0173-8221)
- Gerard Godoy‐Tena (ORCID: https://orcid.org/0000-0003-3832-5794)
- Annegrit Decker (ORCID: https://orcid.org/0000-0001-6413-8816)
- Klaus Warnatz (ORCID: https://orcid.org/0000-0002-1172-865X)
- Javier Rodríguez‐Ubreva (ORCID: https://orcid.org/0000-0003-4707-4536)
- Tarryn Porter (ORCID: https://orcid.org/0000-0002-6063-0659)
- Elena Prigmore (ORCID: https://orcid.org/0000-0001-8870-0316)
- Carlos de la Calle‐Fabregat (ORCID: https://orcid.org/0000-0002-3026-3069)
- Laura Ciudad (ORCID: https://orcid.org/0000-0002-5219-6792)
- Maike Hofmann (ORCID: https://orcid.org/0000-0001-8410-8833)
- Javier J. Martin (ORCID: https://orcid.org/0000-0002-2202-0622)
- Regina Hoo (ORCID: https://orcid.org/0000-0002-0295-9472)
- Eduardo Andrés‐León (ORCID: https://orcid.org/0000-0002-0621-9914)
- Esteban Ballestar (ORCID: https://orcid.org/0000-0002-1400-2440)
- Louis‐François Handfield
- Celia Lourdes Calvillo
Institutions
- Consejo Superior de Investigaciones Científicas (ES)
- University of Freiburg (DE)
- University Medical Center Freiburg (DE)
- Wellcome Sanger Institute (GB)
- Josep Carreras Leukaemia Research Institute (ES)
- Instituto de Parasitología y Biomedicina "López - Neyra" (ES)
- East China Normal University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1038/s41467-024-54732-x
- Citations
- 3
- Primary Topic
- Immunodeficiency and Autoimmune Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.72
Funders
- Wellcome Trust
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación