New Research Uncovers Long COVID's Lasting Impact on Brain, Lungs, and Mental Health

Two new studies shed further light on the prolonged effects of long COVID, revealing both biological damage to organs and elevated risks of mental health conditions years after initial infection. Together, the research underscores the broad and enduring toll of COVID-19 on affected individuals.

A longitudinal mouse study published in Frontiers in Immunology compared the long-term effects of coronavirus infection with those of influenza A on the lungs and brain, finding that the two viruses trigger markedly different biological responses. While both viruses caused lasting lung inflammation weeks after infection, coronavirus-infected lungs showed ongoing activation of inflammatory, clotting, and fibrotic pathways, alongside disruption of normal tissue structure and metabolism — changes consistent with scarring and impaired lung repair. Influenza infection, by contrast, triggered a strong early immune response followed by signs of epithelial regeneration and tissue healing, suggesting a more effective recovery process.

Neither virus was detected directly in the brain, yet coronavirus infection led to clear neurological effects in the mice. Infected animals developed early microvascular bleeding and sustained brain inflammation at all time points studied. Gene expression analysis revealed changes linked to blood vessel dysfunction, immune activation, and extracellular matrix remodelling. Coronavirus infection also disrupted pathways related to hormonal regulation and sensory processing in the brain, patterns that resemble neurological symptoms reported in long COVID such as brain fog and fatigue — changes that were absent in influenza-infected mice.

The researchers concluded that long COVID is unlikely to be driven by persistent viral infection alone. Instead, ongoing immune activation, vascular injury, and impaired tissue repair appear central to disease development. The findings also suggest that coronavirus uniquely alters communication between organs, including lung–brain interactions, long after acute infection. The authors noted that further clinical studies are needed to confirm whether these mechanisms operate in people with long COVID.

Meanwhile, a large population-based study published in BMC Public Health found that adults with long COVID face an increased risk of developing depressive and anxiety symptoms up to three years after their initial infection. Researchers at the University of Missouri analyzed data from Michigan adults with confirmed SARS-CoV-2 infection from March 2020 to May 2022, excluding those who reported depressive or anxiety symptoms at baseline to examine new-onset mental illness over time. Long COVID was defined as symptoms lasting 90 days or more after initial infection.

By the three-year follow-up, 16.9% of adults with long COVID reported depressive symptoms, compared with 7.5% of those without. Anxiety was reported by 17.2% of those with long COVID, versus 9.3% of those without. Overall, adults with long COVID had an 86% higher risk of depressive symptoms and a 60% higher risk of anxiety symptoms at three years. Depressive symptoms were most strongly associated with long COVID at the later follow-up, while anxiety symptoms persisted across both the 1.5-year and three-year assessments. The researchers suggested that the delayed depressive association may reflect cumulative effects of prolonged symptom burden, while the sustained anxiety association may indicate a more immediate stress-related response.

The study authors concluded that medical professionals should continue to follow up with individuals affected by long COVID to monitor their mental health, and that communities could consider implementing social support programs to promote psychological well-being among this population.