The prevalence of orthostatic intolerance, postural orthostatic tachycardia syndrome and orthostatic hypotension in post-acute sequelae of COVID-19

Background: The COVID-19 pandemic has resulted in over 776 million confirmed cases worldwide, with post-acute sequelae of COVID-19 now recognized as a significant public health concern. Autonomic dysfunction-including orthostatic intolerance (OI), postural orthostatic tachycardia syndrome (POTS), and orthostatic hypotension (OH)-constitutes a major complication of post-acute sequelae of COVID-19. However, reliable epidemiological estimates remain scarce. As a result, we aim to provide the first global prevalence estimates of autonomic dysfunction in post-acute sequelae of COVID-19. Methods: This systematic review and meta-analysis adhered to PRISMA 2020 guidelines, including 21 observational studies. Random-effects models were utilized to estimate pooled prevalence, and sensitivity and meta-regression analyses were conducted to explore heterogeneity. GRADE assessments evaluated evidence certainty. Results: The pooled prevalence estimates demonstrated 70.6% for OI, 36.2% for POTS, and 18.6% for OH. Advancing age exhibited a significant negative association with POTS and OH. In contrast, prolonged post-acute sequelae of COVID-19 duration and female sex showed no significant association with the incidence rates of these conditions. Subgroup analyses indicated higher POTS and OH incidence in mild vs. moderate or severe COVID-19 cases. Publication bias was minimal for OH but evident for POTS. Conclusion: This study provides the first global prevalence estimates of autonomic dysfunction in post-acute sequelae of COVID-19, highlighting its disproportionate burden among younger populations and non-linear temporal trends. The findings advance epidemiological understanding and inform evidence-based public health strategies to address post-COVID complications. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=556546, PROSPERO CRD42024556546.