Background: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.
Objective: To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.
Methods: Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.
Conclusion: This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.
Ethics and dissemination: The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.
