Your browser doesn't support javascript.
Impaired immune response drives age-dependent severity of COVID-19.
Beer, Julius; Crotta, Stefania; Breithaupt, Angele; Ohnemus, Annette; Becker, Jan; Sachs, Benedikt; Kern, Lisa; Llorian, Miriam; Ebert, Nadine; Labroussaa, Fabien; Nhu Thao, Tran Thi; Trueeb, Bettina Salome; Jores, Joerg; Thiel, Volker; Beer, Martin; Fuchs, Jonas; Kochs, Georg; Wack, Andreas; Schwemmle, Martin; Schnepf, Daniel.
  • Beer J; Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
  • Crotta S; Immunoregulation Laboratory, The Francis Crick Institute, London, UK.
  • Breithaupt A; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Ohnemus A; Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
  • Becker J; Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
  • Sachs B; Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
  • Kern L; Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
  • Llorian M; Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK.
  • Ebert N; Institute of Virology and Immunology, Bern, Switzerland.
  • Labroussaa F; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Nhu Thao TT; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Trueeb BS; Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Jores J; Institute of Virology and Immunology, Bern, Switzerland.
  • Thiel V; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Beer M; Graduate School for Biomedical Science, University of Bern, Bern, Switzerland.
  • Fuchs J; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Kochs G; Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Wack A; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Schwemmle M; Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Schnepf D; Institute of Virology and Immunology, Bern, Switzerland.
J Exp Med ; 219(12)2022 12 05.
Article in English | MEDLINE | ID: covidwho-2037305
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.
Subject(s)
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Jem.20220621

Similar

MEDLINE
LILACS
LIS
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Jem.20220621