Aid et al. (2025)
- Authors: Malika Aid, Valentin Boero-Teyssier, Katherine McMahan, Rammy Dong, Michael Doyle, Nazim Belabbaci, Erica Borducchi, Ai-Ris Y. Collier, Janet Mullington, Dan H. Barouch
- Institutes: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA
- Publisher: Nature Immunology
- Link: DOI
Summary
This research provides a detailed biological map of Long COVID, moving the scientific understanding toward a model of persistent immune system overdrive. By identifying specific pathways like JAK-STAT, the study offers immediate targets for clinical trials and provides patients with concrete evidence of biological dysfunction. This work helps validate the physical basis of the condition and suggests a shift in treatment strategies toward immune-modulating therapies rather than just antivirals.
What was researched?
This study examined the biological mechanisms of Long COVID by investigating immune system changes, protein levels, and the presence of residual virus in patients months after their initial infection.
Why was it researched?
Researchers aimed to understand why symptoms persist in some individuals and to identify specific biological signatures that could lead to diagnostic tests or effective treatments.
How was it researched?
The team performed multi-omic analysis—combining genetic, protein, and viral data—on a cohort of 142 individuals and validated their findings in a second independent group. Participants included those with Long COVID, those who fully recovered, and uninfected controls.
What has been found?
Long COVID patients showed persistent activation of the IL-6 and JAK-STAT signaling pathways and signs of T-cell exhaustion more than 180 days after infection. While no active viral replication was detected, higher levels of inflammation during the initial acute infection were found to predict the later development of Long COVID.
Discussion
The findings suggest that Long COVID is driven by a state of chronic immune dysregulation and exhaustion rather than a lingering active virus. This suggests that treatments targeting specific inflammatory pathways, such as JAK1 inhibitors 💊 like abrocitinib, may be more effective than antiviral medications.
Conclusion & Future Work
The study identifies chronic inflammation and immune exhaustion as central drivers of Long COVID. It highlights the potential for using early immune markers to predict risk and for repurposing anti-inflammatory drugs for treatment.