tetano
Editor, Senior Moderator
Front Immunol
. 2025 Apr 22:16:1516756.
doi: 10.3389/fimmu.2025.1516756. eCollection 2025. Associations between type III interferons, obesity and clinical severity of COVID-19
Dana Alalwan[SUP] 1 [/SUP], Alejandro Abner Garcia Leon[SUP] 1 [/SUP], Gurvin Saini[SUP] 1 [/SUP], Colette Gaillard[SUP] 1 [/SUP], Riya Negi[SUP] 1 [/SUP], Camille Heckmann[SUP] 2 [/SUP], Grace Kenny[SUP] 1 [/SUP], Eoin Feeney[SUP] 1 3 [/SUP], Aoife G Cotter[SUP] 1 4 [/SUP], Christine Kelly[SUP] 1 4 [/SUP], Michael Carr[SUP] 5 6 [/SUP], Eoghan de Barra[SUP] 7 8 [/SUP], Obada Yousif[SUP] 9 [/SUP], Mary Horgan[SUP] 1 3 [/SUP], Corinna Sadlier[SUP] 10 [/SUP], Alan Landay[SUP] 11 [/SUP], Gabriel Gonzalez[SUP] 12 [/SUP], Patrick W G Mallon[SUP] 1 3 [/SUP]
Affiliations
Introduction: Severe COVID-19 is characterized by hyperimmune host responses contributing to airway damage and acute respiratory distress syndrome. Type III interferons (IFN), including IFN lambda 4 (IFNλ4), expressed in individuals harboring the rs368234815-ΔG allele, are implicated in host immune responses to viral infections, including SARS-CoV-2.
Methods: We investigated associations between IFNλ4 expression through genotyping and COVID-19 disease severity in 853 laboratory-confirmed SARS-CoV-2 cases enrolled in the All-Ireland Infectious Diseases Cohort. Additionally, we measured plasma levels of Type I, II and III IFN using quantitative immunoassays along with IFNλ4 expression and COVID-19 disease severity in a sub-group [n=321 (37.6%)] with samples available within 10 days of symptom onset. IFNλ4 was expressed in 382 (44.8%) but expression was not significantly associated with COVID-19 disease severity.
Results: Within the sub-group, we found no consistent associations between IFNλ4 expression and circulating IFNs. However, we observed significantly increased expression of IFNλ1 and IFNλ2 in severe COVID-19 (P<0.01), with IFNλ2 remaining significantly associated after adjustment for age, sex, ethnicity, and comorbidities, including obesity (BMI≥30 kg/m2) (P<0.001). Interestingly, although IFNλ2 levels were significantly higher in subjects with obesity, the association between higher IFNλ2 and COVID-19 disease severity was only observed in individuals without obesity (P<0.01).
Conclusion: These data reveal an important role for IFNλ2 as an immune correlate that predicts COVID-19 disease severity, which may be masked in those with obesity.
Keywords: COVID-19; IFNλ2; IFNλ4; SARS-CoV-2; interferons; obesity.
. 2025 Apr 22:16:1516756.
doi: 10.3389/fimmu.2025.1516756. eCollection 2025. Associations between type III interferons, obesity and clinical severity of COVID-19
Dana Alalwan[SUP] 1 [/SUP], Alejandro Abner Garcia Leon[SUP] 1 [/SUP], Gurvin Saini[SUP] 1 [/SUP], Colette Gaillard[SUP] 1 [/SUP], Riya Negi[SUP] 1 [/SUP], Camille Heckmann[SUP] 2 [/SUP], Grace Kenny[SUP] 1 [/SUP], Eoin Feeney[SUP] 1 3 [/SUP], Aoife G Cotter[SUP] 1 4 [/SUP], Christine Kelly[SUP] 1 4 [/SUP], Michael Carr[SUP] 5 6 [/SUP], Eoghan de Barra[SUP] 7 8 [/SUP], Obada Yousif[SUP] 9 [/SUP], Mary Horgan[SUP] 1 3 [/SUP], Corinna Sadlier[SUP] 10 [/SUP], Alan Landay[SUP] 11 [/SUP], Gabriel Gonzalez[SUP] 12 [/SUP], Patrick W G Mallon[SUP] 1 3 [/SUP]
Affiliations
- PMID: 40330483
- PMCID: PMC12052549
- DOI: 10.3389/fimmu.2025.1516756
Introduction: Severe COVID-19 is characterized by hyperimmune host responses contributing to airway damage and acute respiratory distress syndrome. Type III interferons (IFN), including IFN lambda 4 (IFNλ4), expressed in individuals harboring the rs368234815-ΔG allele, are implicated in host immune responses to viral infections, including SARS-CoV-2.
Methods: We investigated associations between IFNλ4 expression through genotyping and COVID-19 disease severity in 853 laboratory-confirmed SARS-CoV-2 cases enrolled in the All-Ireland Infectious Diseases Cohort. Additionally, we measured plasma levels of Type I, II and III IFN using quantitative immunoassays along with IFNλ4 expression and COVID-19 disease severity in a sub-group [n=321 (37.6%)] with samples available within 10 days of symptom onset. IFNλ4 was expressed in 382 (44.8%) but expression was not significantly associated with COVID-19 disease severity.
Results: Within the sub-group, we found no consistent associations between IFNλ4 expression and circulating IFNs. However, we observed significantly increased expression of IFNλ1 and IFNλ2 in severe COVID-19 (P<0.01), with IFNλ2 remaining significantly associated after adjustment for age, sex, ethnicity, and comorbidities, including obesity (BMI≥30 kg/m2) (P<0.001). Interestingly, although IFNλ2 levels were significantly higher in subjects with obesity, the association between higher IFNλ2 and COVID-19 disease severity was only observed in individuals without obesity (P<0.01).
Conclusion: These data reveal an important role for IFNλ2 as an immune correlate that predicts COVID-19 disease severity, which may be masked in those with obesity.
Keywords: COVID-19; IFNλ2; IFNλ4; SARS-CoV-2; interferons; obesity.