Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review.
Yong, Shin Jie, Halim, Alice, Halim, Michael et al. · Expert opinion on investigational drugs · 2023 · DOI
Quick Summary
Researchers reviewed drug treatments being tested for long-COVID in clinical trials to see which ones might actually work. They found that most experimental drugs don't look very promising, but a few stand out: rintatolimod appears most helpful for people with ME/CFS symptoms, while other drugs like LTY-100 and Treamid might help with lung problems from long-COVID. Currently, there is no proven treatment for long-COVID, so finding effective options is urgent.
Why It Matters
This review is crucial for ME/CFS patients because it identifies which experimental drugs currently in trials might actually be effective, providing evidence-based hope during a period when no standard treatments exist. For researchers, it synthesizes the global landscape of long-COVID drug development and highlights critical gaps, informing future research priorities and funding decisions. The identification of rintatolimod as the most promising candidate for ME/CFS-like symptoms is particularly significant given the overlap between these conditions.
Observed Findings
Four completed RCTs and 22 ongoing RCTs were identified investigating 22 unique experimental drugs for long-COVID
Most investigated drugs were judged to have low potential for treating long-COVID based on three pre-specified evaluation domains
Rintatolimod emerged as having the highest potential specifically for the ME/CFS subtype of long-COVID
LTY-100 and Treamid showed promise for the pulmonary fibrosis subtype
Metformin was identified as a candidate for general long-COVID prevention rather than treatment
Inferred Conclusions
Long-COVID's heterogeneous presentation suggests that one-size-fits-all treatments are unlikely to succeed and personalized, subtype-specific approaches are necessary
Rintatolimod warrants prioritized clinical evaluation for ME/CFS-like presentations within the long-COVID spectrum
The current drug development pipeline is relatively immature, with most candidates showing insufficient promise, indicating need for better-informed drug selection strategies
Lack of funding for post-acute infection syndromes historically hindered research, though recent increased investment is beginning to yield more clinical trials
Remaining Questions
Which specific biomarkers or clinical characteristics best identify long-COVID subtypes, and how should patients be stratified for subtype-specific treatments?
What This Study Does Not Prove
This systematic review does not prove that any of these drugs are effective—it only evaluates the potential and design of trials, not actual patient outcomes. The findings are preliminary and based on pre-clinical data and early-stage trials rather than large completed studies with confirmed efficacy. The review also cannot establish which subtypes of long-COVID are most common or how to best match patients to specific treatments.