Persistent autonomic dysfunction following mild COVID-19: evidence from the orthostatic heart rate variability response
DOI:
https://doi.org/10.47197/retos.v77.117526Keywords:
Baroreflex Sensitivity, Cardiovascular Autonomic Control, COVID-19, Heart Rate VariabilityAbstract
Introduction: Autonomic alterations following COVID-19 have been reported in individuals with mild disease.
Objective: To investigate long-term effects of non-hospitalized COVID-19 on cardiovascular autonomic regulation, focusing on heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS).
Methodology: Eighty-five sedentary men aged 35–55 were allocated to CONTROL group (n = 43), assessed before the COVID-19 pandemic, and COVID-19 group (n = 42), evaluated at least six months after SARS-CoV-2 infection. Continuous recordings of heart rate and blood pressure were obtained in the supine position and during active standing. HRV, BPV, and BRS were analyzed using linear, nonlinear methods.
Results: Anthropometric and baseline hemodynamic variables did not differ between groups. In the supine position, HRV indices were comparable, except for approximate entropy in the COVID-19 group (1.46 ± 0.14 vs. 1.35 ± 0.13; p = 0.020). During orthostasis, the COVID-19 group showed reduced low-frequency (LF) oscillations of HRV (70 ± 17 vs. 81 ± 10%; p < 0.001), a lower LF/high-frequency ratio (4.12 ± 3.70 vs. 6.7 ± 4.4; p < 0.001), and decreased SD2 (standard deviation of long-term variability) from the Poincaré plot (45 ± 14 vs. 51 ± 19 ms; p = 0.048). BPV, BRS responses to postural stress were similar between groups.
Discussion: These findings indicate that individuals recovered from mild COVID-19 present subtle, persistent alterations in heart rate dynamics during postural challenge, suggesting incomplete autonomic adjustment to physiological stress.
Conclusion: Mild COVID-19 may be associated with persistent autonomic alterations during physiological stress.
References
Aghagoli, G., Gallo Marin, B., Katchur, N. J., Chaves-Sell, F., Asaad, W. F., & Murphy, S. A. (2021). Neurolo-gical Involvement in COVID-19 and Potential Mechanisms: A Review. Neurocritical Care, 34(3), 1062–1071. https://doi.org/10.1007/s12028-020-01049-4
Al-kuraishy, H. M., Al-Gareeb, A. I., Qusti, S., Alshammari, E. M., Gyebi, G. Ampoma., & Batiha, G. E.-S. (2021). Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm. ASN Neuro, 13, 175909142110576. https://doi.org/10.1177/17590914211057635
Asarcikli, L. D., Hayiroglu, M. İ., Osken, A., Keskin, K., Kolak, Z., & Aksu, T. (2022). Heart rate variability and cardiac autonomic functions in post-COVID period. Journal of Interventional Cardiac Elec-trophysiology, 63(3), 715–721. https://doi.org/10.1007/s10840-022-01138-8
Bairey Merz, C. N., Elboudwarej, O., & Mehta, P. (2015). The Autonomic Nervous System and Cardio-vascular Health and Disease. JACC: Heart Failure, 3(5), 383–385. https://doi.org/10.1016/j.jchf.2015.01.008
Billman, G. E. (2011). Heart Rate Variability ? A Historical Perspective. Frontiers in Physiology, 2. https://doi.org/10.3389/fphys.2011.00086
Bruce, Robert A. (1971). Exercise testing of patients with coronary heart disease. Principles and normal standards for evaluation. Annals of Clinical Research, 3, 323–332.
Cairo, B., Gelpi, F., Bari, V., Anguissola, M., Singh, P., De Maria, B., Ranucci, M., & Porta, A. (2025). A mod-el-based spectral directional approach reveals the long-term impact of COVID-19 on cardi-orespiratory control and baroreflex. BioMedical Engineering OnLine, 24(1), 8. https://doi.org/10.1186/s12938-024-01327-8
Carrasco, S., Gaitán, M. J., González, R., & Yánez, O. (2001). Correlation among Poincaré plot indexes and time and frequency domain measures of heart rate variability. Journal of Medical Engineering & Technology, 25(6), 240–248. https://doi.org/10.1080/03091900110086651
Castiglioni, P., & Faini, A. (2019). A Fast DFA Algorithm for Multifractal Multiscale Analysis of Physio-logical Time Series. Frontiers in Physiology, 10, 115. https://doi.org/10.3389/fphys.2019.00115
Chu, H., Chan, J. F.-W., Yuen, T. T.-T., Shuai, H., Yuan, S., Wang, Y., Hu, B., Yip, C. C.-Y., Tsang, J. O.-L., Huang, X., Chai, Y., Yang, D., Hou, Y., Chik, K. K.-H., Zhang, X., Fung, A. Y.-F., Tsoi, H.-W., Cai, J.-P., Chan, W.-M., … Yuen, K.-Y. (2020). Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmis-sibility, and laboratory studies of COVID-19: An observational study. The Lancet Microbe, 1(1), e14–e23. https://doi.org/10.1016/s2666-5247(20)30004-5
Dani, M., Dirksen, A., Taraborrelli, P., Torocastro, M., Panagopoulos, D., Sutton, R., & Lim, P. B. (2021). Autonomic dysfunction in ‘long COVID’: Rationale, physiology and management strategies. Clin-ical Medicine, 21(1), e63–e67. https://doi.org/10.7861/clinmed.2020-0896
Ding, K., Tarumi, T., Wang, C., Vernino, S., Zhang, R., & Zhu, D. C. (2020). Central autonomic network functional connectivity: Correlation with baroreflex function and cardiovascular variability in older adults. Brain Structure and Function, 225(5), 1575–1585. https://doi.org/10.1007/s00429-020-02075-w
Dutra, S. G. V., Pereira, A. P. M., Tezini, G. C. S. V., Mazon, J. H., Martins-Pinge, M. C., & Souza, H. C. D. (2013). Cardiac Autonomic Modulation Is Determined by Gender and Is Independent of Aerobic Physical Capacity in Healthy Subjects. PLoS ONE, 8(10), e77092. https://doi.org/10.1371/journal.pone.0077092
Facioli, T. P., Gastaldi, A. C., Dutra, S. G. V., Felix, A. C. S., Philbois, S. V., Sánchez-Delgado, J. C., & Souza, H. C. D. (2018). The blood pressure variability and baroreflex sensitivity in healthy participants are not determined by sex or cardiorespiratory fitness. Blood Pressure Monitoring, 23(5), 260–270. https://doi.org/10.1097/MBP.0000000000000338
Fedorowski, A., Fanciulli, A., Raj, S. R., Sheldon, R., Shibao, C. A., & Sutton, R. (2024). Cardiovascular au-tonomic dysfunction in post-COVID-19 syndrome: A major health-care burden. Nature Reviews Cardiology, 21(6), 379–395. https://doi.org/10.1038/s41569-023-00962-3
Gibbons, C. H. (2019). Basics of autonomic nervous system function. Em Handbook of Clinical Neurol-ogy (V. 160, p. 407–418). Elsevier. https://doi.org/10.1016/B978-0-444-64032-1.00027-8
Guzzetti, S., Borroni, E., Garbelli, P. E., Ceriani, E., Bella, P. D., Montano, N., Cogliati, C., Somers, V. K., Mal-lani, A., & Porta, A. (2005). Symbolic Dynamics of Heart Rate Variability: A Probe to Investigate Cardiac Autonomic Modulation. Circulation, 112(4), 465–470. https://doi.org/10.1161/CIRCULATIONAHA.104.518449
Hadaya, J., & Ardell, J. L. (2020). Autonomic Modulation for Cardiovascular Disease. Frontiers in Physi-ology, 11. https://doi.org/10.3389/fphys.2020.617459
Idris Fadul, A. A., Osman Mohamed, A. A., Mohammed Ahmed, A. A. S., Elmobark, S., Merghani Ham-mour, A. S., Elgaleel Khir Elsiad, N. M. N., & Mohammed Elhaj, E. A. (2025). Post-coronavirus Disease 2019 (COVID-19) Cardiovascular Manifestations: A Systematic Review of Long-Term Risks and Outcomes. Cureus. https://doi.org/10.7759/cureus.83083
ISAK, International Society For The Advancement Of Kinanthropometry. (2001). International Stand-ards for Anthropometric Assessment.
Jacob, G., Diedrich, L., Sato, K., Brychta, R. J., Raj, S. R., Robertson, D., Biaggioni, I., & Diedrich, A. (2019). Vagal and Sympathetic Function in Neuropathic Postural Tachycardia Syndrome. Hypertension, 73(5), 1087–1096. https://doi.org/10.1161/hypertensionaha.118.11803
Jagannatha, G. N. P., Yasmin, A. A. A. D. A., Pradnyana, I. W. A. S., Kamardi, S., Pradnyaandara, I. G. B. M. A., Pangkahila, E. E., Perkasa, G. O. B. D., & Wibawa, I. B. S. (2023). Therapeutic target and clini-cal impact of day-to-day blood pressure variability in hypertensive patients with covid-19. Hy-pertension Research, 46(1), 165–174. https://doi.org/10.1038/s41440-022-01077-x
Magagnin, V., Bassani, T., Bari, V., Turiel, M., Maestri, R., Pinna, G. D., & Porta, A. (2011). Non-stationarities significantly distort short-term spectral, symbolic and entropy heart rate variabil-ity indices. Physiological Measurement, 32(11), 1775–1786. https://doi.org/10.1088/0967-3334/32/11/S05
Mäkikallio, T. H., Huikuri, H. V., Mäkikallio, A., Sourander, L. B., Mitrani, R. D., Castellanos, A., & My-erburg, R. J. (2001). Prediction of sudden cardiac death by fractal analysis of heart rate variabil-ity in elderly subjects. Journal of the American College of Cardiology, 37(5), 1395–1402. https://doi.org/10.1016/s0735-1097(01)01171-8
Malliani, A., Pagani, M., & Lombardi, F. (1991). Neurovegetative regulation and cardiovascular diseases. Annali Italiani Di Medicina Interna, 6(4 Pt 2), 460–469.
Montano, N., Ruscone, T. G., Porta, A., Lombardi, F., Pagani, M., & Malliani, A. (1994). Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation, 90(4), 1826–1831. https://doi.org/10.1161/01.CIR.90.4.1826
Nam, J.-H., Park, J. I., Kim, B.-J., Kim, H.-T., Lee, J.-H., Lee, C.-H., Son, J.-W., Kim, U., Park, J.-S., Shin, D.-G., Hong, K. S., Jang, J. G., Ahn, J. H., Jin, H. J., Choi, E. Y., Shin, K.-C., Chung, J. H., Lee, K. H., Hur, J., … Lee, C.-K. (2021). Clinical impact of blood pressure variability in patients with COVID-19 and hypertension. Blood Pressure Monitoring, 26(5), 348–356. https://doi.org/10.1097/MBP.0000000000000544
Parati, G. (2005). Blood pressure variability: Its measurement and significance in hypertension. Journal of Hypertension, 23, S19. https://doi.org/10.1097/01.hjh.0000165624.79933.d3
Penteado, D. (s. d.). CardioSeries (Versão v2.4) [Programa de computador]. http://www.danielpenteado.com
Philbois, S. V., Facioli, T. P., De Lucca, I., Veiga, A. C., Chinellato, N., Simões, M. V., Tank, J., & Souza, H. C. D. (2024). What do we know about the role of menopause in cardiovascular autonomic regula-tion in hypertensive women? Menopause. https://doi.org/10.1097/GME.0000000000002348
Pollock, M. L., & Jackson, A. S. (1984). Research progress in validation of clinical methods of assessing body composition. Medicine and Science in Sports and Exercise, 16(6), 606–615.
Porta, A., Guzzetti, S., Montano, N., Furlan, R., Pagani, M., Malliani, A., & Cerutti, S. (2001). Entropy, en-tropy rate, and pattern classification as tools to typify complexity in short heart period variabil-ity series. IEEE Transactions on Biomedical Engineering, 48(11), 1282–1291. https://doi.org/10.1109/10.959324
Rafanelli, M., Walsh, K., Hamdan, M. H., & Buyan-Dent, L. (2019). Autonomic dysfunction: Diagnosis and management. Em Handbook of Clinical Neurology (V. 167, p. 123–137). Elsevier. https://doi.org/10.1016/B978-0-12-804766-8.00008-X
Shaffer, F., & Ginsberg, J. P. (2017). An Overview of Heart Rate Variability Metrics and Norms. Frontiers in Public Health, 5, 258. https://doi.org/10.3389/fpubh.2017.00258
Sheffield, L. T., & Roitman, D. (1976). Stress testing methodology. Progress in Cardiovascular Diseases, 19(1), 33–49. https://doi.org/10.1016/0033-0620(76)90007-4
Silva, L. E. V., Silva, C. A. A., Salgado, H. C., & Fazan, R. (2017). The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics. American Journal of Physiology-Heart and Circu-latory Physiology, 312(3), H469–H477. https://doi.org/10.1152/ajpheart.00507.2016
Siri, W. E. (1993). Body composition from fluid spaces and density: Analysis of methods. Nutrition, 9(5), 480–492.
Srivastava, P., Nabeel, P. M., Raj, K. V., Soneja, M., Chandran, D. S., Joseph, J., Wig, N., Jaryal, A. K., Thijssen, D., & Deepak, K. K. (2023). Baroreflex sensitivity is impaired in survivors of mild COVID‐19 at 3–6 months of clinical recovery; association with carotid artery stiffness. Physiological Re-ports, 11(21), e15845. https://doi.org/10.14814/phy2.15845
Tarvainen, M. P., Niskanen, J.-P., Lipponen, J. A., Ranta-aho, P. O., & Karjalainen, P. A. (2014). Kubios HRV – Heart rate variability analysis software. Computer Methods and Programs in Biomedicine, 113(1), 210–220. https://doi.org/10.1016/j.cmpb.2013.07.024
TASK FORCE, T. F. O. T. E. S. O. C. T. N. A. (1996). Heart Rate Variability: Standards of Measurement, Physiological Interpretation, and Clinical Use. Circulation, 93(5), 1043–1065. https://doi.org/10.1161/01.CIR.93.5.1043
Thayer, J. F., Yamamoto, S. S., & Brosschot, J. F. (2010). The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. International Journal of Cardiology, 141(2), 122–131. https://doi.org/10.1016/j.ijcard.2009.09.543
Wehrwein, E. A., Orer, H. S., & Barman, S. M. (2016). Overview of the Anatomy, Physiology, and Phar-macology of the Autonomic Nervous System. Em Comprehensive Physiology (p. 1239–1278). John Wiley & Sons, Ltd. https://doi.org/10.1002/cphy.c150037
Yachou, Y., El Idrissi, A., Belapasov, V., & Ait Benali, S. (2020). Neuroinvasion, neurotropic, and neuroin-flammatory events of SARS-CoV-2: Understanding the neurological manifestations in COVID-19 patients. Neurological Sciences, 41(10), 2657–2669. https://doi.org/10.1007/s10072-020-04575-3
Zhang, Y., Critchley, L. A., Tam, Y. H., & Tomlinson, B. (2004). Short-term postural reflexes in diabetic patients with autonomic dysfunction. Diabetologia, 47(2), 304–311. https://doi.org/10.1007/s00125-003-1286-2
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Ana Catarine Veiga, Naiara Chinellato, Luiza Correia Gimenez, Bruno Augusto Aguilar, João Vitor Martins Bernal, Stella Vieira Philbois, Tabata de Paula Facioli, Hugo Celso Dutra de Souza
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and ensure the magazine the right to be the first publication of the work as licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of authorship of the work and the initial publication in this magazine.
- Authors can establish separate additional agreements for non-exclusive distribution of the version of the work published in the journal (eg, to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Is allowed and authors are encouraged to disseminate their work electronically (eg, in institutional repositories or on their own website) prior to and during the submission process, as it can lead to productive exchanges, as well as to a subpoena more Early and more of published work (See The Effect of Open Access) (in English).
This journal provides immediate open access to its content (BOAI, http://legacy.earlham.edu/~peters/fos/boaifaq.htm#openaccess) on the principle that making research freely available to the public supports a greater global exchange of knowledge. The authors may download the papers from the journal website, or will be provided with the PDF version of the article via e-mail.
