Researchers find how immune cells prevent lung healing after viral infection

Researchers found a mechanism by which immune cells impede the regeneration of the lungs' defensive barrier following viral infections such as COVID-19.

The results of the multicenter study co-led by Cedars-Sinai, which were published in Nature, could result in novel therapeutic approaches.

The COVID-19 pandemic made clear how viral infections can have long-lasting consequences, a condition known as protracted COVID. Long COVID, sometimes referred to as post-acute sequelae of SARS-CoV-2, has caused a terrible legacy of individuals who remain incapacitated for an extended period of time following infection. Lung scarring, or post-acute sequelae of SARS-CoV-2 pulmonary fibrosis, is one such sign.

Those with long COVID can present with a broad constellation of symptoms, including post-acute sequelae of SARS-CoV-2 pulmonary fibrosis, which can cause severe difficulty breathing that requires oxygen supplementation. Patients with the most severe breathing difficulty may also need a lung transplant. Without additional treatment options, many patients are often left with long-term disability and life-threatening complications.

"This study sought to understand the pathways that led to abnormal repair in the lungs that produced a scar-forming environment," said Peter Chen, MD, co-corresponding author of the study, the Medallion Chair in Molecular Medicine and the interim chair of the Department of Medicine at Cedars-Sinai. "Our findings may lead to therapeutic strategies to prevent fibrotic lung disease after viral illnesses."

Investigators established models of post-viral lung disease and used molecular profiling and imaging to identify immune cells called CD8+ T cells as a driving factor in preventing lung healing and repair post-infection. Moreover, the investigators used post-acute sequelae of SARS-CoV-2 pulmonary fibrosis patient cohorts to validate the abnormal immunologic pathways, corroborating the animal model work.

"Although we based the work on post-acute sequelae of SARS-CoV-2 pulmonary fibrosis, other viral pandemics in the past have also revealed that ability to cause lung scarring after infection--like swine flu," said Jie Sun, PhD, co-corresponding author of the study and professor of Medicine at the University of Virginia School of Medicine. "The research and broader medical field must be prepared and better understand how to prevent adverse outcomes stemming from these viruses."

Chen and Sun say these findings--and similar studies--could provide novel information into the pathobiology of other forms of lung fibrosis.

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