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For more than four years, one question has dogged the fight against the new coronavirus: Why does this infection cause more severe symptoms in older people? Medical researchers around the world have uncovered some of the causes, but the whole picture remains unclear. But the question remains.
Since the start of the pandemic in 2020, it has been clear that older adults are at greater risk for severe and even fatal COVID-19 infection. However, the underlying mechanisms that make older adults more susceptible to infection have not always been clear, despite studies that have taken into account comorbidities such as diabetes, heart and lung diseases, and other chronic variabilities associated with aging that may worsen the symptoms of infection.
Scientists have previously attributed the increased risk of severe COVID-19 in aging societies to a dysregulated immune system, an age-related tendency for excessive blood clotting, and an overall decline in T and B cells, key members of the adaptive immune system. And while all of these factors may play a role, an inevitable question arises: why?
New multi-center clinical study, report in Science Translational Medicineprovides a comprehensive answer and solves some of the mystery surrounding the poor prognosis in older adults. Scientists at the University of California, San Francisco, and collaborators across the U.S., investigated the progression of infection by studying a large longitudinal clinical cohort of people, ranging from the very young to the very old.
“We evaluated the effects of aging on the host immune response in the blood and upper respiratory tract, as well as in the nasal microbiota,” reported Dr. Hoang Van Phan, lead author of the study.
Fan explained that the study was a prospective, multicenter cohort study of 1,031 “vaccinated” patients aged between 18 and 96, adding that all study subjects, regardless of age, had been hospitalized with COVID. The aim of the study, Fan said, was to see how age makes a difference in the response to SARS-CoV-2 infection.
Fan and his colleagues knew when they began their study that there is a correlation between age and a decreased ability to clear the virus, and that older patients are also more likely to have greater inflammatory and immune disruption in the body.
To make matters worse, epidemiological studies have long shown that older age itself is a major risk factor for severe COVID-19: adults aged 75 and older are 140 times more likely to die from COVID-19 than younger people.
However, despite strong epidemiological patterns, the core biological reasons behind the effects of aging remain unclear, including why older people tend to have higher concentrations of the virus. To understand why, the research team conducted a series of sophisticated tests to try to find answers.
“We conducted mass cytometry, serum protein profiling, anti-SARS-CoV-2 antibody testing, and blood and nasal transcriptomics,” Fan wrote in the paper, emphasizing that analysis of blood and nasal swab samples was key to the study because the virus is abundant in both the blood and upper respiratory tract. Their test results provided new data and a new level of understanding.
“Older age is correlated with higher SARS-CoV-2 viral load on admission, delayed viral clearance, and increased type I interferon gene expression in both the blood and upper respiratory tract,” Fan continued.
“We also observed an age-dependent upregulation of innate immune signaling pathways and downregulation of adaptive immune signaling pathways,” Fan said, explaining that while production of monocytes from the innate immune system increased, naive T cells and B cells from the adaptive immune system declined.
Unlike younger patients, older patients showed more active innate immune pathways and a persistent increase in pro-inflammatory genes and cytokines, suggesting that aging may impair the body’s ability to suppress inflammatory responses. Furthermore, biomarkers of disease severity, such as interleukin-6, were most prominent in the oldest patients. Taken together, these data provide insight into why age is a major risk factor for severe COVID, the team concluded.
“Our study finds that aging is associated with impaired viral clearance, dysregulated immune signaling, and persistent and potentially pathological activation of pro-inflammatory genes and proteins,” Fan added, suggesting that the new findings may pave the way for treatments specifically targeted at older people.
“These differences suggest that older adults with severe COVID-19 may respond differently, and perhaps more favorably, to immunomodulatory therapies targeting specific inflammatory cytokines.”
For more information:
Hoang Van Phan et al. Host-microbe multi-omics profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adj5154
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