Scientists discover key to long COVID lung damage and potential treatment

Researchers at the University of Virginia (UVA) School of Medicine have made a significant breakthrough in understanding the prolonged effects of long COVID. Their study reveals how severe COVID-19 infections interfere with immune cells’ ability to repair lung tissue. These findings not only shed light on long COVID’s persistent symptoms but also suggest a potential new treatment approach for both short-term and chronic respiratory infections, including the flu.

Led by Dr Jie Sun, the research discovered that severe viral infections such as COVID-19 and influenza cause significant damage to a key organelle within immune cells called peroxisomes. These organelles, found in macrophages – the immune cells responsible for directing lung repair – are vital for resolving inflammation and healing damaged lung tissue. When peroxisomes degrade due to severe infection, they lose their ability to function properly, leading to prolonged lung inflammation and scarring.

A potential treatment breakthrough

Encouragingly, the UVA researchers found that they could enhance peroxisome function and restore the immune system’s ability to heal the lungs using a drug already approved by the US Food and Drug Administration (FDA). Sodium phenylbutyrate, currently used to treat high levels of ammonia in the blood, showed promising results in early testing for reversing peroxisome impairment in both lab mice and human patients who had suffered from severe COVID-19.

“COVID-19 can leave the lungs unable to heal properly by damaging these tiny structures inside our cells,” said Sun, a researcher at UVA’s Carter Centre for Immunology Research and UVA’s Division of Infectious Diseases and International Health.

“Our discovery is important because it not only explains why some people continue to have breathing problems long after their initial illness but also points us toward a potential treatment to help them recover by targeting a tiny organelle inside critical immune cells.” Sun continued, “A tiny organelle can have big roles! I hope our work could lead to new peroxisome-centric therapies that can help people suffering from long COVID.”

Understanding peroxisomes and their role in lung health

Peroxisomes, often overlooked in scientific research, play a crucial role in breaking down toxins and fats within cells. UVA’s research suggests that these organelles are also critical to resolving inflammation after severe viral lung infections. This newfound understanding opens doors to potential treatments for both acute and chronic respiratory conditions that follow infections like COVID-19 and influenza.

In their recently published study in the journal Science, Sun and his colleagues report that severe COVID-19 infections lead to drastic alterations in peroxisomes inside macrophages, severely impeding their ability to regenerate and function. The resulting loss contributes to prolonged lung inflammation and scarring. Their findings were consistent across both laboratory mice and human patients.

Peroxisomes, tiny but powerful organelles inside immune cells, play a crucial role in lung repair by reducing inflammation and supporting tissue healing after severe viral infections like COVID-19.

Implications for long COVID and other lung diseases

While further research is needed before sodium phenylbutyrate can be formally recommended for long COVID treatment, these findings highlight peroxisomes as a potential target for treating a variety of post-infection lung conditions. 

Sun said: “We are collaborating with scientists and physicians at UVA and other institutions to understand the exact function of this understudied organelle in long COVID and other chronic lung diseases such as interstitial lung disease [ILD].”

Sun emphasised the long-term goals of the research, stating, “Ultimately, we want to develop peroxisome-targeting therapies to give patients the chance to breathe more easily again and get back to their normal lives. We hope that by targeting peroxisomes, we can develop effective therapies that help patients breathe more easily and return to their normal lives.”

Funding and future directions

The research was supported by the National Institutes of Health (NIH) through multiple grants. UVA has also filed a patent application for the concept of targeting peroxisomes to treat acute and chronic conditions resulting from viral lung injuries. 

This study was published in Science.