Assessment of Autonomic Nervous System Dysfunction in the Early Phase of Infection With SARS-CoV-2 Virus

Branislav Milovanovic; Vlado Djajic; Dragana Bajic; Aleksandra Djokovic; Tatjana Krajnovic; Sladjana Jovanovic; Antonija Verhaz; Pedja Kovacevic; Miodrag Ostojic

doi:10.3389/fnins.2021.640835

Assessment of Autonomic Nervous System Dysfunction in the Early Phase of Infection With SARS-CoV-2 Virus

Front Neurosci. 2021 Jun 21:15:640835. doi: 10.3389/fnins.2021.640835. eCollection 2021.

Authors

Branislav Milovanovic^{1

2}, Vlado Djajic³, Dragana Bajic⁴, Aleksandra Djokovic^{2

5}, Tatjana Krajnovic⁶, Sladjana Jovanovic⁷, Antonija Verhaz³, Pedja Kovacevic³, Miodrag Ostojic^{3

8}

Affiliations

¹ Neurocardiology Lab, Department of Cardiology, University Hospital Medical Center Bezanijska kosa, Belgrade, Serbia.
² Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
³ Neurology Clinic, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina.
⁴ Faculty of Technical Sciences, University of Novi Sad, Novi Sad, Serbia.
⁵ Division of Interventional Cardiology, Department of Cardiology, University Hospital Medical Center Bezanijska kosa, Belgrade, Serbia.
⁶ Community Health Care Center "Dr J. J. Zmaj", Stara Pazova, Serbia.
⁷ Telekom Srbija a.d., Belgrade, Serbia.
⁸ Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia.

Abstract

Background: We are facing the outburst of coronavirus disease 2019 (COVID-19) defined as a serious, multisystem, disorder, including various neurological manifestations in its presentation. So far, autonomic dysfunction (AD) has not been reported in patients with COVID-19 infection.

Aim: Assessment of AD in the early phase of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus).

Patients and methods: We analyzed 116 PCR positive COVID-19 patients. After the exclusion of 41 patients with associate diseases (CADG), partitioned to patients with diabetes mellitus, hypertension, and syncope, the remaining patients were included into a severe group (45 patients with confirmed interstitial pneumonia) and mild group (30 patients). Basic cardiovascular autonomic reflex tests (CART) were performed, followed by beat-to-beat heart rate variability (HRV) and systolic and diastolic blood pressure variability (BPV) analysis, along with baroreceptor sensitivity (BRS). Non-linear analysis of HRV was provided by Poincare Plot. Results were compared to 77 sex and age-matched controls.

Results: AD (sympathetic, parasympathetic, or both) in our study has been revealed in 51.5% of severe, 78.0% of mild COVID-19 patients, and the difference compared to healthy controls was significant (p = 0.018). Orthostatic hypotension has been established in 33.0% COVID-19 patients compared to 2.6% controls (p = 0.001). Most of the spectral parameters of HRV and BPV confirmed AD, most prominent in the severe COVID-19 group. BRS was significantly lower in all patients (severe, mild, CADG), indicating significant sudden cardiac death risk.

Conclusion: Cardiovascular autonomic neuropathy should be taken into account in COVID-19 patients' assessment. It can be an explanation for a variety of registered manifestations, enabling a comprehensive diagnostic approach and further treatment.

Keywords: COVID-19; autonomic nervous system; autonomic neuropathy; cardiovascular reflex test; heart rate variability.