TL;DR
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In a retrospective study of 230 adults treated at Stanford’s Long COVID Clinic, patients reported fewer symptoms and better functional status after receiving low-dose naltrexone. Because the study had no control group, it cannot establish that the drug caused the changes or determine its safety and effectiveness for long COVID.
A retrospective study of 230 adults with long COVID found that patients reported fewer symptoms and improved functioning after receiving low-dose naltrexone, but the study’s design cannot show that the medication caused those changes. The findings were presented at the IDWeek annual meeting and add observational evidence on an off-label treatment, not proof of effectiveness.
Researchers analyzed electronic health records from Stanford’s Long COVID Clinic for adults with laboratory-confirmed SARS-CoV-2 infection and symptoms persisting at least 90 days. Participants had to have a clinic visit before starting naltrexone and at least one follow-up visit while taking it. The records covered 2023 through December 2025, and the study was retrospective, meaning investigators reviewed care that had already occurred.
After adjustment for other factors, the average seven-symptom composite score, which was about 20 at baseline, fell by an estimated 5.1 points per year. The reported number of symptoms declined by an estimated 2.4 per year, while functional stage scores improved by 0.32 points per year on a five-point scale. These are modeled annual changes, not results from a controlled comparison.
Improvements were reported for fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. The analysis did not find significant improvement in headache or lightheadedness. The median final naltrexone dose was 4 milligrams, below the drug’s approved 50-to-100-milligram doses for other uses. The supplied report does not establish how many participants experienced side effects or provide a comparison of adverse events against an untreated group.
What the Findings Could Mean for Patients
The results may matter to people living with persistent symptoms because long COVID has no FDA-approved therapies, and treatment options remain limited. The reported changes across several symptoms and functioning measures give researchers a reason to test low-dose naltrexone in more rigorous studies. They do not establish that patients generally can expect the same improvements.
The scale of reported activity limitations in this clinic group underscores the impact being studied: at baseline, 55.7% reported reduced daily activity, 24.3% said they struggled with normal daily activities, and 8.3% described themselves as incapacitated and bedridden. Those figures describe this study population, not all people with long COVID. Because there was no control group, the observed changes could reflect other factors as well as treatment.
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How the Stanford Clinic Study Was Run
The study included adults with persistent symptoms at least 90 days after confirmed COVID-19 and at least two clinic visits, one before treatment and one or more during treatment. The median age was 45.4; 67% were female, 85.2% were fully vaccinated, and 70.9% had been infected with an Omicron variant. The median interval between infection and starting naltrexone was 606 days.
Naltrexone is an opioid antagonist approved for opioid use disorder and alcohol use disorder. In combination with bupropion, it is also used for obesity. Lower doses are prescribed off-label for other conditions. Brandon Aflak, a Stanford fellow who presented the study, said naltrexone might have anti-inflammatory and immunomodulatory effects relevant to long COVID; that possibility was not tested as a mechanism in this analysis.
Long COVID definitions vary. The National Academies of Sciences, Engineering, and Medicine defines it as a chronic condition following SARS-CoV-2 infection that lasts at least three months and can affect one or more organ systems. The report also notes that results from other treatment research have been mixed: in a study of nirmatrelvir-ritonavir, or Paxlovid, the active-treatment group did not outperform placebo.
“Although these findings are encouraging, this observational study design does limit causal inference.”
— Brandon Aflak, Stanford University fellow, as quoted in the MedPage Today report
What the Study Cannot Establish
The absence of a control group means researchers could not compare patients taking naltrexone with similar patients not taking it or receiving a placebo. Natural changes in long COVID symptoms, other treatments, and differences in follow-up could have contributed to the reported outcomes. Adjustment for other factors does not remove these limits or establish cause and effect.
The study also does not settle whether low-dose naltrexone is safe and effective for long COVID, which patients might benefit, what dose or treatment duration would be appropriate, or how durable any improvement may be. The findings came from patients who attended one specialty clinic and met specific record and visit requirements, so they may not represent everyone with long COVID. The report does not provide randomized evidence or a definitive account of treatment-related harms.
The Need for Controlled Trials
The next step identified by Aflak is a randomized, placebo-controlled trial designed to test whether low-dose naltrexone causes improvements, evaluate safety, and clarify its potential place in care. The supplied report does not name a planned trial, launch date, or expected results timeline. Until such evidence is available, the Stanford findings should be read as an association from clinical records rather than proof that the drug treats long COVID.
Key Questions
Did the study prove that low-dose naltrexone improves long COVID?
No. It found that patients reported fewer symptoms and better functioning after starting the drug, but the observational study had no control group and cannot show that naltrexone caused the changes.
Which symptoms improved in the analysis?
Researchers reported improvements in fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. They did not find significant improvements in headache or lightheadedness.
Was low-dose naltrexone approved for long COVID?
No. The report says there are no FDA-approved therapies for long COVID. Naltrexone is approved for other uses, while the lower doses in this study were prescribed off-label.
What research is needed next?
A randomized, placebo-controlled trial is needed to test whether the medication is effective and safe for long COVID and to determine its possible role in clinical care.
Source: rss
