Authors' objectives: To determine if there is any evidence on the efficacy and/or effectiveness of low-dose naltrexone (LDN) in treating patients diagnosed with Post-COVID Conditions (Long COVID).

Authors' results and conclusions: A small (n=36) case series (level of evidence 4. Appendix 1) exploring the safety of LDN, as well as looking into symptomatic improvement and improvement in well-being in patients with long COVID was found, and was reviewed in our paper. In this study, patients were recruited from a hospital based COVID clinic. Patients who enrolled in this study received LDN 1 mg once daily for one month, then the dose was increased by 1 mg monthly to a maximum of 3 mg. At follow-up there was an improvement in six out of seven outcomes listed in the questionnaire. It should be noted that although this small case series reported improvement on the six (out of seven) components of outcomes measured, the results have to be interpreted with caution since bias (associated with unclear patient selection and loss to follow-up) as well as chance due to multiple comparison cannot be excluded from the reported outcomes. Further, the measured outcomes were subjective in nature and were only measured for a short time (2 months) post treatment. It should also be noted that many of the reported initial symptoms did not improve by the end of the follow-up. At present, there may be some low-level low-quality evidence on the effectiveness of low-dose naltrexone to treat post-COVID-19 patients. However, the available evidence has to be interpreted with caution due to the potential for bias and chance that cannot be excluded from affecting the observed outcomes. At present, there are two relevant randomized controlled trials (one is still at listing only and one has not reported the outcome although has finished recruitment) that we will follow up on to update this systematic review.

Authors' recommendations: A small (n=36) case series (level of evidence 4. Appendix 1) exploring the safety of LDN, as well as looking into symptomatic improvement and improvement in well-being in patients with long COVID was found, and was reviewed in our paper. In this study, patients were recruited from a hospital based COVID clinic. Patients who enrolled in this study received LDN 1 mg once daily for one month, then the dose was increased by 1 mg monthly to a maximum of 3 mg. At follow-up there was an improvement in six out of seven outcomes listed in the questionnaire. It should be noted that although this small case series reported improvement on the six (out of seven) components of outcomes measured, the results have to be interpreted with caution since bias (associated with unclear patient selection and loss to follow-up) as well as chance due to multiple comparison cannot be excluded from the reported outcomes. Further, the measured outcomes were subjective in nature and were only measured for a short time (2 months) post treatment. It should also be noted that many of the reported initial symptoms did not improve by the end of the follow-up. At present, there may be some low-level low-quality evidence on the effectiveness of low-dose naltrexone to treat post-COVID-19 patients. However, the available evidence has to be interpreted with caution due to the potential for bias and chance that cannot be excluded from affecting the observed outcomes. At present, there are two relevant randomized controlled trials (one is still at listing only and one has not reported the outcome although has finished recruitment) that we will follow up on to update this systematic review.

Authors' methods: A comprehensive and systematic literature search was conducted on commercial medical literature databases on December 16, 2022. No limitations, such as on the language of publication, were implemented in this literature search. A manual search on the references of the articles that were retrieved in full was also conducted.

Project Status: Completed

URL for project: https://www.worksafebc.com/en/about-us/research-services/evidence-based-medicine-and-systematic-reviews

Year Published: 2022

URL for published report: https://www.worksafebc.com/en/resources/health-care-providers/guides/low-dose-naltrexone-treatment-post-covid-conditions?lang=en

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Canada

Organisation Name: WorkSafeBC

Contact Address: 6591 Westminster Highway, Richmond, BC, V7C 1C6 Canada. Tel: 604-231-8417; Fax: 604-279-7698

Contact Name: ebpg@worksafebc.com

Contact Email: ebpg@worksafebc.com

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