| First Author | Beer J | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 12 | PubMed ID | 36129445 |
| Mgi Jnum | J:330858 | Mgi Id | MGI:7343524 |
| Doi | 10.1084/jem.20220621 | Citation | Beer J, et al. (2022) Impaired immune response drives age-dependent severity of COVID-19. J Exp Med 219(12):e20220621 |
| abstractText | Severity of COVID-19 shows an extraordinary correlation with increasing age. We generated a mouse model for severe COVID-19 and show that the age-dependent disease severity is caused by the disruption of a timely and well-coordinated innate and adaptive immune response due to impaired interferon (IFN) immunity. Aggravated disease in aged mice was characterized by a diminished IFN-gamma response and excessive virus replication. Accordingly, adult IFN-gamma receptor-deficient mice phenocopied the age-related disease severity, and supplementation of IFN-gamma reversed the increased disease susceptibility of aged mice. Further, we show that therapeutic treatment with IFN-lambda in adults and a combinatorial treatment with IFN-gamma and IFN-lambda in aged Ifnar1-/- mice was highly efficient in protecting against severe disease. Our findings provide an explanation for the age-dependent disease severity and clarify the nonredundant antiviral functions of type I, II, and III IFNs during SARS-CoV-2 infection in an age-dependent manner. Our data suggest that highly vulnerable individuals could benefit from immunotherapy combining IFN-gamma and IFN-lambda. |
