Long COVID is estimated to affect more than 60 million people worldwide, who experience symptoms for weeks, months, or even years after infection with the SARS-CoV-2 coronavirus. The severity of symptoms of long COVID can range from simple discomfort to disruptions that interfere with daily life; for example, respiratory symptoms can include shortness of breath, chest pain, and even chronic lung scarring known as interstitial lung disease.
Researchers at the University of Virginia School of Medicine have now identified a potential treatment for the respiratory symptoms of long COVID after uncovering an unknown cause of the condition within the lungs. UVA researchers, led by Jie Sun, found that COVID-19 can cause radical changes in immune cells in lung tissues, promoting scarring and triggering ongoing inflammation, even after the initial infection is over. They believe this ongoing inflammation leads to the long-lasting respiratory symptoms, such as coughing and shortness of breath, associated with long COVID.
New research by Sun and colleagues suggests that doctors can stop this chronic inflammation by employing a class of drugs, including baricitinib, that are already used to treat rheumatoid arthritis. The anti-inflammatory drugs previously received emergency authorization from the Food and Drug Administration (FDA) to treat the uncontrolled inflammation seen in severe COVID-19 infections.
Causes and treatment of respiratory symptoms of long-term COVID
“Our study identified a root cause of respiratory complication from long COVID by performing comparative analyses of clinical samples and a relevant animal model,” said Sun, of UVA’s Carter Center for Immunology Research and UVA’s Division of Infectious Diseases and International Health. “We hope that identifying the ‘driving’ mechanisms will help rationally design clinical studies to soon repurpose those FDA-approved drugs for respiratory long COVID.”
Previous research into long COVID had looked for answers in patients’ blood, but Sun and his team wanted to determine what changes were happening in the lung tissues themselves, looking at cell samples collected from the lower airways of both laboratory mice and human patients.
In both cases, they found that immune cells known as macrophages and T cells had gone haywire, displaying faulty functions and harmful interactions. These cells normally help the body fight off disease, but in this case, they never stopped fighting, even after the initial COVID infection ended.
“Our study has laid the groundwork for identifying new therapeutic interventions for long COVID”
The researchers found that macrophages had flooded the lungs in abnormal numbers and were promoting tissue healing. Meanwhile, T cells were pumping out a substance called interferon that stimulates ongoing inflammation. Their findings have been published in Science Translational Medicine.
Sun and his team believe that doctors can break this cycle of inflammation by using drugs that are already approved to treat the inflammation that characterizes rheumatoid arthritis, a chronic autoimmune disease that affects the joints. While further research is needed, Sun hopes that their findings will lead to new effective treatments for the respiratory symptoms of long COVID.
“We hope that our clinical colleagues around the world will soon be able to conduct clinical trials to test the efficacy of baricitinib or other similar drugs targeting the same inflammatory pathway in long COVID,” Sun said. “Our new study has laid the groundwork for identifying new therapeutic interventions for long COVID by combining rigorous clinical testing and basic science research.”
