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## **Autonomic Nervous System Dysregulation in Young People with a History of COVID-19**

**Ekaterina Zavgorodnyaya1 , Svetlana Tymchenko2 , and Anna Bogdanova2** <sup>1</sup> Federal Health Center "Burevestnik", Evpatoriya, Russian Federation <sup>2</sup> V.I. Vernadsky Federal University, Simferopol, Russian Federation

Increasing numbers of COVID-19 patients continue to experience symptoms weeks and months after recovery. 'Long COVID' could be possibly related to a virus- or immune-mediated damage of the autonomic nervous system (ANS) responsible for adaptation as it regulates vital functions such as cardiovascular and respiratory, most commonly affected by COVID-19. However, the involvement of ANS in post-COVID, expressed by dysautonomia, has not been studied well.

The objectives of this pilot study were to: Study the features of heart rate variability (HRV) in young people as a marker of ANS activity. Evaluate the differences in HRV in subjects with and without a history of COVID-19. A total of 32 healthy young people (18.4 ± 0.8 y/o) were tested in September 2020. Upon re-registration in February 2021, the subjects were divided into groups: 1st - 13 people (five females) with a history of COVID-19; 2nd (control) - 19 individuals (12 females) without prior infection.

The state of the ANS was assessed by the HRV recorded at rest and during the orthostatic test (Varicard 2.6, Russia). Statistical analysis was performed using the software StatTech v. 1.2.0 (LLC "StatTech", Russia). HRV recordings in February during the orthostatic test in group 1 revealed increased parasympathetic (RMSSD, HF) indices compared to September recordings (0.003 ≤ p ≤ 0.037) and lower HR and LF/HF values (0,019 ≤ р ≤ 0,034). The values of Xmax, MxDMn, MxMn, and HF were higher (0.012 ≤ p ≤ 0.033) in subjects with a history of COVID-19, and AMo50% (p = 0.024), SI (p = 0.006) were lower compared to the controls suggesting greater activity of the parasympathetic nervous system in group 1 during the orthostatic test. These results indicate dysregulation of autonomic cardiac control during orthostatic tests in individuals with a history of COVID-19. Post- COVID HRV dysregulation may explain some of the persistent symptoms, such as tachycardia, palpitations, and orthostatic intolerance. Monitoring the state of ANS via HRV is important for understanding the pathophysiology of this condition and for predicting complications.

Ekaterina Zavgorodnyaya1, Svetlana Tymchenko2, and Anna Bogdanova2

<sup>1</sup> Federal Health Center "Burevestnik", Evpatoriya, Russian Federation 2 V.I. Vernadsky Federal University, Simferopol, Russian Federation

#### Introduction

Increasing numbers of COVID-19 patients continue to experience symptoms weeks and months after recovery. 'Long COVID' could possibly be related to virus- or immune-mediated damage of the autonomic nervous system (ANS) responsible for adaptation, as it regulates vital functions such as cardiovascular and respiratory mechanisms, most commonly affected by COVID-19. However, the involvement of ANS in post-COVID, expressed by dysautonomia, has not been studied well.

#### Objectives


#### Methodology

Total of 32 healthy young people (18.4 ± 0.8 years old).

The state of the ANS was assessed using the HRV 5 minute recordings at rest and during the orthostatic test (Varicard 2.6, Russia).

Statistical analysis was performed using StatTech v.1.2.0 software (LLC "StatTech", Russia).

### Results and Discussion

HRV recordings (Figure 1) in February during the orthostatic test in group 1 revealed increased parasympathetic (RMSSD, HF) indices compared to September's recordings (0.003 ≤ p ≤ 0.037) and lower HR and LF/HF values (0,019 ≤ p ≤ 0,034).

*Figure 1. Dynamics of HRV parameters (RMSSD, HF, HR) in subjects without (0) and with (1) a past history of COVID-19.*

#### Results and Discussion

RMSSD increased from 23 (16 - 39) ms to 33 (24 - 47) ms (p = 0.037), and HF from 365 (174 - 549) to 492 (276 - 883) ms2 (p = 0.021).

The values of Xmax, MxDMn, MxMn and HF were higher (0.012 ≤ p ≤ 0.033) in subjects with a history of COVID-19, and AMo50% (p = 0.024) and SI (p = 0.006) were lower (Figure 2) compared to the controls, suggesting greater activity of the parasympathetic nervous system in group 1 during the orthostatic test.

Gender differences revealed that RMSSD, pNN50, SDNN, TP and HF were 1.3–5 times higher in men (0.002 ≤ p ≤ 0.025) than in women during the orthostatic test in group 1.

*Figure 2. Dynamics of HRV parameters (MxDMn, AMo) in subjects without (0) and with (1) a past history of COVID-19.*

These results indicate a dysregulation of autonomic cardiac control during the orthostatic test in individuals with a history of COVID-19. Naturally, sympathetic function increases immediately after changing to a standing position. Clinical data suggest that people with COVID-19 show a higher sympathetic nervous system tone during the acute infection, and in early days and weeks in the convalescence, as well. Later on during the course of the disease, there might be a reactive 'overshoot' of parasympathetic activity.

#### Conclusions

Post-COVID HRV dysregulation may explain some of the persistent symptoms, such as fatigue, dizziness, palpitations and orthostatic intolerance. Prolonged parasympathetic activity might be responsible for these symptoms. HRV is a simple, non-invasive and validated measure for the assessment of the ANS function. Monitoring the state of ANS via HRV is important for understanding the pathophysiology of "long COVID" and for predicting complications.

#### Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this article.
