Randomized Controlled Trials for Post-COVID-19 Conditions: A Systematic Review.

Post-coronavirus disease 2019 (COVID-19) syndrome or condition (PCS) is defined as new onset symptoms for at least three months following COVID-19 infection that has persisted for at least two months. Given the global sequelae of COVID-19, there is an urgent need for effective PCS interventions. The aim of this study was to systematically review all interventions for PCS tested in randomized controlled trials. In this International Prospective Register of Systematic Reviews (PROSPERO) registered (CRD42023415835) systematic review, PubMed, Google Scholar, and ClinicalTrials.gov databases were searched between 1st January 2020 and 30th April 2023. Inclusion criteria were (1) randomized controlled trials that tested interventions for (2) PCS as defined above. Studies were independently reviewed, and final decisions regarding extracted data and risk of bias were made by consensus. Trial findings were summarized qualitatively. The review included 23 trials with 1,916 subjects (mean age 44.9, 25.8% males) from 10 countries. The predominant symptom or function targeted by the interventions were general long COVID-19 symptoms (35%), fatigue (30%), breathlessness (17%), olfactory (17%), and brain function (9%). Overall, the majority of trials (74%) were at high risk of bias. A range of interventions were identified, including physical therapies, dietary and regenerative treatments, electrical stimulation, and digital wellness programs with variable effects. While a diverse range of interventions for PCS have been tested, their effectiveness varies, with threats to validity in most studies. Trials focusing on PCS mental health disorders, musculoskeletal complaints, and children are needed. Well-designed RCTs are needed to establish definitive interventions for PCS.