Increased SARS-CoV-2 viral load, an impaired ability to clear the virus, and weaker immune and anti-inflammatory responses may be why older adults are at higher risk for severe COVID-19 and death than younger people, a University of California at San Francisco–led research team posits in Science Translational Medicine.
The researchers also found that markers of illness severity such as the proinflammatory cytokine interleukin-6 were most highly concentrated in the oldest patients.
Adults older than 75 are 140 times more likely to die
The team prospectively tracked immune responses to SARS-CoV-2 in 2,523 blood, upper airway, and nasal swabs collected over time from 1,031 unvaccinated COVID-19 patients at 20 US hospitals participating in the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study from May 2020 to March 2021.Older adults were considered those 63 years and older.
The study authors point out that previous studies found that mild COVID-19 infection triggers more robust innate and adaptative immune responses in children than in adults. At the same time, among adults hospitalized for COVID-19, a stronger immune response leads to the development of severe disease, suggesting a complicated relationship between aging and host defense.
"Even with primary series vaccination rates above 90%, adults over 75 years of age are 140 times more likely to die if infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)," the study authors wrote. "Despite these epidemiological associations, the biological mechanisms underlying the impact of aging on COVID-19 remain incompletely understood."
Delayed viral clearance may lead to new variants
Older age corresponded with greater SARS-CoV-2 viral load at hospital admission, fewer immune cells, delayed viral clearance, increased pro-inflammatory type 1 interferon gene expression in the blood and upper airway, more active innate immune pathways, and a prolonged increase in pro-inflammatory genes and cytokines.
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.
The researchers said they saw age-dependent dysregulation of the immune response at the transcriptional, protein, and cellular levels, resulting in an imbalance of inflammatory responses during hospitalization.
"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," they wrote.
"These differences raise the possibility that older adults with severe COVID-19 may respond differently, and perhaps more favorably, to immunomodulatory therapies directed at certain inflammatory cytokines," they added. "Delayed viral clearance due to these age-related factors could facilitate the evolution of SARS-CoV-2 variants."
