Low-Dose Naltrexone use for the management of post-acute sequelae of COVID-19

Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as Long COVID, is globally estimated to have affected up to 40-50% of individuals who were infected with SARS-CoV-2. The causes of PASC are being investigated, and there are no established therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increased systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. In this study we performed retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with improved clinical symptoms (fatigue, brain fog, post exertional malaise/PEM, unrefreshing sleep, sleep pattern, and headache), fewer number of symptoms, and better functional status. This observational finding warrants further testing in rigorous, randomized, placebo-controlled clinical trials. Highlights ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Stanford IRB protocol 62996 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes It will be included as a supplementary material.