Introduction: The post-acute sequelae of COVID-19 (PASC) is a syndrome characterized by persistent COVID-19 symptoms or the onset of new symptoms following recovery from the initial or acute phase of the illness. Such symptoms often occur four or more weeks after being diagnosed with COVID-19. Although a lot of work has gone into understanding the long-term mental health effects of PASC, many questions related to the etiology and risk of this condition remain. Thus, this protocol is for a systematic review assessing the association between PASC and adverse psychiatric outcomes and whether people with PASC are at greater risk of developing an adverse psychiatric outcome than those without PASC.

Methods and analysis: Various medical databases (e.g., PubMed and EMBASE) will be searched for eligible articles using predefined search criteria. Gray literature will also be explored. Epidemiological observational studies and secondary analyses of randomized controlled trials that report a quantitative relationship between PASC and at least one adverse psychiatric outcome will be included. The Population, Exposure of interest, Comparator, and Outcome (PECO) framework will be used as a standardized framework for the inclusion criteria. The Joanna Briggs Institute (JBI) critical appraisal tools will be used to assess methodological quality and critically appraise the risk of bias in included studies. A random-effects meta-analysis will be conducted if possible. A narrative synthesis will be performed if a meta-analysis is impossible due to substantial heterogeneity across studies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to rate the cumulative certainty of the evidence for all outcomes.

Ethics and Dissemination: Ethical approval is not required for this study. The study results will be published in a peer-reviewed journal.