IN a new study researchers have identified distinct immune system pathways that may determine the severity of long-term lung damage following COVID-19. This breakthrough offers insight into why some individuals experience persistent breathing difficulties while others recover more fully.
The study focused on patients with restrictive lung disease following COVID-19 and examined hundreds of molecular and cellular immune features. Two distinct forms of lung restriction were identified, one with milder symptoms and less fibrosis, and another with more severe diffusion impairment and fibrotic changes. These differences were not only structural but also reflected in divergent immune signatures.
Using machine learning, the team found that patients with milder disease showed increases in CCR5+CD95+CD8+ T cells, suggesting a more active immune involvement. In contrast, those with more severe lung damage had reduced T cell responses and elevated CXCL13 levels, a chemokine associated with immune dysregulation. Each group displayed unique sets of immune cells, inflammatory mediators, and autoantibodies.
Importantly, these immune profiles were distinct from individuals without post-COVID lung disease, underscoring the role of type 1 T cell-driven networks in driving either ongoing injury or progression to fibrosis. These findings not only clarify the immunological basis of post-COVID respiratory complications but also point to potential therapeutic targets to mitigate long-term lung dysfunction.
Reference:
Canderan G et al. Distinct type 1 immune networks underlie the severity of restrictive lung disease after COVID-19. Nat Immunol. 2025;26:595-606.
