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Aging in COVID-19: Vulnerability, immunity and intervention
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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic was first reported in Wuhan, China in December 2019, moved across the globe at an unprecedented speed, and is having a profound and yet still unfolding health and socioeconomic impacts. SARS-CoV-2, a β-coronavirus, is a highly contagious respiratory pathogen that causes a disease that has been termed the 2019 coronavirus disease (COVID-19). Clinical experience thus far indicates that COVID-19 is highly heterogeneous, ranging from being asymptomatic and mild to severe and causing death. Host factors including age, sex, and comorbid conditions are key determinants of disease severity and progression. Aging itself is a prominent risk factor for severe disease and death from COVID-19. We hypothesize that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults. Much remains to be learned about the immune responses to SARS-CoV-2 infection. We need to begin partitioning all immunological outcome data by age to better understand disease heterogeneity and aging. Such knowledge is critical not only for understanding of COVID-19 pathogenesis but also for COVID-19 vaccine development.
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“Infection with SARS-CoV-2 triggers a cytokine storm, inflammation, cellular senescence, age-related immunosenescence, as well as diminished physiological reserves in the respiratory system and other organs.276,277”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [276]
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Mutation and Epistasis in Influenza Virus Evolution
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Chronic Low-grade Inflammatory Phenotype (CLIP) and Senescent Immune Dysregulation
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Self-citationThe Challenges of Vaccine Development against a New Virus during a Pandemic
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Metadata
- Authors
- Chen, Y., Klein, S. L., Garibaldi, B. T., Li, H., Wu, C., Osevala, N. M., Li, T., Margolick, J. B., Pawelec, G., & Leng, S. X.
- Affiliations
- Guangdong Academy of Medical Sciences (CN)
- Johns Hopkins University (US)
- Pennsylvania State University (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Health Sciences North (CA)
- Corresponding author
- Leng, Sean X.
- ORCID
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 65
- Pages
- 101205
- ISSN
- 1568-1637 (ISSN-L)
- PMC
- PMC7604159
- OpenAlex
- W3095294553
- Cited by
- 1,007
- References
- 155
- Citations by year
- 2026: 39 · 2025: 88 · 2024: 184 · 2023: 273 · 2022: 264 · 2021: 159
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Ageing Research Reviews (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (U54 AG062333, R42AG054322, R01 AI108907, R21 AG059742)
- Milstein Medical Asian American Partnership Foundation
- U.S. Department of Defense (W911QY-20\u22129-0012, W911QY-20, 9-0012)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- COVID-19 pandemic, SARS-CoV-2, aging, immunosenescence, inflammaging, older adults, disease severity, immune response, comorbidities, sex differences, COVID-19 vaccine development, age-related immune decline
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Aged, Aging, China, Humans, Immunity, Coronavirus
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