Autonomic dysfunction following COVID-19 infection: an early experience

Abstract

Purpose: Post-COVID-19 syndrome is a poorly understood aspect of the current pandemic, with clinical features that overlap with symptoms of autonomic/small fiber dysfunction. An early systematic analysis of autonomic dysfunction following COVID-19 is lacking and may provide initial insights into the spectrum of this condition.

Methods: We conducted a retrospective review of all patients with confirmed history of COVID-19 infection referred for autonomic testing for symptoms concerning for para-/postinfectious autonomic dysfunction at Mayo Clinic Rochester or Jacksonville between March 2020 and January 2021.

Results: We identified 27 patients fulfilling the search criteria. Symptoms developed between 0 and 122 days following the acute infection and included lightheadedness (93%), orthostatic headache (22%), syncope (11%), hyperhidrosis (11%), and burning pain (11%). Sudomotor function was abnormal in 36%, cardiovagal function in 27%, and cardiovascular adrenergic function in 7%. The most common clinical scenario was orthostatic symptoms without tachycardia or hypotension (41%); 22% of patients fulfilled the criteria for postural tachycardia syndrome (POTS), and 11% had borderline findings to support orthostatic intolerance. One patient each was diagnosed with autoimmune autonomic ganglionopathy, inappropriate sinus tachycardia, vasodepressor syncope, cough/vasovagal syncope, exacerbation of preexisting orthostatic hypotension, exacerbation of sensory and autonomic neuropathy, and exacerbation of small fiber neuropathy.

Conclusion: Abnormalities on autonomic testing were seen in the majority of patients but were mild in most cases. The most common finding was orthostatic intolerance, often without objective hemodynamic abnormalities on testing. Unmasking/exacerbation of preexisting conditions was seen. The temporal association between infection and autonomic symptoms implies a causal relationship, which however cannot be proven by this study.

Keywords: Autoimmune autonomic ganglionopathy; Autonomic diseases; COVID-19; Orthostatic intolerance; Postural orthostatic tachycardia syndrome.

Fig. 1

Thermoregulatory sweat test using alizarin red powder showing length-dependent anhidrosis of the fingers, left lower leg, and bilateral feet. The findings are consistent with length-dependent autonomic (small fiber) neuropathy. Hidrotic areas are colored in purple and anhidrotic areas in yellow; the face was not powdered

Fig. 2

Quantitative sudomotor axon reflex test showing relative distal (foot site) anhidrosis indicating distal autonomic (small fiber) neuropathy. Sweat output (µL): forearm site (red) 1.03 (5th percentile = 0.25), proximal leg (blue) 2.11 (5th percentile = 0.48), distal leg (green) 2.30 (5th percentile = 0.62), and foot (yellow) 0.26 (5th percentile = 0.15 and 10th percentile = 0.33)

Fig. 3

a Hemodynamic profile on head-up tilt study. Note prominent orthostatic tachycardia 129–42 bpm (green) and labile orthostatic hypotension (red) with systolic blood pressure change ranging from −14 to −34 mmHg. b Thermoregulatory sweat test showing widespread anhidrosis (73%) in a patchy pattern compatible with autonomic ganglionopathy