Systematic review of randomized clinical trials for the treatment of long COVID syndrome

Background: There is a critical need for interventions for long COVID. Our aim was to conduct a systematic review on the efficacy and safety of different interventions in patients with long COVID. Methods: We searched the MEDLINE 1965 until August 2024. We included randomized clinical trials that reported a primary outcome. We evaluated the GRADE certainty of the effect measures. Results: Our initial search yielded 2,606 potentially relevant studies. We include 43 randomized clinical trials that ultimately included 2,878 participants with long COVID. The GRADE criteria found all but one study had low certainty. Eight studies reported on the use of nutraceuticals, 6 tested respiratory muscle training, 7 studies evaluated supervised exercise, 7 studies tested brain stimulation, and 5 studies used FDA regulated medications. The majority of the studies improved the primary outcome and included symptoms, quality of life, and exercise capacity. Conclusion: In randomized clinical trials medications, respiratory cognitive and physical therapy interventions improved outcomes in long COVID patients. However, the studies had low GRADE certainty of the effect measures. Larger and higher quality studies are needed.