Treatments for Long COVID autonomic dysfunction: a scoping review

For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies. We first interviewed 11 stakeholders (clinicians, clinician/researchers, payors, patient advocates) to gain clinical insights and identify key areas of focus. We searched Embase, CINAHL, Medline, PsycINFO, and PubMed databases for relevant English-language articles published between 1 January 2020 and 30 April 2024. We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform). All information was summarized narratively. We included 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine + famotidine, maraviroc + pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a nutraceutical (SIM01) on fatigue and gastrointestinal upset. The 11 guidelines and position statements addressed numerous aspects of treatment, but primarily exercise/rehabilitation, fluid/salt intake, and the use of compression garments. The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin. Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management.