Two inexpensive, widely available medications provided modest short-term relief from fatigue in people with long COVID, according to a large clinical trial published this week in The Lancet Infectious Diseases. 

For the study, researchers led by a team at University College London (UCL) enrolled nearly 800 adults who were receiving care at specialized long-COVID clinics in England and randomly assigned them their usual care or treatment with one of three drugs:

• colchicine, an anti-inflammatory drug commonly used to treat gout
• a combination of two antihistamines, famotidine and loratadine
• the blood thinner rivaroxaban

The researchers tracked participants’ responses to the drugs over the course of 12 weeks. None of the participants were hospitalized during the acute infection phase.

Long COVID affects an estimated 1% to 5% of adults worldwide. People with long COVID experience a range of symptoms, including fatigue, muscle pain, brain fog, and shortness of breath. There are no licensed treatments for the condition.

Fatigue improved across all groups

At the start of the trial, all participants reported severe fatigue. Together, they scored an average of 36.8 on the Fatigue Assessment Scale, a 50-point questionnaire that measures fatigue with scores ranging from 10 (no fatigue) to 50 (debilitating fatigue). A change in score of 10% or more is considered clinically significant. 

Over the course of 12 weeks, fatigue improved across all groups, including the group that received no drug intervention. On average, fatigue scores fell by 4.3 points, a clinically meaningful improvement.

The researchers also found small additional reductions in fatigue among participants taking colchicine (–1.49 points) and famotidine-loratadine (–1·48 points) compared with those receiving usual care alone. Rivaroxaban did not significantly improve fatigue.

Improvements didn’t last

But the improvements did not last. By 24 weeks, fatigue scores were no longer significantly different from those of participants who received usual care alone.

In an accompanying commentary, Tiffany Walker, MD, an associate professor in the Department of Medicine at Emory University who was not involved in the study, said the trial helps address a healthcare gap in long-COVID care. The findings support previous studies showing the benefits of antihistamines on improving long-COVID symptoms, but conflicts with previous research that reported no improvement in symptoms when taking colchicine. 

“These outcomes do not support widespread use of these medications in long COVID management,” writes Walker. “However, the study builds on the growing evidence base for potential treatments that can be implemented by long COVID care teams.”

The study builds on the growing evidence base for potential treatments that can be implemented by long COVID care teams.

The researchers came to a similar conclusion. “We tested potential medicines based on the most promising theories of how to improve long Covid when we started out in 2021,” study author and professor of clinical data science at UCL, Amitava Banerjee, PhD, says in a UCL news release.  “Our findings suggest these drugs alone are unlikely to be the answer to long Covid fatigue…They are unlikely to improve symptoms over the long term on their own.”

At the same time, he says: “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.”