Common Medications Show Modest Short-Term Benefit for Long COVID Fatigue, Suggests Study
USA: A large randomized clinical trial published in The Lancet Infectious Diseases found that colchicine and an inexpensive, widely available antihistamine combination (famotidine–loratadine) produced small but significant short-term reductions in fatigue among people with long COVID receiving specialist care. The benefit was seen after 12 weeks of treatment but disappeared 12 weeks after the drugs were stopped. In contrast, the blood thinner rivaroxaban showed no benefit, providing no support for routine anticoagulation to treat long COVID-related fatigue.
The findings suggest these low-cost drugs may offer temporary symptom relief, although they are not a cure, and further research is needed to identify more effective long-term treatments.
Post-COVID-19 condition, commonly known as long COVID, affects an estimated 1–5% of adults worldwide, with persistent fatigue being one of its most common and disabling symptoms. Despite the growing burden of the condition, no evidence-based drug therapy has yet been established to manage fatigue effectively.
To address this gap, researchers from the STIMULATE-ICP consortium conducted a phase 3, multicentre, open-label, randomized controlled trial across 12 UK National Health Service (NHS) long COVID clinics. The study evaluated whether three repurposed medications—colchicine, rivaroxaban, and a combination of famotidine with loratadine—could reduce fatigue when added to specialist long COVID care.
The trial enrolled 778 adults with long COVID who had not been hospitalized during their acute COVID-19 illness. Participants were randomly assigned to receive colchicine (500 µg twice daily), rivaroxaban (10 mg once daily), famotidine (40 mg) plus loratadine (10 mg) once daily, or no additional drug for 12 weeks, alongside standard specialist care. Fatigue was assessed using the Fatigue Assessment Scale (FAS), where higher scores indicate more severe fatigue.
Key findings from the study include:
- Fatigue improved across all treatment groups, including participants receiving usual care without any study drug.
- Compared with no-drug treatment, colchicine produced a small but statistically significant additional reduction in fatigue scores after 12 weeks.
- A similar modest improvement was observed with the famotidine–loratadine combination.
- Rivaroxaban did not significantly improve fatigue compared with usual care.
- By 24 weeks—12 weeks after treatment had ended—fatigue scores were no longer significantly different between the groups, indicating that the benefits were not maintained after stopping therapy.
- All three treatment strategies were generally well tolerated, with serious adverse events being uncommon and unrelated to the study medications.
Participants had severe fatigue at baseline, with a mean Fatigue Assessment Scale (FAS) score of 36.8. Fatigue improved over 12 weeks across all groups, including those receiving usual care alone, but colchicine and the famotidine–loratadine combination provided a small additional benefit during treatment.
The researchers concluded that while these low-cost repurposed drugs may offer temporary relief from long COVID fatigue, they are unlikely to provide sustained benefit on their own. They called for further research to identify patients most likely to benefit, assess combination therapies, and develop treatments that offer longer-lasting symptom improvement.
Reference:
(2026). Efficacy and safety of rivaroxaban, colchicine, and famotidine–loratadine with specialist supportive clinical care for fatigue in patients with post-COVID-19 condition in the UK: A multisite, open-label, randomised controlled trial. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(26)00242-2
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