Temporary Long COVID Relief Seen With Antihistamines and Anti-Inflammatories

For millions suffering from the exhausting aftermath of a COVID-19 infection, finding a reliable treatment has felt nearly impossible.

Conducted across 12 NHS specialist clinics in the UK, a new clinical trial revealed that while some repurposed drugs offer brief, minor relief, comprehensive specialist care provides the most meaningful long-term improvement for long COVID fatigue.

The search for effective treatments to tackle long COVID fatigue

Long COVID remains a serious global health challenge, affecting 1%–5% of adults worldwide. Fatigue is the most common symptom, and less than 15% of patients with persistent fatigue recover within two years. This illness imposes both a clinical and economic burden, straining healthcare resources and lowering individual quality of life.

Despite the condition’s prevalence, there is a large gap in high-quality clinical evidence. Most prior trials focused on patients who were hospitalized during their initial infection, neglecting the majority of people with long COVID who managed their illness at home.

Early, small studies of potential drugs produced inconsistent results, leaving doctors without clear treatment options.

The new STIMULATE-ICP trial investigated whether three repurposed drug classes—an anti-inflammatory (colchicine), an antihistamine combination (famotidine-loratadine), and an anticoagulant (rivaroxaban)—could reduce fatigue in non-hospitalized adults.

“Because long COVID is such a new and complex condition, when it came to designing the trial, we started by listening to what patients were telling us about their symptoms and experiences, then looking for biological signals that might explain them and treatments that might help,” explained lead author Prof. Emma Wall, the clinical research group leader at The Francise Crick Institute and professor of infectious diseases at Queen Mary University of London.

Tracking the clinical trial results of repurposed long COVID drugs

The Phase 3, multi-arm, open-label, randomized controlled adaptive platform trial involved 778 non-hospitalized adults across 12 NHS specialist long COVID clinics in the UK.

“We tested potential medicines based on the most promising theories of how to improve long COVID when we started out in 2021,” said co-author Prof. Amitava Banerjee, a professor of clinical data science at University College London.

At 12 weeks, all groups—including the no-drug group—experienced a reduction in fatigue, with an average 4.3-point improvement across the trial. Colchicine and antihistamines yielded small, additional improvements (1.49 and 1.48 points, respectively) compared with usual care, while rivaroxaban had no effect.

By week 24, after stopping the medications, these small benefits disappeared, and fatigue levels returned to usual care levels.

“Our findings suggest these drugs alone are unlikely to be the answer to long COVID fatigue. Antihistamines and the anti-inflammatory drug, colchicine, did provide a small benefit, but this did not last once participants stopped taking them and so they are unlikely to improve symptoms over the long term on their own,” said Banerjee.

Treatments were generally well-tolerated, causing only minor side effects such as mild stomach upset or slight bleeding, with no serious drug-related adverse events.

The future of long COVID healthcare

While these drugs are not a standalone cure, the temporary relief they offered provides biological clues.

“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,” said Banerjee.

Instead of relying solely on drugs, the trial highlights the power of structured medical support.

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“It is heartening that people had a significant reduction in fatigue across all arms of the trial. This is more than you would expect based on time alone, given that participants had severe fatigue at recruitment and had been ill for more than a year on average,” said co-author Dr. Melissa Heightman, the deputy clinical divisional director for medical specialities at University College London Hospitals NHS Foundation Trust.

“This level of improvement shows the importance of specialist long COVID care. These services in England offer integrated care from a range of specialties with community-based rehabilitation to develop a plan for a person based on their symptoms and all of the ways the condition affects them,” Heightman added.

The open-label design remains a limitation, as researchers cannot rule out a placebo effect. Future research must focus on double-blind trials, combination therapies, and matching specific treatments to patient subgroups.

“The National Institute for Health and Care Research (NIHR) is proud to have funded this vital trial, which highlights the value of specialist care in delivering meaningful relief for long COVID patients. Finding even modest benefits for these inexpensive drugs, which are safe and commonly used for other conditions, is incredibly important to improve the evidence-based treatment of this complex condition. By providing the high-quality data needed to refine clinical approaches, this research ensures that the NIHR is helping to build a clearer, safer path forward for patient care, which can be provided in the community,” said Prof. Danny McAuley, the scientific director for NIHR Programmes.

“The value of these results is not only that they suggest a potential treatment approach, but that they help us understand the biology of long COVID itself. Every signal we see in the trial helps us refine our understanding of the immune and inflammatory mechanisms that may be driving the disease, to develop new, better targeted treatments for future trials,” said Wall.

Reference: Wall EC, Prescott G, Dehbi HM, et al. 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. Lancet Infect Dis. 2026:S1473309926002422. doi: 10.1016/S1473-3099(26)00242-2

This article is a rework of a press release issued by University College London. Material has been edited for length and content.