mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS.
Bar-Tana, Jacob · Journal of translational medicine · 2025 · DOI
Quick Summary
This study proposes that ME/CFS, Long COVID, and similar post-infection illnesses may all be caused by the same underlying problem: excessive activity of a cellular control system called mTORC1. The authors suggest that if this overactive system is the shared driver of these conditions, it could explain why patients experience fatigue, worsening after exercise, pain, heart rate changes, and brain fog—and it might point toward new treatments.
Why It Matters
For ME/CFS patients, identifying a shared molecular driver (if validated) could transform understanding of disease mechanisms and unlock targeted therapeutic approaches currently unavailable. This framework potentially connects post-infection illnesses that have lacked coherent biological explanation, offering hope for treatments beyond symptom management. For researchers, this hypothesis provides a testable model to investigate commonalities across conditions that clinically resemble each other but have been studied separately.
Observed Findings
Multiple post-acute infectious syndromes (PASC, ME/CFS, PAIS) share overlapping clinical features including post-exertional malaise, autonomic dysfunction, neuropsychiatric symptoms, and chronic fatigue.
mTORC1 hyperactivation is implicated in metabolic syndrome, chronic obstructive pulmonary disease, neurodegeneration, and other chronic diseases with clinical overlap to post-infection syndromes.
Common risk factors and progression patterns exist across PASC, ME/CFS, and PAIS, suggesting shared underlying biology.
Inferred Conclusions
Sustained mTORC1 hyperactivation may represent a unifying pathophysiological mechanism explaining shared features across post-acute infectious syndromes.
If validated, mTORC1-directed therapies could offer a novel treatment approach for currently therapeutically-intractable conditions.
Identifying mTORC1 pathway dysregulation could address the unmet need for mechanistic biomarkers in PASC, ME/CFS, and PAIS.
Remaining Questions
Is mTORC1 hyperactivation demonstrably present in patient tissues/cells from ME/CFS and PASC cohorts, and does its severity correlate with symptom burden?
Do specific triggers (viral pathogen, genetic predisposition, immune response) initiate or sustain mTORC1 dysregulation in post-infection syndromes?
Would mTORC1 inhibitors (e.g., rapamycin, mTORC1-selective agents) be safe and efficacious in clinical trials for these patient populations?
What This Study Does Not Prove
This study does not prove that mTORC1 hyperactivation actually causes ME/CFS or Long COVID—it is a hypothesis based on literature synthesis, not experimental evidence from patient tissues or validated biomarkers. The paper does not demonstrate that targeting mTORC1 will treat these conditions, nor does it establish that mTORC1 dysregulation is the primary driver rather than a secondary consequence of post-infectious pathology. Direct mechanistic studies in patient populations are needed to test these claims.