University of Virginia School of Medicine researchers have identified a potential treatment for the respiratory symptoms of long COVID after discovering a previously unknown cause of the condition inside the lungs.
UVA researcher Jie Sun led the team that found that COVID infection can cause sweeping changes in immune cells inside the lung tissues, promoting scarring and driving ongoing inflammation even after the initial infection has passed. This ongoing inflammation, they believe, drives the lasting respiratory symptoms, such as cough and difficulty breathing, associated with long COVID.
The new research from Sun and his colleagues indicates doctors may be able to halt the chronic inflammation using a class of drugs now used to treat rheumatoid arthritis, including baricitinib. The anti-inflammatory drugs previously received emergency authorization from the federal Food and Drug Administration to treat uncontrolled inflammation seen in severe COVID-19 infections.
"Our study identified a root cause of the respiratory complication of long COVID by performing comparative analysis of both clinical samples and a relevant animal model," said Sun, of UVA's Carter Center for Immunology Research and Division of Infectious Diseases and International Health. "We hope that the identification of the 'driving' mechanisms will help to rationally
design clinical studies repurposing those FDA-approved drugs for respiratory long COVID soon."
Millions Struggle With Long COVID
Long COVID is estimated to affect more than 60 million people globally. For these patients, a COVID-19 infection can become a prolonged ordeal, with symptoms lasting weeks, months or even years. Symptoms of long COVID can range from uncomfortable to debilitating; for example, respiratory symptoms can include shortness of breath, chest pain and even chronic lung scarring known as interstitial lung disease.
Prior research into long COVID-19 has focused on patients' blood, but Sun and his team investigated the changes occurring in the lung tissue. UVA researchers looked at cell samples collected from the lower airways of both lab mice and human patients. In both cases, they found immune cells - macrophages and T cells - had gone haywire and were having faulty, harmful interactions. These cells normally help the body fight off the disease, but, in this case, they never stopped fighting, even after the initial COVID-19 infection had passed.
The macrophages, the researchers found, flooded into the lungs in abnormal numbers and promoted tissue scarring. The T cells meanwhile, pumped out a substance called interferon that spurs continued inflammation.
UVA School of Medicine researcher Jie Sun led the team that found COVID-19 infections can change immune cells found in lung tissue. (Photo by Erin Edgerton, University Communications)
Sun and his team believe doctors may be able to break this cycle of inflammation using drugs already approved to treat the harmful inflammation seen in patients with rheumatoid arthritis, a chronic autoimmune disease that affects joints. Additional research will be needed, but Sun hopes UVA's new discoveries will lead to much-needed new treatments for patients struggling with respiratory symptoms from long COVID.
"We hope our clinical colleagues around the globe could perform clinical trials soon to test the efficacy of baricitinib or other similar drugs targeting the same inflammatory pathway in long COVID," Sun said. "Our new study has established a foundation for identification of new therapeutic interventions for long COVID by combining rigorous clinical testing and basic scientific research."
