Putrino (2025)
- Authors: David Putrino
- Institutes: The Cohen Center for Recovery from Complex Chronic Illness, Icahn School of Medicine at Mount Sinai
- Publisher: ClinicalTrials.gov
- Link: DOI
Summary
This Phase 3 clinical trial investigates whether low-dose sirolimus (rapamycin) 💊, a well-known immune-modulating drug, can effectively treat the underlying biological drivers of Long COVID. By targeting the mTOR pathway, researchers aim to address cellular dysfunction and immune exhaustion that may cause persistent fatigue and cognitive issues. If the trial is successful, it could provide one of the first evidence-based pharmacological treatments for Post-Acute Sequelae of COVID-19.
What was researched?
This study evaluates the efficacy and safety of low-dose sirolimus (also known as rapamycin) for adults suffering from Long COVID. The research specifically focuses on whether the intervention improves patient-reported health outcomes and symptom severity.
Why was it researched?
The trial was initiated based on evidence that Long COVID may be driven by mTOR pathway overactivation, mitochondrial dysfunction, and viral persistence. Researchers believe that inhibiting this pathway could potentially reset the immune system and improve energy production at a cellular level.
How was it researched?
This is an IND-exempt, randomized, double-blind, placebo-controlled clinical trial involving approximately 80 participants. The study utilizes a multi-ascending dose escalation scheme over a 12-week treatment period to identify the most effective and tolerable dosage for patients.
What has been found?
As the trial is currently in the recruitment phase, definitive efficacy results have not yet been published. Preliminary observations from other cohorts indicated that patients taking sirolimus for unrelated reasons appeared to have a lower incidence of developing Long COVID after a SARS-CoV-2 infection.
Discussion
A key strength of this study is its focus on Post-Exertional Malaise (PEM) and moderate-to-severe fatigue as inclusion criteria. However, the exclusion of individuals with pre-2020 ME/CFS diagnoses limits the immediate generalizability to the broader chronic fatigue community.
Conclusion & Future Work
The trial represents a significant effort to repurpose existing medications to treat complex post-viral conditions. Future results will determine if mTOR inhibition is a viable therapeutic target for PASC and similar chronic illnesses.