Autonomic dysfunction following COVID-19 infection: an early experience

American Academy of Neurology (AAN) Journal:

Novel coronavirus disease (COVID-19) has been suggested to not only affect health during the acute phase of the SARS-CoV-2 infection, but some manifestations have been consistently reported also after the recovery. Such phenomenon has been named “long-COVID” or “post-acute COVID-19”.

These complications include myocarditis, pulmonary fibrosis, encephalitis, thromboembolic events, psychiatric illness, and persisting symptoms such as dyspnea, cough, and fatigue. Among these clinical manifestations, neurological symptoms may be also common, as cognitive deficits have been reported in 36% of patients two to four months after COVID-19.

Take Home Message:

Some recent studies have pointed a rationale for autonomic dysfunction following COVID-19, suggesting a role of the virus infection and/or of the related immune response on the autonomic nervous system (ANS), often resulting in orthostatic intolerance (OI), including orthostatic hypotension (OH) and postural tachycardia syndrome (POTS), fatigue, and activity intolerance as a post infectious complication of SARS-CoV-2.

The most commonly encountered clinical scenario was symptoms of orthostatic intolerance without demonstrable orthostatic tachycardia or orthostatic hypotension; these patients would best be categorized as having subjective orthostatic intolerance (OI).

OH and POTS can be common in the elderly, particularly in geriatrics outpatients, as well as in individuals with other dysautonomic features like in neurological diseases (e.g., Parkinson or dementia) or diabetes.

Post-COVID-19 POTS associated with other signs of autonomic dysfunction such as hyperhidrosis, phenomena such as small fiber neuropathy with orthostatic cerebral hypoperfusion syndrome, post-COVID-19 exacerbation of paroxysmal hypothermia and post-COVID-19 acute inflammatory demyelinating polyneuropathy (AIDP).

Patients infected with SARS-CoV-2 can develop a wide range of clinical manifestations including fatigue, myalgias, and gastrointestinal dysfunction. These in turn may lead to deconditioning, weight loss, and hypovolemia, which are known to predispose to orthostatic intolerance. It would therefore be expected that patients with a protracted course of COVID-19 infection or with lingering post infectious symptoms are at increased risk of developing orthostatic intolerance related to those factors.

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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 were seen. The temporal association between infection and autonomic symptoms implies a causal relationship, which however cannot be proven by this study.

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