Prospective Evaluation of Autonomic Dysfunction in Post-Acute Sequela of COVID-19

Sameer M. Jamal, MD; David B. Landers, MD; Steven M. Hollenberg, MD; Zoltan G. Turi, MD; Taya V. Glotzer, MD; Jana Tancredi, RN, MA/MSN; Joseph E. Parrillo, MD


J Am Coll Cardiol. 2022;79(23):2325-2330. 

In This Article

Abstract and Introduction


Background: Patients with post-acute sequela of COVID-19 (PASC) often report symptoms of orthostatic intolerance and autonomic dysfunction. Numerous case reports link postural orthostatic tachycardia syndrome (POTS) to PASC. No prospective analysis has been performed.

Objectives: This study performed head-up tilt table (HUTT) testing in symptomatic patients with PASC to evaluate for orthostatic intolerance suggestive of autonomic dysfunction.

Methods: We performed a prospective, observational evaluation of patients with PASC complaining of poor exertional tolerance, tachycardia with minimal activity or positional change, and palpitations. Exclusion criteria included pregnancy, pre-PASC autonomic dysfunction or syncope, or another potential explanation of PASC symptoms. All subjects underwent HUTT.

Results: Twenty-four patients with the described PASC symptoms were included. HUTT was performed a mean of 5.8 ± 3.5 months after symptom onset. Twenty-three of the 24 had orthostatic intolerance on HUTT, with 4 demonstrating POTS, 15 provoked orthostatic intolerance (POI) after nitroglycerin, 3 neurocardiogenic syncope, and 1 orthostatic hypotension. Compared with those with POTS, patients with POI described significantly earlier improvement of symptoms.

Conclusions: This prospective evaluation of HUTT in patients with PASC revealed orthostatic intolerance on HUTT suggestive of autonomic dysfunction in nearly all subjects. Those with POI may be further along the path of clinical recovery than those demonstrating POTS.


Relatively little is known about the potential lasting impact of COVID-19. There is recognition of a debilitating post COVID-19 syndrome referred to as post-acute sequela of COVID-19 (PASC), defined as the presence of at least 1 clinical sequela at least 4 weeks after acute COVID-19 infection.[1–3] Although current PASC literature describes fatigue as a primary symptom, palpitations and orthostatic intolerance (OI) have also been reported, albeit less frequently.[4,5] The etiology of these symptoms is unknown, and a purported mechanism is dysregulation of the autonomic nervous system. Autonomic dysfunction associated with OI, including new-onset postural orthostatic tachycardia syndrome (POTS) in patients with PASC, has been described in case reports.[6–10] We identified patients with specific PASC symptoms following COVID-19 infection and report a prospective evaluation of OI in these patients.