Impaired immune response drives age-dependent severity of COVID-19

Abstract: 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-γ response and excessive virus replication. Accordingly, adult IFN-γ receptor-deficient mice phenocopied the age-related disease severity, and supplementation of IFN-γ reversed the increased disease susceptibility of aged mice. Further, we show that therapeutic treatment with IFN-λ in adults and a combinatorial treatment with IFN-γ and IFN-λ 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-γ and IFN-λ

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Journal of experimental medicine. - 219, 12 (2022) , e20220621, ISSN: 1540-9538

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2022
• Creator: Beer, Julius ; Crotta, Stefania ; Breithaupt, Angele ; Ohnemus, Annette ; Becker, Jan ; Sachs, Benedikt ; Kern, Lisa ; Llorian, Miriam ; Ebert, Nadine ; Labroussaa, Fabien ; Nhu Thao, Tran Thi ; Trüeb, Bettina Salome ; Jores, Jörg ; Thiel, Volker ; Beer, Martin ; Fuchs, Jonas ; Kochs, Georg ; Wack, Andreas ; Schwemmle, Martin ; Schnepf, Daniel

Further information

• DOI: 10.1084/jem.20220621
• URN: urn:nbn:de:bsz:25-freidok-2298255
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:44 PM CET