New laboratory research offers fresh insight into why coronavirus infection may lead to long COVID, while influenza often does not. In a longitudinal mouse study, researchers compared the long-term effects of coronavirus infection with those of influenza A on the lungs and brain.
Both viruses caused lasting lung inflammation weeks after infection, but the damage differed substantially. Coronavirus-infected lungs showed ongoing activation of inflammatory, clotting, and fibrotic pathways, alongside disruption of normal tissue structure and metabolism, consistent with scarring and impaired lung repair. Influenza infection, by contrast, triggered a strong early immune response followed by signs of epithelial regeneration, suggesting a more effective healing process.
Neither virus was detected directly in the brain. However, coronavirus infection led to early microvascular bleeding and sustained brain inflammation. Gene expression analysis revealed changes linked to blood vessel dysfunction, immune activation, and hormonal regulation disruption, patterns resembling long COVID symptoms like brain fog and fatigue. These changes were absent in influenza-infected mice.
The study highlights that long COVID is unlikely driven by persistent viral infection alone. Instead, ongoing immune activation, vascular injury, and impaired tissue repair appear central. The findings suggest coronavirus uniquely alters organ communication, including lung-brain interactions, long after acute infection.
These results provide a biological framework for understanding long COVID and may support the development of targeted therapies to reduce inflammation, prevent fibrosis, and protect the brain after coronavirus infection. Further clinical studies are needed to confirm these mechanisms in humans.