{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:30:06Z","timestamp":1772253006198,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VieCuri Corona Foundation and Regio Noord-Limburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>The persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and the number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10 s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101\u2013141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.<\/jats:p>","DOI":"10.3390\/s23052473","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T04:32:33Z","timestamp":1677126753000},"page":"2473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Association of Heart Rate Variability with Pulmonary Function Impairment and Symptomatology Post-COVID-19 Hospitalization"],"prefix":"10.3390","volume":"23","author":[{"given":"Estelle A. M. C.","family":"Adang","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7116-4465","authenticated-orcid":false,"given":"Maud T. A.","family":"Strous","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"}]},{"given":"Joop P.","family":"van den Bergh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"},{"name":"NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"}]},{"given":"Debbie","family":"Gach","sequence":"additional","affiliation":[{"name":"NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Clinical Epidemiology, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"}]},{"given":"Vivian E. M.","family":"van Kampen","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"}]},{"given":"Roel E. P.","family":"van Zeeland","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7185-9491","authenticated-orcid":false,"given":"Dennis G.","family":"Barten","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"}]},{"given":"Frits H. M.","family":"van Osch","sequence":"additional","affiliation":[{"name":"NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Clinical Epidemiology, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands"},{"name":"Department of Epidemiology, Maastricht University, 6229 ER Maastricht, The Netherlands"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022, June 01). WHO Coronavirus Disease (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1016\/S1473-3099(21)00703-9","article-title":"A clinical case definition of post-COVID-19 condition by a Delphi consensus","volume":"22","author":"Soriano","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101019","DOI":"10.1016\/j.eclinm.2021.101019","article-title":"Characterizing long COVID in an international cohort: 7 months of symptoms and their impact","volume":"38","author":"Davis","year":"2021","journal-title":"Eclinicalmedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0140-6736(20)32656-8","article-title":"6-month consequences of COVID-19 in patients discharged from hospital: A cohort study","volume":"397","author":"Huang","year":"2021","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2003276","DOI":"10.1183\/13993003.03276-2020","article-title":"Patient-reported outcome measures after COVID-19: A prospective cohort study","volume":"56","author":"Wong","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106453","DOI":"10.1016\/j.rmed.2021.106453","article-title":"Clinical outcomes and quality of life of COVID-19 survivors: A follow-up of 3 months post hospital discharge","volume":"184","author":"Todt","year":"2021","journal-title":"Respir. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/jmv.27309","article-title":"Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)\u2014A systematic review and meta-analysis","volume":"94","author":"Malik","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/S2213-2600(21)00383-0","article-title":"Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): A UK multicentre, prospective cohort study","volume":"9","author":"Evans","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_9","first-page":"21259277","article-title":"Risk Factors for Long COVID: Analyses of 10 Longitudinal Studies and Electronic Health Records in the UK","volume":"2021","author":"Thompson","year":"2021","journal-title":"medRxiv"},{"key":"ref_10","first-page":"21259452","article-title":"Persistent symptoms following SARS-CoV-2 in-fection in a random community sample of 508,707 people","volume":"2021","author":"Whitaker","year":"2021","journal-title":"medRxiv"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.cmi.2021.05.033","article-title":"Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients","volume":"27","author":"Peghin","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.7861\/clinmed.2020-0896","article-title":"Autonomic dysfunction in \u2018long COVID\u2019: Rationale, physiology and management strategies","volume":"21","author":"Dani","year":"2021","journal-title":"Clin. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.1113\/JP271539","article-title":"Anti-inflammatory properties of the vagus nerve: Potential therapeutic implications of vagus nerve stimulation","volume":"594","author":"Bonaz","year":"2016","journal-title":"J. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1126\/science.1209985","article-title":"Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit","volume":"334","author":"Olofsson","year":"2011","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1600-065X.2012.01138.x","article-title":"Rethinking inflammation: Neural circuits in the regulation of immunity","volume":"248","author":"Olofsson","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jneuroim.2013.04.011","article-title":"Vagal nerve activity as a moderator of brain\u2013immune relationships","volume":"260","author":"Ohira","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2003677","DOI":"10.1183\/13993003.03677-2020","article-title":"Diffusion Capacity Abnormalities for Carbon Monoxide in Patients with COVID-19 At Three-Month Follow-up","volume":"58","author":"Qin","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3233\/ADR-200273","article-title":"The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer\u2019s Disease and Aging: A Review of Knowledge","volume":"4","author":"Rangon","year":"2020","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s11239-021-02549-6","article-title":"Autonomic dysfunction in SARS-CoV-2 infection acute and long-term implications COVID-19 editor\u2019s page series","volume":"52","author":"Becker","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Acanfora, D., Nolano, M., Acanfora, C., Colella, C., Provitera, V., Caporaso, G., Rodolico, G.R., Bortone, A.S., Galasso, G., and Casucci, G. (2022). Impaired Vagal Activity in Long-COVID-19 Patients. Viruses, 14.","DOI":"10.3390\/v14051035"},{"key":"ref_21","unstructured":"(2022, June 01). EurekAlert! Pilot Study Suggests Long COVID Could Be Linked to The Effects of SARS-CoV-2 on The Vagus Nerve. Available online: http:\/\/www.eurekalert.org\/news-releases\/943102."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1247","DOI":"10.1016\/S2214-109X(22)00286-8","article-title":"Post-COVID-19 condition 3 months after hospitalisation with SARS-CoV-2 in South Africa: A prospective cohort study","volume":"10","author":"Dryden","year":"2022","journal-title":"Lancet Glob. Health"},{"key":"ref_23","unstructured":"WHO (2022, June 01). Global COVID-19 Clinical Platform: Rapid Core Case Report Form (CRF). Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-Clinical_CRF-2020.4."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2101499","DOI":"10.1183\/13993003.01499-2021","article-title":"ERS\/ATS technical standard on interpretive strategies for routine lung function tests","volume":"60","author":"Stanojevic","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.7453\/gahmj.2014.073","article-title":"Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health Risk","volume":"4","author":"Mccraty","year":"2015","journal-title":"Glob. Adv. Health Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Vollmer, M. (2015, January 6\u20139). Robust, Simple and Reliable Measure of Heart Rate Variability using Relative RR Intervals. Proceedings of the Computing in Cardiology Conference, Nice, France.","DOI":"10.1109\/CIC.2015.7410984"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1542-474X.2011.00417.x","article-title":"Reliability of Ultra-Short ECG Indices for Heart Rate Variability","volume":"16","author":"Nussinovitch","year":"2011","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mol, M.B.A., Strous, M.T.A., van Osch, F.H.M., Vogelaar, F.J., Barten, D.G., Farchi, M., Foudraine, N.A., and Gidron, Y. (2021). Heart-rate-variability (HRV), predicts outcomes in COVID-19. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0258841"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Munoz, M.L., van Roon, A., Riese, H., Thio, C., Oostenbroek, E., Westrik, I., de Geus, E.J.C., Gansevoort, R., Lefrandt, J., and Nolte, I.M. (2015). Validity of (Ultra-)Short Recordings for Heart Rate Variability Measurements. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138921"},{"key":"ref_30","first-page":"8S13","article-title":"Physiological aspects of the decline of pulmonary function with age","volume":"21","author":"Rouatbi","year":"2004","journal-title":"Rev. des Mal. Respir."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1183\/20734735.000318","article-title":"Sex differences in respiratory function","volume":"14","author":"LoMauro","year":"2018","journal-title":"Breathe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1164\/rccm.200208-876OC","article-title":"Sex Differences in Thoracic Dimensions and Configuration","volume":"168","author":"Bellemare","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.neubiorev.2016.03.007","article-title":"Sex differences in healthy human heart rate variability: A meta-analysis","volume":"64","author":"Koenig","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100463","DOI":"10.1016\/j.eclinm.2020.100463","article-title":"Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery","volume":"25","author":"Zhao","year":"2020","journal-title":"Eclinicalmedicine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S2213-2600(21)00174-0","article-title":"3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: A prospective study","volume":"9","author":"Wu","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2003481","DOI":"10.1183\/13993003.03481-2020","article-title":"Cardiopulmonary recovery after COVID-19: An observational prospective multicentre trial","volume":"57","author":"Sonnweber","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.arbres.2021.01.036","article-title":"Lung Function sequelae in COVID-19 Patients 3 Months After Hospital Discharge","volume":"57","author":"Sibila","year":"2021","journal-title":"Arch. Bronconeumol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2003448","DOI":"10.1183\/13993003.03448-2020","article-title":"Dyspnoea, lung function and CT findings 3 months after hospital admission for COVID-19","volume":"57","author":"Lerum","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3\u201395-yr age range: The global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1016\/S0735-1097(21)04417-X","article-title":"Heart rate variability is reduced 3- AND 6-months after hospitalization for COVID-19 infection","volume":"77","author":"Adler","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bai, T., Zhou, D., Yushanjiang, F., Wang, D., Zhang, D., Liu, X., Song, J., Zhang, J., Hou, X., and Ma, Y. (2021). Alternation of the Autonomic Nervous System Is Associated With Pulmonary Sequelae in Patients With COVID-19 After Six Months of Discharge. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.805925"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1046\/j.0954-6820.2003.01250.x","article-title":"Heart rate variability in long-term risk assessment in middle-aged women with coronary heart disease: The Stockholm Female Coronary Risk Study","volume":"255","author":"Janszky","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ipej.2022.01.004","article-title":"Heart rate variability as a marker of cardiovascular dysautonomia in post-COVID-19 syndrome using artificial intelligence","volume":"22","author":"Shah","year":"2022","journal-title":"Indian Pacing Electrophysiol. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"862001","DOI":"10.3389\/fcvm.2022.862001","article-title":"Reduction of Cardiac Autonomic Modulation and Increased Sympathetic Activity by Heart Rate Variability in Patients With Long COVID","volume":"9","author":"Marques","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.pcad.2012.09.001","article-title":"Heart Rate Variability Today","volume":"55","author":"Xhyheri","year":"2012","journal-title":"Prog. Cardiovasc. Dis."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/23\/5\/2473\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:40:22Z","timestamp":1760121622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/23\/5\/2473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,23]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["s23052473"],"URL":"https:\/\/doi.org\/10.3390\/s23052473","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202212.0410.v1","asserted-by":"object"}]},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,23]]}}}