People with long COVID reported better functioning and fewer symptoms after taking low-dose naltrexone in a small retrospective study presented at the IDWeek annual meeting. The findings add to a thin treatment landscape for a condition that still has no FDA-approved therapy.
The analysis followed 230 adults whose electronic health records came from the Stanford Long COVID Clinic between 2023 and December 2025. They had laboratory-confirmed SARS-CoV-2 infection, persistent symptoms at least 90 days after infection, and at least two clinic visits, including a baseline visit before starting the drug and a follow-up while taking it.
Brandon Aflak, who presented the work in Washington, said the group’s average seven-symptom composite score fell by an estimated 5.1 points after adjustment for other factors, with a 95% CI of -7.69 to -2.52 and P<0.001. The number of symptoms declined by a mean annual change of 2.4, and self-reported function rose as symptom burden eased. On the 1 to 5 functional stage scale, the adjusted mean annual change was 0.32, with a 95% CI of -0.57 to -0.07 and P=0.011.
The people in the study were not a random sample of all long COVID patients. Their median age was 45.4 years, 67% were female and 85.2% were fully vaccinated for COVID-19. Most had been infected with Omicron, at 70.9%, and the median time from COVID-19 infection to starting naltrexone was 606 days. They began with a median of 12 symptoms and a seven-symptom composite score of 20, then reached a median final dose of 4 mg.
That matters because low-dose naltrexone is being used off-label even though it is not approved for long COVID. Naltrexone itself is an opioid antagonist approved by the FDA for opioid use disorder and alcohol use disorder, and in combination with bupropion for obesity. Below the approved 50-100 mg range, it has also been used in conditions including multiple sclerosis, fibromyalgia, Crohn's disease and pain management.
Still, the design leaves a gap that the results cannot fill. A retrospective cohort can show that symptoms moved in the same period after treatment, but without a control group it cannot prove the drug caused the improvement. Aflak said that limitation matters and that randomized, placebo-controlled trials are needed to establish safety and efficacy and to define where, if anywhere, the drug fits in care.
That question has gained urgency because long COVID remains common. A 2022 survey found that 6.9% of U.S. adults said they had ever had it and 3.4% said they had it that year. For now, the study strengthens the case for testing low-dose naltrexone more rigorously, not for calling it a proven answer.
