Chronic Inflammation Unlocks Long COVID Treatment Path

A major new study from investigators at Harvard and Beth Israel Deaconess Medical Center is shedding light on the underlying biology of Long COVID (LC), a condition afflicting millions of Americans with debilitating symptoms like fatigue, brain fog, and shortness of breath. The research, published in Nature Immunology, suggests that the key difference between those who fully recover from COVID-19 and those who develop LC is persistent chronic inflammation.

For months or even years after the initial infection, patients with LC demonstrated persistent activation of chronic inflammatory pathways, immune system depletion, and disruptions in cellular metabolism, observations not seen in fully recovered patients. Utilizing a comprehensive "multi-omic" approach that integrated data on immune responses, gene expression (transcriptomics), and plasma proteins (proteomics), scientists analyzed blood samples from over 140 participants in two cohorts spanning 2020 to 2024.

The findings show that LC is characterized by chronic inflammation, T cell exhaustion, and metabolic dysregulation. Specifically, the researchers found persistent activation and upregulation of specific signaling pathways, including JAK-STAT and interleukin-6 (IL-6). These insights suggest that early, heightened inflammation during the acute phase of infection may actually set the stage for later lingering symptoms.

This discovery is crucial because most clinical trials for LC to date have focused on testing antiviral agents to clear potential residual virus, which have often shown limited efficacy. Dan H. Barouch, the study’s lead author and director of the Center for Virology and Vaccine Research at Beth Israel, emphasized that the findings define new potential therapeutic targets focused on calming chronic inflammation rather than solely clearing the virus.

The identification of these specific inflammatory pathways, such as JAK-STAT, has already led to clinical action. Barouch has initiated a clinical trial testing a JAK1 inhibitor, an anti-inflammatory drug typically used to treat eczema, which targets one of these upregulated pathways in LC patients. Experts agree that identifying the biological causes of LC is critical for developing effective treatments beyond symptomatic relief. The data strongly suggests that anti-inflammatory drugs will play a role in future therapeutic strategies.

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🔖 Sources

Long COVID involves activation of proinflammatory and immune exhaustion pathways

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Keywords: Chronic Inflammation Long COVID

Chronic Inflammation Long COVID

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