For over four years, a crucial question has puzzled researchers in the fight against COVID-19: Why does the infection cause severe disease in older people?
Despite many studies shedding some light on this issue, the full picture remained unclear.
From the pandemic’s start in 2020, it was evident that older adults were at high risk of severe, even fatal COVID-19. Researchers considered factors like diabetes, heart and lung diseases, and other age-related conditions that could worsen infections.
They pointed to a dysregulated immune system, increased blood clotting, and a decline in vital immune cells like T and B cells as reasons for this heightened risk. Yet, the question “Why?” persisted.
A new multicenter clinical study reported in Science Translational Medicine offers comprehensive answers. Scientists from the University of California, San Francisco, along with collaborators across the United States, examined how COVID-19 progresses in different age groups. They studied a large group of people, ranging from the very young to the very old.
“We evaluated how aging impacts the immune response in the blood and upper airway, and in the nasal microbiome,” said Dr. Hoang Van Phan, the study’s lead author.
The study included 1,031 unvaccinated patients between 18 and 96 years old, all hospitalized for COVID-19. Phan and his team aimed to understand how age affected the body’s response to the virus.
They already knew that older patients had a harder time clearing the virus and experienced more severe disruptions in immune responses.
Epidemiological data had shown that older age was a significant risk factor for severe COVID-19. People over 75 were 140 times more likely to die from the disease than younger individuals.
Despite this clear pattern, the biological reasons remained elusive, especially why older people tended to have higher concentrations of the virus.
To uncover these reasons, the researchers performed a series of advanced tests. They used mass cytometry, serum protein profiling, anti–SARS-CoV-2 antibody assays, and blood and nasal transcriptomics. These tests revealed crucial new information.
“Older age correlated with more SARS-CoV-2 virus upon hospital admission, slower viral clearance, and higher type I interferon gene expression in both blood and the upper airway,” Phan explained.
The study found that the immune system’s response changes with age. Older patients had more active innate immune pathways and a persistent increase in pro-inflammatory genes and cytokines.
This suggested that aging might impair the body’s ability to shut down the inflammatory response. Biomarkers of disease severity, like interleukin-6, were highest in the oldest patients.
“Our study finds that aging is linked with impaired viral clearance, dysregulated immune signaling, and continuous activation of pro-inflammatory genes and proteins,” Phan noted. These findings might lead to new treatments specifically targeting older adults.
The results suggest that older adults with severe COVID-19 might respond better to therapies targeting specific inflammatory cytokines.
This study provides vital insights into why older people are more vulnerable to severe COVID-19 and highlights the importance of age-specific treatments.
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The research findings can be found in Science Translational Medicine.
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