tetano
Editor, Senior Moderator
Nat Commun
. 2024 Nov 28;15(1):10344.
doi: 10.1038/s41467-024-54732-x. COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation
Javier Rodríguez-Ubreva[SUP] #[/SUP][SUP] 1 [/SUP], Josep Calafell-Segura[SUP] #[/SUP][SUP] 2 [/SUP], Celia L Calvillo[SUP] #[/SUP][SUP] 2 [/SUP], Baerbel Keller[SUP] #[/SUP][SUP] 3 4 [/SUP], Laura Ciudad[SUP] 2 [/SUP], Louis-François Handfield[SUP] 5 [/SUP], Carlos de la Calle-Fabregat[SUP] 2 [/SUP], Gerard Godoy-Tena[SUP] 2 [/SUP], Eduardo Andrés-León[SUP] 6 [/SUP], Regina Hoo[SUP] 5 [/SUP], Tarryn Porter[SUP] 5 [/SUP], Elena Prigmore[SUP] 5 [/SUP], Maike Hofmann[SUP] 7 [/SUP], Annegrit Decker[SUP] 7 [/SUP], Javier Martín[SUP] 6 [/SUP], Roser Vento-Tormo[SUP] 8 [/SUP], Klaus Warnatz[SUP] 9 10 [/SUP], Esteban Ballestar[SUP] 11 12 [/SUP]
Affiliations
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.
. 2024 Nov 28;15(1):10344.
doi: 10.1038/s41467-024-54732-x. COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation
Javier Rodríguez-Ubreva[SUP] #[/SUP][SUP] 1 [/SUP], Josep Calafell-Segura[SUP] #[/SUP][SUP] 2 [/SUP], Celia L Calvillo[SUP] #[/SUP][SUP] 2 [/SUP], Baerbel Keller[SUP] #[/SUP][SUP] 3 4 [/SUP], Laura Ciudad[SUP] 2 [/SUP], Louis-François Handfield[SUP] 5 [/SUP], Carlos de la Calle-Fabregat[SUP] 2 [/SUP], Gerard Godoy-Tena[SUP] 2 [/SUP], Eduardo Andrés-León[SUP] 6 [/SUP], Regina Hoo[SUP] 5 [/SUP], Tarryn Porter[SUP] 5 [/SUP], Elena Prigmore[SUP] 5 [/SUP], Maike Hofmann[SUP] 7 [/SUP], Annegrit Decker[SUP] 7 [/SUP], Javier Martín[SUP] 6 [/SUP], Roser Vento-Tormo[SUP] 8 [/SUP], Klaus Warnatz[SUP] 9 10 [/SUP], Esteban Ballestar[SUP] 11 12 [/SUP]
Affiliations
- PMID: 39609471
- PMCID: PMC11605083
- DOI: 10.1038/s41467-024-54732-x
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.