Long COVID trial Over-the-counter antihistamines and the anti-inflammatory agent colchicine produced a small additional reduction in fatigue among adults with long COVID attending specialist clinics, but the benefit did not persist once treatment stopped, according to a randomised trial led by University College London (UCL) and University College London Hospitals (UCLH). Meanwhile, the anticoagulant rivaroxaban conferred no fatigue benefit.
Published in The Lancet Infectious Diseases and funded by the National Institute for Health and Care Research, the trial evaluated repurposed medicines alongside usual specialist care to identify pragmatic options for symptom relief in a condition that still lacks approved treatments.
The study enrolled nearly 800 non-hospitalised adults with long COVID across 12 clinics in England and Scotland, ranging from Hull and the Highlands to Leicester and London. Participants were randomly assigned to usual care alone or to 1 of 3 drug approaches: a combination of antihistamines, colchicine, or rivaroxaban. Fatigue was measured with a questionnaire at baseline, 12 weeks, and 24 weeks.
Across all arms, self-reported fatigue improved by an average of 4.3 points on a 40-point scale over 12 weeks. Participants receiving antihistamines or colchicine had an additional 1.5-point improvement at 12 weeks, but this advantage was no longer evident at 24 weeks — 12 weeks after stopping treatment. Rivaroxaban conferred no measurable benefit.
Amitava Banerjee, MD, UCL Institute of Health Informatics, London, said: “our findings suggest these drugs alone are unlikely to be the answer to long COVID fatigue.” Professor Banerjee added: “both antihistamines and colchicine affect the immune system and it may be that they address the immune dysregulation that long COVID has been linked to, but further research is needed to understand the possible mechanism,” and noted that the results “do not support the use of anti-coagulation medicine for long COVID.”
Melissa Heightman, MD, UCLH, London, said: “this level of improvement shows the importance of specialist long COVID care,” pointing to integrated, community-based rehabilitation as central to the gains observed across all trial arms.
The trial was open-label, with no placebo in the usual-care group, and the researchers could not fully exclude a placebo effect, although they noted that no benefit was observed in the rivaroxaban arm. Further trials are needed to clarify the underlying immune and inflammatory mechanisms and to develop better-targeted therapies.