Arthritis medications could reverse COVID lung damage.

Arthritis drugs already available on prescription could help relieve lung issues that linger after COVID-19 infections, according to new research conducted at Cedars-Sinai and University of Virginia School of Medicine.

Through careful observation of damaged human lungs and developing an innovative new lab model, scientists were able to pinpoint malfunctioning immune processes responsible for continuing lung issues among COVID-19 survivors even after recovering otherwise from infection; known as post-infection lung fibrosis; with no definitive treatments currently available. New research, however, indicates that existing medications like baricitinib and anakinra could disrupt any malfunctioning immune response systems and finally enable damaged lungs to heal over time.

Collaboration among UVA and Cedars-Sinai doctors and computer biologists such as Drs. Chen and Zang allowed us to uncover the root causes of persistent lung inflammation and scarring after acute COVID-19 infections and potentially other respiratory infections like influenza.”
Jie Sun, Professor in the School of Medicine at University of Virginia

Utilizing cutting-edge technologies like spatial transcriptomics and sophisticated microscopy, we compared lung tissue from patients and animal models we developed in our lab to find that malfunctioning immune cells disrupt proper healing after viral damage in both. Importantly, we identified potential molecules responsible for this issue which provide potential treatment solutions for ongoing lung damage.”

“Spatial-omics technologies represent state-of-the-arts methods that use spatial location information within samples to measure molecular features with spatial location information,” explained researcher Chongzhi Zang of UVA’s Department of Genome Sciences. This work illustrates the ability of spatial transcriptomics combined with data science approaches in uncovering molecular causes behind COVID longterm sequelae.

Researchers point out that their findings could prove helpful not just in cases involving COVID but for all sources of lung fibrosis as well.

“This study shows that therapies designed to treat COVID-19 disease may also decrease its long-term sequelae, including lung scarring,” stated Peter Chen, MD, Medallion Chair in Molecular Medicine and interim Chair of Cedars-Sinai Department of Medicine. Our work will lay the groundwork for developing therapies against viral-associated lung fibrosis or other conditions causing lung fibrosis.

Understanding COVID-19 lung damage

Researchers led by Sun, Chen, and Zang sought to understand the cellular and molecular causes behind ongoing lung damage caused by COVID-19 virus infections even after its presence has been cleared from their bodies. Such complications may include chronic inflammation and ongoing damage that remains after clearance has occurred.

Researchers began by examining severely damaged transplant patient lungs at both UVA and Cedars-Sinai transplant hospitals, none of whom required transplant prior to contracting COVID-19. Hoping that their examination could yield vital insight as to why such severe lung damage and persistent fibrosis had taken place in these individuals, using this knowledge they created a mouse model designed to better understand why otherwise beneficial immune responses had gone haywire.

Researchers discovered that immune cells known as CD8+ T cells were engaging in uncharacteristically bad interactions with macrophages – leading them to cause destructive inflammation even after COVID-19 infection had subsided and when immunity should have abated.

Scientists remain uncertain as to the cause of immune malfunction in this case; possibly their bodies could still be responding to remaining remnants of COVID-19 virus; there could also be another factor at work, they assert.

Research by Baricitinib and Anakinra may offer solutions to break this dangerous cycle of inflammation, injury and fibrosis, both already approved by FDA to treat symptoms associated with Rheumatoid Arthritis or Alopecia; anakkinra was recently added.

Though more research will need to be completed to verify their efficacy for this new purpose, researchers hope their discoveries can offer patients struggling post-COVID lung problems access to much-needed treatments options.

“Tens of millions of people globally are living with complications caused by chronic COVID or post-infection syndromes, including HIV,” Sun said. “We’re only just starting to comprehend their long-term ramifications. Further basic, translational, clinical research along with multi-disciplinary collaboration is urgently required in order to meet patients’ unmet needs.”
Journal References for this Research Paper include Narasimhan H et al (2024). An aberrant immune-epithelial progenitor niche drives viral lung sequelae: Evidence from experimental models. Nature. doi.org/10.1038/s41586-024-047926-8