Arthritis medications that are already approved for use may be able to address chronic lung issues that persist for months or even years after COVID-19 infections, according to recent findings from the University of Virginia School of Medicine and Cedars-Sinai.
Recent studies indicate that existing arthritis medications might help tackle persistent lung problems that can linger for months or years following COVID-19 infections, as revealed by researchers from the University of Virginia School of Medicine and Cedars-Sinai.
The researchers studied damaged human lungs and created a new laboratory model, which helped them pinpoint dysfunctional immune processes that contribute to ongoing lung issues that many individuals experience even after they have seemingly recovered from COVID-19. These lasting effects, referred to as “post-infection lung fibrosis,” lack effective treatments. However, the findings indicate that currently available drugs such as baricitinib and anakinra could interfere with these abnormal immune responses, thereby promoting healing in damaged lungs.
“Our collaboration with doctors and computational biologists at UVA and Cedars-Sinai, including Drs. Chen and Zang, has helped us discover the underlying cause of sustained lung inflammation and scarring following severe COVID-19 infections and potentially similar respiratory infections like the flu,” remarked Jie Sun, PhD, at UVA’s Carter Center for Immunology Research and Division of Infectious Diseases and International Health. “Utilizing advanced methodologies like spatial transcriptomics and cutting-edge microscopy, we compared lung tissues from patients with those from the animal models we developed. We found that malfunctioning immune cells hinder the normal healing process in the lungs after viral damage. Crucially, we also identified the molecules involved in this issue and possible treatment options for individuals facing ongoing lung damage.”
“‘Spatial-omics’ utilizes advanced technological techniques to assess molecular characteristics with spatial context within a sample,” explained Chongzhi Zang, PhD, from UVA’s Department of Genome Sciences. “This research exemplifies the advantages of combining spatial transcriptomics with data science techniques to uncover the molecular causes of long COVID.”
The researchers believe that their discoveries could be significant not only for lung scarring resulting from COVID-19 but also for lung fibrosis from other causes.
“This study illustrates that treatments designed for acute COVID-19 may also mitigate the occurrence of chronic complications, including lung scarring,” stated Peter Chen, MD, the Medallion Chair in Molecular Medicine and acting chair of the Department of Medicine at Cedars-Sinai. “Our research will establish a foundation for developing treatments for lung fibrosis related to viral infections and other conditions.”
Grasping COVID-19 Related Lung Damage
The research team, led by Sun, Chen, and Zang, sought to gain deeper insights into the cellular and molecular mechanisms behind the persistent lung issues following COVID-19 infection. These issues can encompass lasting lung damage and harmful inflammation that continues long after the COVID-19 virus has been cleared from the body.
The researchers initiated their investigation by examining the severely damaged lungs of transplant patients at UVA and Cedars-Sinai. None of these patients had a pre-existing lung condition that warranted a transplant before contracting COVID-19, leading the scientists to hope that the lung samples would shed light on why these patients experienced such severe lung damage and ongoing fibrosis. Utilizing their findings, the scientists created a new mouse model to explore how normally beneficial immune responses might become problematic.
The findings revealed that a type of immune cell, known as CD8+ T cells, was interacting improperly with another immune cell type, macrophages. This faulty interaction resulted in the macrophages inducing harmful inflammation even after the initial COVID-19 infection had subsided, at a time when the immune system would typically relax its response.
Though the researchers are still investigating what triggers this immune dysfunction, they speculate it might be due to lingering remnants of the COVID-19 virus or another unidentified factor.
The study suggests that this vicious cycle of inflammation, damage, and fibrosis can potentially be broken using medications like baricitinib and anakinra, both of which have already received approval from the FDA for treating the harmful inflammation seen in rheumatoid arthritis and alopecia, a condition that leads to hair loss.
While further research is needed to confirm the efficacy of these drugs for this purpose, the team is hopeful that their findings will eventually provide treatment options for patients struggling with lingering lung issues post-COVID.
“Tens of millions globally are facing complications associated with long COVID and other post-infection syndromes,” stated Sun. “We are just starting to grasp the long-term health impacts caused by acute infections. There is an urgent need for more foundational, translational, and clinical research, combined with collaborative efforts across disciplines, to meet the unmet needs of these patients.”
Published Findings
The research team’s findings are published in the journal Nature. The team included researchers such as Harish Narasimhan, In Su Cheon, Wei Qian, Shengen Shawn Hu, Tanyalak Parimon, Chaofan Li, Nick Goplen, Yue Wu, Xiaoqin Wei, Young Min Son, Elizabeth Fink, Gislane de Almeida Santos, Jinyi Tang, Changfu Yao, 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, Alberto Marchesvsky, Jeffrey Sturek, Jacob E. Kohlmeier, Yun Michael Shim, Judith Woodfolk, Zang, Chen, and Sun. Sun receives unrelated research support from Icosavax, while Woodfolk gets support from Regeneron.
This research was backed by the National Institutes of Health under grants AI147394, AG069264, AI112844, HL170961, AI176171, AI154598, F31HL164049-01A1, F31HL170746, R01HL132287, R01HL167202, R01HL132177, R35HL150803, and T32AI007496; and the Emory Center of Excellence for Influenza Research and Response, grant 75N93019R0028.
