Researchers have identified a mechanism through which immune cells hinder the healing process of the lungs’ protective barrier following viral infections such as COVID-19.
A team conducting a multicenter study, led in part by Cedars-Sinai, has uncovered a pathway that immune cells use to impede the healing of the lungs’ protective barrier after viral infections like COVID-19. Their findings, published in Nature, could pave the way for new treatment approaches.
The COVID-19 pandemic highlighted the long-term repercussions of viral infections, a condition referred to as long COVID. Also known as post-acute sequelae of SARS-CoV-2, long COVID has significantly impacted many individuals who suffer from enduring debilitating effects after the initial infection. One notable consequence is lung scarring, termed post-acute sequelae of SARS-CoV-2 pulmonary fibrosis.
People with long COVID may experience a range of symptoms, including post-acute sequelae of SARS-CoV-2 pulmonary fibrosis, which can lead to severe breathing difficulties that necessitate oxygen therapy. Those facing the most severe breathing challenges might require a lung transplant. Without new treatment options, many patients are often left grappling with long-term disabilities and life-threatening health issues.
“This study aimed to uncover the mechanisms leading to abnormal lung repair that creates a fibrotic environment,” explained Peter Chen, MD, co-corresponding author of the research, who holds the Medallion Chair in Molecular Medicine and serves as the interim chair of the Department of Medicine at Cedars-Sinai. “Our results could guide the development of treatments to prevent fibrotic lung conditions following viral infections.”
The research team created models of post-viral lung diseases and employed molecular profiling and imaging techniques to pinpoint CD8+ T cells as a key factor that obstructs lung healing after infection. Additionally, they analyzed patient groups suffering from post-acute sequelae of SARS-CoV-2 pulmonary fibrosis to confirm the unusual immune pathways, reinforcing the findings from animal models.
“While our study focused on post-acute sequelae of SARS-CoV-2 pulmonary fibrosis, past viral outbreaks have also shown their potential to cause lung scarring post-infection, such as swine flu,” stated Jie Sun, PhD, co-corresponding author of the study and a professor of Medicine at the University of Virginia School of Medicine. “The research community and healthcare sector must be ready and develop a deeper understanding of how to mitigate adverse effects related to these viruses.”
Chen and Sun believe that these findings—and similar investigations—could offer pioneering insights into the pathobiology of different types of lung fibrosis.
Additional authors from Cedars-Sinai include Tanyalak Parimon, Changfu Yao, and Alberto Marchesvsky. Other contributors to this study comprise Harish Narasimhan, Su Cheon, Wei Qian, Sheng’en Shawn Hu, Chaofan Li, Nick Goplen, Yue Wu, Xiaoqin We, Young Min Son, Elizabeth Fink, Gislane de Almeida Santos, Jinyi Tang, Lyndsey Muehling, Glenda Canderan, Alexandra Kadl, Abigail Cannon, Samuel Young, Riley Hannan, Grace Bingham, Mohammed Arish, Arka Sen Chaudhari, Jun sub Im, Cameron L.R. Mattingly, Patcharin Pramoonjago, Jeffrey Sturek, Jacob E. Kohlmeier, Yun Michael Shim, Judith Woodfolk, and Chongzhi Zang.
This study received partial funding from the US National Institutes of Health through grants AI147394, AG069264, AI112844, HL170961, AI176171, and AI154598 to J.S., R01HL132287, R01HL167202, and R01HL132177 to Y.M.S., R35HL150803 to J.E.K., as well as the Emory Center of Excellence for Influenza Research and Response grant 75N93019R0028 to J.E.K. Additional support was provided through F31HL164049-01A1 to C.L.R.M. and F31HL170746 and T32AI007496 to H.N.
