Treatments for Long COVID Autonomic Dysfunction: a Scoping Review

Purpose: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies.

Methods: 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 We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform).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.

Results: 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 The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin.

Conclusion: 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 Unpublished/ongoing studies may shed light on this critical area of patient management.