biostudies-literatureRodriguez-Ubreva JWellcome Trust10344https://www.ebi.ac.uk/biostudies/studies/S-EPMC11605083biostudies-literatureUnknown15(1)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^low B cells, impaired Th1 polarization, CD4⁺ T central memory exhaustion, and increased Nature communicationsCOVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation.PMC11605083206194 and 108413/A/15/Dde la Calle-Fabregat CPrigmore EHandfield LFHofmann MRodriguez-Ubreva JCalafell-Segura JCalvillo CLPorter TVento-Tormo RHoo RWarnatz KKeller BCiudad LMartin JAndres-Leon EBallestar EGodoy-Tena GDecker AfalseCOVID-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^low B cells, impaired Th1 polarization, CD4⁺ T central memory exhaustion, and increased 2024-01-01T00:00:00Z2024 Nov2025-04-18T16:02:03.495Z2025-04-07T02:59:12.452ZS-EPMC116050833960947110.1038/s41467-024-54732-x