Research published in the journal Nature Immunology has shed light on the mechanisms behind long COVID, a condition that affects over 400 million individuals globally. The findings indicate that chronic inflammation may play a significant role in the prolonged physical and mental effects experienced by some recovering from COVID-19.
The study, conducted at the Yale School of Medicine, analyzed brain tissue sections from mice infected with the coronavirus. It aimed to understand why certain individuals suffer from lingering symptoms long after their initial infection. The research found that patients with long COVID exhibited heightened inflammatory responses for over six months post-infection, contrasting sharply with those who fully recovered.
According to Dan Barouch, the study’s lead author and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, these findings suggest potential therapeutic targets related to inflammation that warrant further clinical exploration. “This leads to a hypothesis that there might be therapeutic targets related to inflammation that might be worth exploring in clinical studies,” Barouch stated.
Many early theories posited that long COVID symptoms persisted due to the virus itself lingering in the body. However, this latest research challenges that notion by highlighting the role of the immune system’s activation and chronic inflammation. Notably, clinical epidemiologist Ziyad Al-Aly from Washington University in St. Louis emphasized the significance of exploring these new pathways, stating, “It’s eye-opening in the sense that it gives us more information that these pathways seem to be upregulated or activated in people with long COVID.”
Long COVID can affect anyone, regardless of age or the severity of their initial symptoms. The World Health Organization has identified as many as 200 different symptoms associated with the condition, ranging from brain fog and fatigue to gastrointestinal issues and heart palpitations. These symptoms may persist for weeks, months, or even years after the initial SARS-CoV-2 infection.
The research involved two cohorts: one studied during the early pandemic years from 2020 to 2021 and another from 2023 to 2024. A total of 180 participants were analyzed, including healthy individuals, those who recovered from COVID-19, and patients suffering from long COVID. Researchers assessed protein levels, gene expression, immune responses, and viral measurements to identify differences between the groups.
Barouch noted that the study’s findings suggest that the initial COVID infection may trigger chronic inflammation, which is likely one of several factors contributing to long COVID. While the study was limited due to its small sample size, Barouch expressed optimism about the potential for larger, more diverse studies in the future.
Based on the research, Barouch has initiated a clinical trial testing an anti-inflammatory drug typically used for eczema. This trial, which is ongoing and has enrolled 45 participants, seeks to evaluate the efficacy of targeting inflammation pathways in treating long COVID. In contrast, a previous randomized trial involving a gout medication aimed at reducing inflammation showed no beneficial effects for long COVID patients.
Barouch emphasized the need for further research to determine whether targeting a single inflammatory pathway is sufficient for treatment, given the complexity of the condition. “I do think that in the broader sense, identification of chronic inflammation as associated with long COVID will lead to therapeutic strategies that include anti-inflammatory drugs,” he remarked.
Understanding the biological underpinnings of long COVID is essential for developing effective treatments. While some studies have explored the antiviral Paxlovid for long COVID, initial findings have not demonstrated efficacy. Barouch reiterated that his research complements existing theories rather than contradicting them, providing valuable data for future investigations into alternative therapies.
Rehabilitation physician Alba Azola, co-director of the Long COVID/Chronic Fatigue Syndrome Clinic at Johns Hopkins Medicine, welcomed the research as a positive shift toward exploring various treatment options. “For too long in the field of long COVID, a lot of attention has gone to viral persistence and viral-specific kind of interventions,” Azola noted. She added that identifying specific biologics targeting common pathways could enhance treatment strategies for the diverse symptoms associated with long COVID.
As research continues to evolve, the hope remains that a deeper understanding of chronic inflammation could lead to effective therapies that alleviate the suffering of millions affected by this complex condition.
