{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:52:14Z","timestamp":1758405134411,"version":"3.41.2"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010580","name":"Department of Science and Technology, Hubei Provincial People's Government","doi-asserted-by":"publisher","award":["2020FCA014","2021CFB809"],"award-info":[{"award-number":["2020FCA014","2021CFB809"]}],"id":[{"id":"10.13039\/501100010580","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Previous studies suggest that autonomic dysfunction is associated with disease severity in acute phase in patients with coronavirus disease 2019 (COVID-19). However, the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 is unknown. We conducted a prospective study to investigate the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 discharged for 6 months. We included 40 eligible participants and collected the following indicators: heart rate variability (HRV), pulmonary function tests (PFTs), lung X-ray computed tomography (CT), routine blood parameters, liver function parameters, and lymphocyte subsets. We found that at 6 months post-discharge, HRV still had a tight correlation with pulmonary fibrosis. There was a significant difference in HRV between patients with and without diffusion dysfunction, but HRV did not differ between patients with or without ventilatory dysfunction. Diffusion dysfunction and pulmonary fibrosis were tightly associated, and HRV index changes in patients with diffusion dysfunction had the same trend as that of patients with pulmonary fibrosis. They had a lower standard deviation of NN intervals (SDNN), the standard deviation of the average NN intervals (SDANN), and the triangular index, but a higher ratio between LF and HF power (LF\/HF). In addition, WBC, neutrophils, and CD4\/CD8 were correlated with pulmonary fibrosis and HRV. We concluded that autonomic dysfunction is closely associated with pulmonary fibrosis and diffusion dysfunction, and immune mechanisms may potentially contribute to this process.<\/jats:p>","DOI":"10.3389\/fphys.2021.805925","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T07:47:36Z","timestamp":1642751256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Alternation of the Autonomic Nervous System Is Associated With Pulmonary Sequelae in Patients With COVID-19 After Six Months of Discharge"],"prefix":"10.3389","volume":"12","author":[{"given":"Tao","family":"Bai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feierkaiti","family":"Yushanjiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongke","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghuang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianchu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohua","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanling","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/cc8132","article-title":"Clinical review: a review and analysis of heart rate variability and the diagnosis and prognosis of infection.","volume":"13","author":"Ahmad","year":"2009","journal-title":"Crit. Care"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.573718","article-title":"Applications of non-invasive neuromodulation for the management of disorders related to COVID-19.","volume":"11","author":"Baptista","year":"2020","journal-title":"Front. Neurol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93546-5","article-title":"Clinical characterization of dysautonomia in long COVID-19 patients.","volume":"11","author":"Barizien","year":"2021","journal-title":"Sci. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1097\/SHK.0000000000001192","article-title":"Heart rate variability, clinical and laboratory measures to predict future deterioration in patients presenting with sepsis.","volume":"51","author":"Barnaby","year":"2019","journal-title":"Shock"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.5665\/sleep.3230","article-title":"Circadian variation of heart rate variability across sleep stages.","volume":"36","author":"Boudreau","year":"2013","journal-title":"Sleep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1016\/j.jiph.2020.07.001","article-title":"Immune response in COVID-19: a review.","volume":"13","author":"Chowdhury","year":"2020","journal-title":"J. Infect. Public Health"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1164\/rccm.201710-1981ST","article-title":"Recommendations for a standardized pulmonary function report. an official american thoracic society technical statement.","volume":"196","author":"Culver","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/j.1365-2796.2004.01442.x","article-title":"Autonomic neural regulation of immunity.","volume":"257","author":"Czura","year":"2005","journal-title":"J. Intern. Med."},{"key":"B9","doi-asserted-by":"publisher","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. (Lond.)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.561749","article-title":"Potential role of autonomic dysfunction in Covid-19 morbidity and mortality.","volume":"11","author":"Del Rio","year":"2020","journal-title":"Front. Physiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.mayocp.2018.04.009","article-title":"Pulmonary function tests for the generalist: a brief review.","volume":"93","author":"Dempsey","year":"2018","journal-title":"Mayo Clin. Proc."},{"key":"B12","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1001\/jama.2017.21907","article-title":"Acute respiratory distress syndrome: advances in diagnosis and treatment.","volume":"319","author":"Fan","year":"2018","journal-title":"JAMA"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1159\/000518141","article-title":"Six-Month pulmonary impairment after severe COVID-19: a prospective, multicentre follow-up study.","volume":"100","author":"Faverio","year":"2021","journal-title":"Respiration"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1093\/milmed\/usaa405","article-title":"Heart rate variability as a possible predictive marker for acute inflammatory response in COVID-19 patients.","volume":"186","author":"Hasty","year":"2021","journal-title":"Mil. Med"},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1097\/CM9.0000000000000819","article-title":"Diagnosis and treatment protocol for novel coronavirus pneumonia (Trial Version 7).","volume":"133","author":"Jing-Ya","year":"2020","journal-title":"Chin. Med. J. (Engl)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1002\/cphy.c130051","article-title":"Autonomic nervous system and immune system interactions.","volume":"4","author":"Kenney","year":"2014","journal-title":"Compr. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ana.25807","article-title":"COVID-19: a global threat to the nervous system.","volume":"88","author":"Koralnik","year":"2020","journal-title":"Ann. Neurol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0125-2019","article-title":"The supportive care needs of people living with pulmonary fibrosis and their caregivers: a systematic review.","volume":"29","author":"Lee","year":"2020","journal-title":"Eur. Respir Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1080\/22221751.2020.1825914","article-title":"Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.","volume":"9","author":"Leung","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101079","article-title":"COVID-19 and the effects on pulmonary function following infection: a retrospective analysis.","volume":"39","author":"Lewis","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1097\/JCN.0000000000000817","article-title":"ActiGraph and short-term heart rate variability study protocol: amended for the COVID-19 pandemic.","volume":"36","author":"Luong","year":"2021","journal-title":"J. Cardiovasc. Nurs"},{"key":"B23","doi-asserted-by":"publisher","first-page":"L257","DOI":"10.1152\/ajplung.00238.2020","article-title":"Healing after COVID-19: are survivors at risk for pulmonary fibrosis?","volume":"320","author":"McDonald","year":"2021","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00779","article-title":"Heart Rate Variability (HRV) and Pulse Rate Variability (PRV) for the assessment of autonomic responses.","volume":"11","author":"Mejia-Mejia","year":"2020","journal-title":"Front. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1080\/17476348.2017.1312346","article-title":"Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis.","volume":"11","author":"Meyer","year":"2017","journal-title":"Expert Rev. Respir Med."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-020-00363-7","article-title":"Assessment of physiological signs associated with COVID-19 measured using wearable devices.","volume":"3","author":"Natarajan","year":"2020","journal-title":"NPJ Digit. Med."},{"journal-title":"National Health Commission of the People\u2019s Reupblic of China","article-title":"Handbook of prevention and treatment of the pneumonia caused by the Novel Coronavirus (2019-nCoV),","year":"2020","key":"B27"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.630038","article-title":"Alteration of autonomic nervous system is associated with severity and outcomes in patients with COVID-19.","volume":"12","author":"Pan","year":"2021","journal-title":"Front. Physiol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/2021.07.02.21259891","article-title":"Heart rate variability as a prospective predictor of early COVID-19 symptoms.","author":"Ponomarev","year":"2021","journal-title":"medRxiv [Preprint]"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur. Respiratory J."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.arbres.2021.08.014","article-title":"Lung function, radiological findings and biomarkers of fibrogenesis in a cohort of COVID-19 patients six months after hospital discharge.","author":"Safont","year":"2021","journal-title":"Arch. Bronconeumol. (Engl. Ed) [Online ahead of print]"},{"key":"B32","doi-asserted-by":"publisher","first-page":"343","DOI":"10.3109\/10253890.2015.1045868","article-title":"Autonomic dysfunction and heart rate variability in depression.","volume":"18","author":"Sgoifo","year":"2015","journal-title":"Stress"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2017.00258","article-title":"An overview of heart rate variability metrics and norms.","volume":"5","author":"Shaffer","year":"2017","journal-title":"Front. Public Health"},{"key":"B34","doi-asserted-by":"publisher","first-page":"00243","DOI":"10.1183\/23120541.00243-2021","article-title":"Changes in pulmonary function and patient-reported outcomes during COVID-19 recovery: a longitudinal, prospective cohort study.","volume":"7","author":"Shah","year":"2021","journal-title":"ERJ Open Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.smrv.2011.02.005","article-title":"Heart rate variability, sleep and sleep disorders.","volume":"16","author":"Stein","year":"2012","journal-title":"Sleep Med. Rev."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2020.198197","article-title":"The role of dysregulated immune responses in COVID-19 pathogenesis.","volume":"290","author":"Tahaghoghi-Hajghorbani","year":"2020","journal-title":"Virus Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev.med.55.091902.103810","article-title":"Mechanisms of pulmonary fibrosis.","volume":"55","author":"Thannickal","year":"2004","journal-title":"Annu. Rev. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrn2647","article-title":"Neural regulation of endocrine and autonomic stress responses.","volume":"10","author":"Ulrich-Lai","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.928996","article-title":"Long-Term respiratory and neurological sequelae of COVID-19.","volume":"26","author":"Wang","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"B40","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1001\/jama.2020.12839","article-title":"Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review.","volume":"324","author":"Wiersinga","year":"2020","journal-title":"JAMA"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01599-21","article-title":"Immunological profiling of COVID-19 patients with pulmonary sequelae.","volume":"12","author":"Wu","year":"2021","journal-title":"mBio"},{"key":"B42","doi-asserted-by":"publisher","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."},{"key":"B43","doi-asserted-by":"publisher","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"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.805925\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T07:47:38Z","timestamp":1642751258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.805925\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,21]]},"references-count":43,"alternative-id":["10.3389\/fphys.2021.805925"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.805925","relation":{},"ISSN":["1664-042X"],"issn-type":[{"type":"electronic","value":"1664-042X"}],"subject":[],"published":{"date-parts":[[2022,1,21]]},"article-number":"805925"}}