Over-the-counter antihistamines and a prescription anti-inflammatory drug both have a small benefit in reducing long Covid fatigue among people receiving care from specialist long Covid clinics, according to new findings from a large clinical trial led by UCL and UCLH.
The study, published in The Lancet Infectious Diseases journal and funded by the National Institute for Health and Care Research (NIHR), involved nearly 800 adults in England with long Covid who were randomly assigned either usual care or one of three types of drugs: a combination of antihistamines (allergy medicines), an anti-inflammatory drug called colchicine (used to treat gout), or a blood thinner called rivaroxaban (typically used to prevent blood clots and strokes).
The research team found that all groups experienced a meaningful reduction in their self-reported fatigue over 12 weeks (improving an average of 4.3 points on a 40-point scale), supporting the idea that specialist long Covid care can lead to important improvements in symptoms.
Those taking antihistamines and colchicine, but not the blood thinner rivaroxaban, saw a small additional benefit in fatigue reduction at 12 weeks (an extra 1.5 point improvement on the scale). However, this benefit was not sustained at 24 weeks (12 weeks after the participants stopped taking the drugs).
The trial was conducted by a national team of researchers, clinicians and patients across 12 clinics in England and Scotland led by co-chief investigators Professor Amitava Banerjee at UCL and Dr Melissa Heightman at UCLH. More than 30 organisations were involved, with UCLH recruiting around half the patients on this trial and the University of Lancashire Clinical Trials Unit co-ordinating all of the recruiting sites.
Professor Banerjee (UCL Institute of Health Informatics), the corresponding author, said: "We tested potential medicines based on the most promising theories of how to improve long Covid when we started out in 2021. 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.
"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.
"The blood thinner, rivaroxaban, had no benefit and so our results do not support the use of anti-coagulation medicine for long Covid."
Dr Melissa Heightman, clinical lead for the post-Covid service at UCLH, said: "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 been ill for more than a year on average.
"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."
Participants of the trial were adults with long Covid who had not been hospitalised. The 12 long Covid clinics ranged from Hull and the Highlands to Leicester and London. Fatigue was assessed with a questionnaire at the start of the trial and then after 12 and 24 weeks.
The trial was open-label, meaning participants knew which drug they were taking (there was no placebo in the non-drug group), and so the researchers were unable to rule out a placebo effect. However, they said the benefit seen in two of the drug groups was unlikely to be caused by placebo alone, given that no such benefit was found for the other drug group (rivaroxaban).
Professor Banerjee said: "We have shown it is possible to conduct a large clinical trial for long Covid and to test treatments as we would for any other condition."
Professor Danny McAuley, Scientific Director for NIHR Programmes, said: "The 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."
Professor Emma Wall, Clinical Research Group Leader at the Crick, Professor of Infectious Diseases at Queen Mary University of London, and academic consultant in Infectious Diseases and Acute Medicine for UCLH, said: "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.
"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."
