| Autor: |
Phan, Hoang Van, Tsitsiklis, Alexandra, Maguire, Cole P., Haddad, Elias K., Becker, Patrice M., Kim-Schulze, Seunghee, Lee, Brian, Chen, Jing, Hoch, Annmarie, Pickering, Harry, van Zalm, Patrick, Altman, Matthew C., Augustine, Alison D., Calfee, Carolyn S., Bosinger, Steve, Cairns, Charles B., Eckalbar, Walter, Guan, Leying, Jayavelu, Naresh Doni, Kleinstein, Steven H. |
| Zdroj: |
Science Translational Medicine; 4/17/2024, Vol. 16 Issue 743, p1-16, 16p |
| Abstrakt: |
Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics. We found that older age correlated with increased SARS-CoV-2 viral abundance upon hospital admission, delayed viral clearance, and increased type I interferon gene expression in both the blood and upper airway. We also observed age-dependent up-regulation of innate immune signaling pathways and down-regulation of adaptive immune signaling pathways. Older adults had lower naïve T and B cell populations and higher monocyte populations. Over time, older adults demonstrated a sustained induction of pro-inflammatory genes and serum chemokines compared with younger individuals, suggesting an age-dependent impairment in inflammation resolution. Transcriptional and protein biomarkers of disease severity differed with age, with the oldest adults exhibiting greater expression of pro-inflammatory genes and proteins in severe disease. Together, our study finds that aging is associated with impaired viral clearance, dysregulated immune signaling, and persistent and potentially pathologic activation of pro-inflammatory genes and proteins. Editor's summary: It is well-established that older adults are at increased risk of severe and fatal COVID-19, but the mechanisms underlying this susceptibility are not entirely clear. To better understand features associated with age and COVID-19 severity, Phan et al. comprehensively studied the immune response to SARS-CoV-2 in a large longitudinal clinical cohort. By integrating mass cytometry, serum proteomics, antibody assays, and transcriptional analysis, the authors found that age was associated with increased viral load, delayed viral clearance, and alterations to immune cell frequencies. Markers of disease severity, such as interleukin-6, were the most extreme in the oldest patients. Together, these data provide insight into why age is a major risk factor for severe COVID-19. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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