ArticleThe Journal of experimental medicine2022
Impaired immune response drives age-dependent severity of COVID-19.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- Caspase-11-mediated hyperinflammation impairs CD8+ T cell immunity and viral clearance in severe SARS-CoV-2 infection.JCI insight · 2026Article
- Live attenuated vaccination protects aged chimeric ACE2 mice from severe SARS-CoV-2 pathogenicity in vivo.PLoS pathogens · 2026Article
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- Helminth infection modulates the immunogenicity of COVID-19 vaccines in mice without compromising protective efficacy.Frontiers in immunology · 2026Article
- Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection.Nature communications · 2025Article
- Time series modeling shows early lymphocyte decline predicts inflammatory rise and mortality in older adults with community acquired pneumonia.Scientific reports · 2025Article
- Article
- Airway epithelial SARS-CoV-2 infectious and repair responses: relationships to age, sex, and post-COVID pulmonary syndromes.bioRxiv : the preprint server for biology · 2025Article
- Diagnostic accuracy of smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF assay for diagnosis of subclinical tuberculosis: a retrospective multicenter study.Microbiology spectrum · 2025Article
- Single-cell transcriptomics reveals a compartmentalized antiviral interferon response in the nasal epithelium of mice.Journal of virology · 2025Article
- Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection.Journal of leukocyte biology · 2025Article
- Post-viral lung diseases: the microbiota as a key player.ERJ open research · 2025Review
- SARS-CoV-2 Productively Infects Human Hepatocytes and Induces Cell Death.Journal of medical virology · 2025Article
- Cerebrospinal fluid and serum cytokine profiles in severe viral encephalitis with implications for refractory status epilepticus: a retrospective observational study.Frontiers in immunology · 2025Observational
- Aging Selectively Alters PRR and ISG Expression in Endo- and Ecto-Cervical Stromal Fibroblasts From the Human Female Reproductive Tract.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Article
- mRNA vaccine-induced IgG mediates nasal SARS-CoV-2 clearance in mice.Molecular therapy. Nucleic acids · 2024Article
- IFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN.JCI insight · 2024Article
- Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality.Cell death and differentiation · 2024Article
- Interferon-Science (New York, N.Y.) · 2024Review
- Diverging patterns in innate immunity against respiratory viruses during a lifetime: lessons from the young and the old.European respiratory review : an official journal of the European Respiratory Society · 2024Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.