Evaluation of the long-term autonomic dysfunction after the recovery of COVID-19 disease

Year 2025, , 72 - 76, 10.01.2025

Ajar Koçak , Sezen Uzunget , Kader Eliz Şahin

https://doi.org/10.38053/acmj.1600205

Abstract

Aims: Beyond the acute phase of the COVID-19 disease, many patients experience persistent symptoms, collectively termed "post-COVID syndrome," which includes autonomic dysfunction. Heart rate variability (HRV) is a well-established method to assess autonomic nervous system (ANS) function. This study aimed to investigate the long-term impact of COVID-19 on autonomic function through evaluating the changes in HRV.
Methods: This retrospective study included 225 participants divided into two groups: 117 post-COVID patients and 108 age and gender matched controls. HRV was assessed using 24-hour Holter monitoring. Time-domain and frequency-domain indices were analyzed, including standard deviation of normal-to-normal intervals (SDNN), root mean square of successive RR interval differences (RMSSD), and low frequency (LF)/high frequency (HF) ratio. Statistical comparisons were performed using independent t-tests, Mann-Whitney U tests, and correlation analyses.
Results: Post-COVID patients exhibited significantly lower HRV indices compared to controls. Time-domain metrics such as SDNN (135.7±39.5 ms vs 149.1±34.2 ms, p=0.007) and RMSSD (32.7±13.7 ms vs 37.5±14.7 ms, p=0.012) were reduced in the COVID-19 group. Frequency-domain indices, including total power (TP) and HF power, were also diminished. Correlation analysis revealed no significant association between the duration of time post-COVID (one-year follow-up) and most HRV parameters.
Conclusion: Post-COVID patients experience significant autonomic dysfunction, marked by reduced parasympathetic activity and increased cardiovascular risks, with some evidence of partial recovery during sleep. Routine HRV monitoring and targeted interventions, alongside further research with larger cohorts, are crucial for better understanding of the long-term effects and improving patient outcomes.

Keywords

Post-COVID syndrome, autonomic dysfunction, heart rate variability

Ethical Statement

The study was conducted following the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from Adiyaman University ethics committee (Document No: 2022/6-4). All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors indicate no financial support or financial conflict of interest. The authors have indicated they have no financial relationships with any company and no external funding.

Supporting Institution

None

Thanks

None

References

• World Health Organization. Coronavirus disease 2019 (COVID-19): situation report, 51. World Health Organization. (https://iris.who.int/handle/10665/331475), 2020.
• Zhou F, Takata Y, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with covid-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054-1062.
• Zhu N, Zhang D, Wang W, et al. China novel coronavirus investigating and research team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-733.
• Carfì A, Bernabei R, Landi F. Gemelli Against COVID-19 post-acute care study group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603-605.
• Auwaerter PG. The race to understand post-COVID-19 conditions. Ann Intern Med. 2021;174(10):1458-1459.
• Dani M, Dirksen A, Taraborrelli P, et al. Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clin Med (Lond). 2021;21(1):e63-e67.
• Kutluk A, Tsuji T, Ukawa T, et al. A novel online method to monitor autonomic nervous activity based on arterial wall impedance and heart rate variability. Med Biol Eng Comput. 2010;48(4):351-359.
• Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981;213(4504):220-222.
• Grégoire JM, Gilon C, Carlier S, Bersini H. Autonomic nervous system assessment using heart rate variability. Acta Cardiol. 2023;78(6):648-662.
• Nunan D, Sandercock GR, Brodie DA. A quantitative systematic review of normal values for short-term heart rate variability in healthy adults. Pacing Clin Electrophysiol. 2010;33(11):1407-1417.
• Wu L, Jiang Z, Li C, Shu M. Prediction of heart rate variability on cardiac sudden death in heart failure patients: a systematic review. Int J Cardiol. 2014;174(3):857-860.
• Lee CCE, Ali K, Connell D, et al. COVID-19-associated cardiovascular complications. Diseases. 2021;9(3):47.
• Shah B, Kunal S, Bansal A, et al. Heart rate variability as a marker of cardiovascular dysautonomia in post-COVID-19 syndrome using artificial intelligence. Indian Pacing Electrophysiol J. 2022;22(2):70-76.
• DosSantos MF, Devalle S, Aran V, et al. Neuromechanisms of SARS-CoV-2: a review. Front Neuroanat. 2020;14:37.
• Hawerkamp HC, Dyer AH, Patil ND, et al. Characterisation of the pro-inflammatory cytokine signature in severe COVID-19. Front Immunol. 2023;14:1170012.
• Nadwa EH, Al-Kuraishy HM, Al-Gareeb AI, et al. Cholinergic dysfunction in COVID-19: frantic search and hoping for the best. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(3):453-468.
• Mancia G, Grassi G. The autonomic nervous system and hypertension. Circ Res. 2014;114(11):1804-1814.
• Shah AS, Lampert R, Goldberg J, et al. Alterations in heart rate variability are associated with abnormal myocardial perfusion. Int J Cardiol. 2020;305:99-105.
• Faria D, Moll-Bernardes RJ, Testa L, et al. Sympathetic neural overdrive, aortic stiffening, endothelial dysfunction, and impaired exercise capacity in severe COVID-19 survivors: a mid-term study of cardiovascular sequelae. Hypertension. 2023;80(2):470-481.
• Asarcikli LD, Hayiroglu Mİ, Osken A, Keskin K, Kolak Z, Aksu T. Heart rate variability and cardiac autonomic functions in post-COVID period. J Interv Card Electrophysiol. 2022;63(3):715-721.
• Lampsas S, Oikonomou E, Souvaliotis N, et al. Impaired heart rate variability one and six months post acute COVID-19. Eur Heart J. 2022;43(Suppl 2):ehac544.402.