Rheumatoid Arthritis Drug May Halt Long COVID Inflammation

Researchers from the University of Virginia School of Medicine have identified a previously unknown cause of long COVID within the lungs. Their study, published in Science Translational Medicine, suggests that a treatment previously used for rheumatoid arthritis might be effective in halting the chronic inflammation associated with the condition.

No one-size-fits-all treatment for long COVID

Post-COVID-19 Syndrome, also known as long COVID, affects around 65 million people worldwide. The condition is characterized by fatigue, shortness of breath, chest pain and cognitive dysfunction or “brain fog”. Symptoms can last from weeks to months and even years, ranging from mild discomfort to debilitating pain that can impact daily functioning.

Although there are leading theories on the cause of long COVID, researchers are still yet to determine why the chronic condition persists in some individuals but not others. There is no one-size-fits-all medication for treating long COVID; instead, current treatments concentrate on managing the array of symptoms experienced by patients.

Previous research has focused on understanding the cause(s) of the condition via analysis of a patient’s blood samples, rather than investigating the immune status within affected organ tissue. Although animal models have been used for such investigation, it is unclear whether these accurately model the human pathogen, thus calling for a comprehensive comparative analysis of human clinical and animal samples.

Long COVID causes abnormal interactions between immune cells

The researchers analyzed single-cell RNA-sequencing data from samples collected from the lower airways of both human patients with and without long COVID and animal models infected with SARS-CoV-2. Analysis of the data revealed large alterations in immune cells inside the lung tissue in both models.

Further, abnormal interactions were observed between macrophages and T cells. Normally, these immune cells help the body fight against infections, however, in both human and animal samples, the immune cells were still active even after the initial infection had passed.

An increased number of macrophages were found in the lung tissue, promoting tissue scarring and chronic inflammation. Additionally, T cells were identified as driving the production of Interferon-γ (IFN-γ), a cytokine that plays an important role in inducing and modulating an array of immune responses. IFN-γ emerged as a key player in the immune cell anomalies observed in the long COVID samples.

Halting the chronic inflammation

A class of anti-inflammatory drugs, including baricitinib, have previously received emergency authorization from the federal Food and Drug Administration (FDA) to treat the uncontrolled inflammation associated with severe COVID-19 infections. Ongoing research indicates the class of drugs, traditionally used to treat chronic inflammation caused by rheumatoid arthritis, could be repurposed to treat long COVID.

“We hope that the identification of the ‘driving’ mechanisms will help to rationally design clinical studies repurposing the FDA-approved drugs for respiratory long COVID soon,” said corresponding author Dr. Jie Sun, a professor of medicine at the University of Virginia School of Medicine.

“We hope our clinical colleagues around the globe can soon perform clinical trials to test the efficacy of baricitinib or similar drugs targeting the same inflammatory pathway in long COVID,” said Sun.

“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,” said Sun.

Reference: Li C, Qian W, Wei X, et al. Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae after acute COVID-19. Sci Transl Med. 2024;16(756):eadn0136. doi: 10.1126/scitranslmed.adn0136

This article is a rework of a press release issued by the University of Virginia Health System.  Material has been edited for length and content.