COVID-19 Dysautonomia: An Important Component of “Long-Hauler Syndrome”

We have obtained a wealth of knowledge about COVID-19 over the last year, and the pace of developing therapeutics and very effective vaccines have been impressive. However, as our experience with COVID-19 accrues, so does our knowledge of its long-term sequalae. Thus, we are left expectantly wondering what “time will tell.” Such has been our experience with post-COVID-19 dysautonomia.

In cardiology and electrophysiology, treating postural orthostatic tachycardia syndrome (POTS), a form of dysautonomia, is as vexing as it is complex. “Long-hauler syndrome” is a post COVID-19 phenomenon describing a constellation of symptoms including fatigue, mental fog, behavioral and sleep disturbance, and poor exercise tolerance.¹ In the largest study of this syndrome to date, 76% of patients had persistent symptoms at 6 months following acute illness.² A troubling trend in “long-hauler syndrome” is the significant presence of dysautonomia and POTS. We will describe its proposed pathophysiology and our experience with these patients.

Pathophysiology

The following mechanisms have been proposed by expert opinion, but research is ongoing, and none have been verified by evidence to date.³ They are not mutually exclusive and may contribute in different ways to a patient’s presentation and course.

Two neurologic mechanisms have been proposed, affecting both the peripheral and central nervous systems. In the peripheral nervous system, the destruction of postganglionic sympathetic neurons may precipitate increased sympathetic tone on the heart in a mechanism similar to neuropathic POTS. In the central nervous system, damage to the brain stem may also precipitate centrally mediated sympathetic outflows to the heart. When considering effects on the central nervous system, this could also explain the commonly associated anxiety and depression.³

The above effects on the nervous system may occur by direct viral attack or autoimmune phenomena. POTS patients without a history of COVID-19 have demonstrated autoimmune antibodies and there is clearly a significant autoimmune component of COVID-19. The immune dysregulation in COVID-19 is believed to contribute heavily to its acute morbidity and likely has a significant impact on “long-hauler syndrome.”

Finally, the acute volume shifts associated with anorexia, nocturnal sweating, and febrile illness in COVID-19 could likely exacerbate dysautonomia symptoms. These issues combined with prolonged bedrest may exacerbate dysautonomia and the neurologic issues described here.³

Our Experience

The majority of patients who have received consultations for post-COVID-19 dysautonomia have been seen within the last 3 months. They are largely in a younger and healthier demographic (20s and 30s) who previously were leading active lifestyles. We have a smaller proportion of patients with comorbidities and an older demographic.

The onset of symptoms occurs often within the last week of the illness, but we have also seen symptom onset occur within 3 months of recovery. We have an equal distribution of male and female patients, which is much different than our typical experience with neurogenic POTS.

Common symptoms reported are erratic heart rates with minimal positional changes or activity. We have found patients who previously led very active lifestyles find these symptoms exceptionally disconcerting and have difficulty resuming exercise. Our experience may be skewed by the active Colorado demographic.

As cases become more severe, exertional chest pain and erratic blood pressure with associated extreme hypertension (systolic blood pressure as high as 190 mmHg) may be present. In our limited experience, male patients tend to have a more severe yet still benign course. Generally, female and older demographic patients tend to have a less severe yet significant presentation.

Our workup generally consists of an EKG, echocardiogram, and event monitor. If there are significant symptoms of chest pain, a cardiac MRI with and without contrast is ordered. We have not found any arrhythmias, cardiomyopathy, or late gadolinium enhancement in any of our patients, and example studies are presented in Figures 1 and 2. Event monitors do reveal periods of sinus tachycardia with minimal provocation (Figure 2).

Our first-line approach is to increase hydration and recumbent exercise. If patients have low or normal blood pressure, we encourage 3-5 grams of salt intake. In more severe cases where hypertension has occurred, increased salt intake is not encouraged. Exercise is first encouraged recumbently through stretching, biking, strength training, and yoga. As symptoms improve, standing or exercising with positional changes may be pursued.

In more severe cases with significant hypertension, we have had success with acebutolol starting at the 200 mg dose and titrating up over a period of weeks as needed. Medications are combined with the above behavioral changes. We have noted much more anxiety in severe patients. It is unclear whether the anxiety is reactive, part of the larger syndrome, or triggered by more severe symptoms. Anxiety has been treated by exercise, therapy, and medication as needed.

Overall, albeit with short-term follow-up over a period of weeks to months, these symptoms appear to gradually improve with relatively conservative management. The behavioral changes appear to avoid hypovolemia while exercises gradually retrain the autonomic balance. We have not yet had a patient’s symptoms completely resolve, but each appointment usually heralds gradual improvement on an individualized timeline.

Summary

The emergence of “long-hauler” syndrome post COVID-19 is disconcerting with significant prevalence in younger populations. Awareness of this syndrome and further characterization is critical. Early reports indicate that vaccination may improve these symptoms by unclear mechanisms.⁴ Vaccination when eligible combined with conservative management is our approach. In time, further insights and patterns of the “long-hauler” syndrome must be investigated and disseminated. Although the medical community may seem familiar with the effects of COVID-19, we as a medical community are only uncovering its many sequalae. 

Disclosures: The authors have no conflicts of interest to report regarding the content herein.

1. Horwitz R, Maizes V. Integrative medicine and the long hauler syndrome-we meet again. Am J Med. 2020 Dec 31;S0002-9343(20)31171-2.
2. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397:220-232.
3. Goldstein DS. The possible association between COVID-19 and postural tachycardia syndrome. Heart Rhythm. 2020 Dec 11;S1547-5271(20)31141-3.
4. Wetsman N. Long COVID patients say they feel better after getting vaccinated: The shots might help people with chronic symptoms. The Verge. Published March 2, 2021 Accessed March 10, 2021. https://www.theverge.com/2021/3/2/22308965/covid-vaccine-shots-symptoms-improve-chronic-long-haulers