Autonomic Nervous System Affection Due to Post Covid Syndrome

Study Overview
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Brief Summary
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Post-Covid syndrome is defined as symptoms that develop in addition to respiratory symptoms in individuals who have had Covid-19 infection for more than 12 weeks. Symptoms such as fatigue, headache, cognitive impairment, dyspnea, heart palpitations, heat intolerance, digestive system disorders, sleep disorders, dermal problems, orthostatic intolerance come to the fore in individuals with post-Covid syndrome. It has been tried to be revealed in some studies that Covid-19 infection affects the autonomic nervous system (ANS) and the relationship between Post-Covid 19 syndrome and ANS dysfunction. Heart rate variability (HRV) measurement method can be used to evaluate ANS activity. HRV is a non-invasive method and is a measure of the change in heart rate over a period of time. HRV is a scalar quantity that shows the time between two beats of the heart and defines the oscillations between the R-R intervals. In HRV measurements, time-dependent and frequency-dependent measurement results are obtained and from these measurements, time-dependent RMSSD (square root of the square of the difference of the R-R intervals) and frequency-dependent high-frequency (HF) and low frequency (LF) measurement components are used in relation to the sympathetic nervous system (CNS) and parasympathetic nervous system (PSS). HRV can be measured in short-term (5 minutes) in terms of measurement time. The aim of this study is to clearly reveal the relationship between Post-Covid 19 syndrome and ANS dysfunction and to provide standardization related to HRV measurement method and sub-parameters.

Detailed Description
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SARS-CoV-2 virus emerged with severe acute respiratory tract infection and pneumonia when turned into a chronic disease that can cause permanent symptoms in recovering individuals. Prolonged Covid-19 syndrome or Post-Covid 19 syndrome is defined as symptoms that develop in addition to respiratory symptoms in individuals who have had Covid-19 infection for more than 12 weeks. Symptoms such as fatigue, headache, cognitive impairment, dyspnea, heart palpitations, heat intolerance, digestive system disorders, sleep disorders, dermal problems, orthostatic intolerance come to the fore in individuals with post-Covid syndrome. It has been tried to be revealed in some studies that Covid-19 infection affects the autonomic nervous system (ANS) and the relationship between Post-Covid 19 syndrome and ANS dysfunction. It is known that the cytokine storm caused by Covid-19 is caused by sympathetic activation that induces the release of proinflammatory cytokines, and the virus is associated with autoantibodies such as α(alpha) and β(beta) adrenoceptors and muscarinic receptors and in this case it causes autoimmunological disorder and ANS dysfunction. ANS consists of craniosacral parasympathetic fibers and cervicothoracic sympathetic fibers and consists of a complex network structure that provides homeostasis of the body. The parasympathetic nervous system predominates in quiet rest and digest conditions, while the sympathetic nervous system drives the fight or flight response in stressful situations. Heart rate variability (HRV) measurement method can be used to evaluate ANS activity. HRV is a non-invasive method and is a measure of the change in heart rate over a period of time. HRV is a scalar quantity that shows the time between two beats of the heart and defines the oscillations between the R-R intervals. In HRV measurements, time-dependent and frequency-dependent measurement results are obtained and from these measurements, time-dependent RMSSD (square root of the square of the difference of the R-R intervals) and pNN50 (the proportionality coefficient obtained by dividing the total number of R-R intervals by NN50), frequency-dependent high-frequency (HF) and low frequency (LF) measurement components are used in relation to the sympathetic nervous system (CNS) and parasympathetic nervous system (PSS). HRV can be measured in 3 different ways, as ultra short-term (<5 minutes), short-term (5 minutes) and long-term (24 hours), in terms of measurement time, and these values provide different results from each other. While 24-hour long-term measurements are preferred in cardiac diseases with a risk of mortality, short-term and ultra short-term measurements may be preferred in measuring the effect of chronic and metabolic diseases on HRV. The aim of this study is to clearly reveal the relationship between Post-Covid 19 syndrome and ANS dysfunction and to provide standardization related to HRV measurement method and sub-parameters. Our study in which investigated the effect of post-Covid 19 syndrome on the autonomic nervous system, will be carried out in the Bahçeşehir University Institute of Health Sciences. Written consent will be obtained from the participants, indicating that they agreed to participate in the study and the content of the study was presented verbally and in writing form. Patients will be taken a short 5-minute measurement for HRV measurement once during the study. Before the evaluation, sociodemographic information will be obtained from the participants in the form of a questionnaire and the symptoms experienced by the participants were recorded. Participants will be warned not to exert excessive effort and not to take any medication or treatment before the measurement. In the research form given to the patients, the symptoms of individuals with Post-Covid 19 syndrome will be marked and the percentage of these symptoms was calculated. These symptoms will be determined as fatigue, headache, cognitive impairment, dyspnea, heart palpitation, heat intolerance, digestive system disorders, sleep disturbance, dermal problems, orthostatic intolerance. A total of 60 participants whom between the ages of 18-45 will include in our study, including 20 participants (n=20) who experience Post-Covid 19 syndrome, participants who fully recover after Covid-19 (n=20) and participants who has never have Covid-19 (n=20). In order for the study groups to be homogeneous, the ratio of the number of men and women in the groups will tried to be equal. The Polar H10 wearable HRV measurement technology, which we use in our study and produced by Polar Electro company, is a device that helps to measure the R-R interval at rest and at different activity intensities (Picture 1). In the study conducted by Schweizer et al., it shows that the Polar H10 device had 99.6% R-R interval signal quality during 5 different activities (16). In our research, the measurements will made with the Polar H10 device were analyzed on the computer with the Kubios Software 3.5.0 program (https://www.kubios.com). With this program, it is possible to apply time dependent, frequency dependent and nonlinear analysis method.

Official Title
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Identification of the Effects of Post Covid Syndrome on the Autonomic Nervous System With Heart Rate Variability

Conditions
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Long Covid19, Autonomic Dysfunction

Intervention / Treatment
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* Other: Heart Rate Variability Measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who aged 18-45 years Exclusion Criteria: Considering that the estrogen level in the body affects ANS among female patients, female participants in pre-menopausal, post-menopausal and pregnancy conditions Being in the date of women in the menstruation period Cancer diagnosis and treatment, Neurological disease diagnosis, Immunological disease diagnosis, History of cardiovascular disease diagnosis Presence of acute infection Participants who used medication in the last 6 months for the treatment of ANS dysfunction were also excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Participants who experienced Post-Covid 19 syndrome were involved in this group. | Other: Heart Rate Variability Measurement<br>* The heart rate variability of the participants will be measured with the Polar H10 device with a measurement time of 5 minutes.<br>|
| Group 2<br>Participants who fully recovered after Covid-19 were involved in this group. | Other: Heart Rate Variability Measurement<br>* The heart rate variability of the participants will be measured with the Polar H10 device with a measurement time of 5 minutes.<br>|
| Group 3<br>Participants who had never had Covid-19 were involved in this group. | Other: Heart Rate Variability Measurement<br>* The heart rate variability of the participants will be measured with the Polar H10 device with a measurement time of 5 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate Variability-Time Dependent(RMSSD) | RMSSD: Root mean square of successive RR interval differences. Unit: miliseconds(ms) | Through study completion, an average of 1 year. | 
| Heart Rate Variability-Frequency Dependent- Low Frequency (LF) Power | Low Frequency Power (LF): Relative power of the low-frequency band (0.04-0.15 Hz) in normal units. Unit: nu | Through study completion, an average of 1 year. | 
| Heart Rate Variability-Frequency Dependent- High Frequency (HF) Power | High Frequency (HF) Power: Relative power of the high-frequency band (0.15-0.4 Hz) in normal units. Unit:nu | Through study completion, an average of 1 year. | 
| Heart Rate Variability-Frequency Dependent- High Frequency (HF)/ Low Frequency(HF/LF) | High Frequency (HF)/ Low Frequency(HF/LF): Ratio of LF-to-HF power. Unit: % | Through study completion, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body mass index (BMI) | BMI = kg/m2 where kg is a person's weight in kilograms and m2 is their height in metres squared. | Through study completion, an average of 1 year. |