Zhao et al. (2025)
- Authors: Jingya Zhao, Yingqi Lyu, Jieming Qu.
- Institutes: Department of Pulmonary and Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
- Publisher: Frontiers in Medicine (Front. Med.), Higher Education Press.
- Link: DOI
Summary
This review of Long COVID treatments is highly relevant for the ME/CFS community, as it explores therapies for a condition with significant symptomatic overlap, including the potential for a formal ME/CFS diagnosis post-COVID. The paper systematically investigates interventions targeting key mechanisms also implicated in ME/CFS, such as immune dysfunction, neuroinflammation, microclots, and mitochondrial issues. The mention of familiar approaches like pacing and low-dose naltrexone (LDN), alongside emerging drugs like BC007 which targets autoantibodies, reinforces shared biological pathways and highlights how the massive research effort into Long COVID may accelerate therapeutic discovery for ME/CFS.
What was researched?
This article reviews and summarizes the existing evidence for a wide range of potential therapeutic strategies for Long COVID, covering both non-pharmaceutical interventions and various pharmacological treatments. The authors categorize these approaches based on the current understanding of the underlying biological mechanisms of the condition, such as viral persistence, chronic inflammation, and microclots.
Why was it researched?
Long COVID affects at least 65 million people worldwide with a wide array of debilitating symptoms, including ME/CFS, yet there are no officially approved treatments. This review was conducted to consolidate the emerging research on potential therapies and link them to the proposed biological causes of the condition. The goal is to provide a comprehensive overview to guide future research and clinical strategies.
How was it researched?
This study is a literature review, referred to as a “Comment” article. The authors analyzed and summarized findings from a wide range of existing research papers, including randomized controlled trials, case series, and pilot studies. They systematically organized the collected evidence into non-pharmaceutical and pharmaceutical interventions to provide a broad overview of the current therapeutic landscape for Long COVID.
What has been found?
The review found that a diverse range of treatments show potential for Long COVID. Non-pharmaceutical approaches like pacing and breathing exercises are beneficial, though caution with unmoderated exercise is advised. In pharmaceuticals, antivirals such as ensitrelvir 💊 and nirmatrelvir/ritonavir 💊 taken during acute infection may lower Long COVID risk. Symptom-specific drugs like low-dose naltrexone (LDN) 💊, anti-inflammatory agents like metformin 💊, and nutraceuticals including symbiotic preparations 💊 have demonstrated benefits for symptoms like fatigue and neuroinflammation. Other emerging interventions like hyperbaric oxygen therapy (HBOT) 💊 and the aptamer drug BC007 💊 have also shown positive results in early studies.
Discussion
The authors emphasize that while many potential treatments are emerging, the overall evidence is still limited and lacks high-quality, large-scale randomized controlled trials. They identify the uncertainty about the root cause of Long COVID as the primary barrier to developing effective, targeted treatments. Consequently, current strategies often require a multidisciplinary and multi-drug approach to manage the complex, multi-systemic symptoms.
Conclusion & Future Work
The authors conclude that while evidence for Long COVID treatments is in its early stages, a variety of promising interventions are being investigated. They suggest that future progress depends on a deeper understanding of the disease’s underlying mechanisms. This will enable the development of specific biomarkers and targeted drugs to guide more precise diagnosis and treatment in the future.