Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies

Abstract

Introduction: On March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.

Objective: To conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.

Results: Autonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.

Conclusion: Symptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.

Keywords: POTS; Post-COVID-19 condition; diagnosis; dysautonomia; management; orthostatic intolerance syndromes; socioeconomic impact.

Figure 1

Flow chart of the study.

Figure 2

Proposed COVID-19 pathways to the central nervous system. Adapted from the article by Yachou Y et al. (26).

Figure 3

Main dysautonomic changes in severe COVID-19 infection. Information extracted from the text and based on the article by Rangon et al. (27). Upward and downward pointing arrows indicate increase and decrease, respectively. Double arrows indicate important variations. Recording hemodynamic changes and detailed neurologic examinations are both standard clinical practice but are of the utmost importance in patients with COVID-19 and manifestations suggestive of autonomic dysfunction.

Figure 4

General indications for examining chronic symptoms described after COVID-19 (61, 75, 85). DD, Differential diagnosis; ANAs, antinuclear antibodies; BP, Blood pressure; h, hours; ECG, electrocardiogram; min, minutes; HT, Hypertensive; hT, Hypotensive; HR, Heart Rate; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; CT, Computed Tomography; POTS, postural orthostatic tachycardia syndrome; COMPASS-31, Composite Autonomic Symptom Scale 31 questionnaire; NA, Noradrenaline; ADH, Vasopressin.