New Insights into Why Old Age Leads to Severe, Fatal COVID-19

From the onset of the pandemic, it was evident that older adults faced a significantly higher risk of severe COVID-19. While existing research has considered factors such as co-morbidities (diabetes, heart and lung diseases, and other chronic conditions), the underlying mechanisms have not been fully understood.

Scientists have attributed the increased risk to a dysregulated immune system, a tendency for excessive blood clotting, and a decline in T and B cells, the key components of the adaptive immune system. However, the question of "why" remained.

A recent multicenter clinical study published in Science Translational Medicine sheds new light on this issue. Researchers from the University of California, San Francisco, and other institutions across the U.S. conducted an extensive study on a diverse age group, ranging from the very young to the very old.

Dr. Hoang Van Phan, the lead author, explained that the study assessed the impact of aging on the immune response in the blood, upper airway, and nasal microbiome. This prospective cohort trial involved 1,031 unvaccinated patients aged 18 to 96, all hospitalized for COVID-19. The goal was to understand how age affected the body's response to SARS-CoV-2 infection.

The researchers confirmed that older age correlated with a reduced ability to clear the virus and more significant disruptions in inflammatory and immune responses. Epidemiological data has long shown that adults over 75 are significantly more likely to die from COVID-19 than younger individuals.

To uncover the biological reasons, the team conducted advanced tests, including mass cytometry, serum protein profiling, antibody assays, and blood and nasal transcriptomics. They found that older patients had higher viral loads, delayed viral clearance, and increased expression of type I interferon genes in both blood and the upper airway.

Moreover, older patients exhibited heightened innate immune responses and reduced adaptive immune responses, with increased monocyte production and decreased naïve T and B cells. This led to a persistent rise in pro-inflammatory genes and cytokines, making it harder for the body to turn off the inflammatory response. The most severe disease markers, like interleukin-6, were most pronounced in the oldest patients.

Dr. Phan concluded that aging is associated with impaired viral clearance, dysregulated immune signaling, and persistent activation of pro-inflammatory genes and proteins. These findings could pave the way for targeted treatments for older adults with severe COVID-19, potentially improving outcomes with therapies aimed at specific inflammatory cytokines.