Which anti-inflammatory drugs have shown benefit for long COVID symptoms in clinical trials?
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Executive summary
Clinical trials reported so far have tested multiple anti‑inflammatory approaches for long COVID but have produced mixed results: a randomized trial of colchicine showed no benefit (JAMA Internal Medicine trial reported by the ME Association) [1]. Ongoing and planned trials target JAK‑STAT inhibitors such as abrocitinib and other anti‑inflammatory agents [2] [3], while several reviews and trial listings note candidates including JAK inhibitors, IL‑1 blockers (anakinra), TNF inhibitors (infliximab), and repurposed drugs with anti‑inflammatory properties are under investigation [4] [5] [6].
1. Colchicine’s clear trial result: a negative finding that matters
The strongest direct clinical‑trial evidence in the sources is a randomized trial of colchicine for long COVID that failed to show benefit; the ME Association summarizes a JAMA Internal Medicine paper reporting no therapeutic effect on functional outcomes at 12, 26 and 52 weeks in participants selected for functional limitation or elevated inflammation markers [1]. That negative result establishes that not all anti‑inflammatory drugs will work for long COVID and underlines the need for rigorous randomized trials rather than extrapolation from acute‑COVID or other inflammatory diseases [1].
2. JAK‑STAT inhibition: an active hypothesis now in trials
Researchers have identified chronic activation of the JAK‑STAT inflammatory pathway in some long COVID cohorts, and that finding has prompted trials of JAK inhibitors. Beth Israel Deaconess started a trial of abrocitinib—a JAK‑STAT pathway inhibitor already used for eczema—based on pathway activation seen in blood studies [2]. Media reporting highlights this as a prominent strategy because approved drugs exist that can be repurposed quickly [2].
3. Broader anti‑inflammatory repertoire under study
Beyond colchicine and JAK inhibitors, investigators and reviews list a range of immunomodulators and anti‑inflammatories being tested or proposed: anakinra (an IL‑1 receptor antagonist), infliximab (a TNF inhibitor), fluvoxamine (an SSRI with reported anti‑inflammatory effects), and other supplements or adjuncts like omega‑3s and CoQ10 in supportive research [5] [6]. Trial networks and consortia have planned or launched global studies to evaluate two anti‑inflammatory medicines across multiple continents, reflecting a broad strategy to test different mechanisms [3].
4. Why mixed results and heterogeneity are expected
Experts emphasize that long COVID is biologically heterogeneous—possibly multiple distinct disease trajectories—so a drug that helps one subgroup may not help others [7]. The absence of validated biomarkers for long COVID complicates interpretation of patient‑reported outcomes and trial endpoints; Medscape notes that without biomarkers it’s hard to know whether anti‑inflammatory or antiviral strategies are truly altering disease biology [4]. That background explains why trials can produce conflicting or null results even when a biological rationale exists.
5. Antivirals versus anti‑inflammatories — competing theories drive trial choices
Some researchers have pursued antivirals (e.g., Paxlovid) based on viral persistence theories, but early small studies reportedly showed no efficacy while longer regimens produced different signals in other work; reporting cautions that optimal dose/duration might matter [2] [4]. The chronic‑inflammation camp—cited in the Boston Globe—argues that targeting persistent immune activation (e.g., with JAK inhibitors) may be more promising for many patients [2]. Both approaches are being trialed in parallel, reflecting competing mechanistic hypotheses [2] [4].
6. Ongoing trials, repurposing and the regulatory landscape
Multiple repurposing efforts are underway: academic groups and consortia are running digital and global trials to test approved drugs with anti‑inflammatory effects (e.g., tirzepatide is being tested for anti‑inflammatory effects in a Scripps Study, although it is not an anti‑inflammatory per se) and SILC‑backed trials aim to accelerate evidence generation [8] [3]. No anti‑inflammatory drug has regulatory approval specifically for long COVID as of these reports; Scripps explicitly states there are currently no FDA‑approved drugs for long COVID [8].
7. What the evidence does — and does not — say now
Available sources show at least one high‑quality trial (colchicine) reporting no benefit [1], and several other agents are in active testing because of plausible biology (JAK inhibitors like abrocitinib, anakinra, infliximab, fluvoxamine) or because trial networks prioritized repurposing [2] [5] [4] [3]. Sources do not mention successful, definitive positive phase‑3 trials leading to approval of an anti‑inflammatory for long COVID; therefore claims of an established anti‑inflammatory cure are unsupported by the cited reporting [1] [8].
Limitations: reporting varies in detail and some items are press summaries rather than primary trial manuscripts; many trials are ongoing and outcomes not yet published [3] [2]. Readers should expect evolving results as large, better‑phenotyped randomized trials report.