Cardiovascular and autonomic dysfunction in long-COVID syndrome and the potential role of non-invasive therapeutic strategies on cardiovascular outcomes

A significant percentage of COVID-19 survivors develop long-lasting cardiovascular sequelae linked to autonomic nervous system dysfunction, including fatigue, arrhythmias, and hypertension. This post-COVID-19 cardiovascular syndrome is one facet of “long-COVID,” generally defined as long-term health problems persisting/appearing after the typical recovery period of COVID-19. Despite the fact that this syndrome is not fully understood, it is urgent to develop strategies for diagnosing/managing long-COVID due to the immense potential for future disease burden. New diagnostic/therapeutic tools should provide health personnel with the ability to manage the consequences of long-COVID and preserve/improve patient quality of life. It has been shown that cardiovascular rehabilitation programs (CRPs) stimulate the parasympathetic nervous system, improve cardiorespiratory fitness (CRF), and reduce cardiovascular risk factors, hospitalization rates, and cognitive impairment in patients suffering from cardiovascular diseases. Given their efficacy in improving patient outcomes, CRPs may have salutary potential for the treatment of cardiovascular sequelae of long-COVID. Indeed, there are several public and private initiatives testing the potential of CRPs in treating fatigue and dysautonomia in long-COVID subjects. The application of these established rehabilitation techniques to COVID-19 cardiovascular syndrome represents a promising approach to improving functional capacity and quality of life. In this brief review, we will focus on the long-lasting cardiovascular and autonomic sequelae occurring after COVID-19 infection, as well as exploring the potential of classic and novel CRPs for managing COVID-19 cardiovascular syndrome. Finally, we expect this review will encourage health care professionals and private/public health organizations to evaluate/implement non-invasive techniques for the management of COVID-19 cardiovascular sequalae.

[1]  G. Buonocore,et al.  Pediatric Multisystem Syndrome Associated with SARS-CoV-2 (MIS-C): The Interplay of Oxidative Stress and Inflammation , 2022, International journal of molecular sciences.

[2]  C. Yasuda,et al.  Morphological, cellular, and molecular basis of brain infection in COVID-19 patients , 2022, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Couzin-Frankel.  Clues to long COVID , 2022, Science.

[4]  Kana Kazawa,et al.  [A tele-nursing program for elderly with lifestyle-related chronic diseases during the COVID-19 pandemic in a municipality: an implementation report]. , 2022, [Nihon koshu eisei zasshi] Japanese journal of public health.

[5]  Maria Papadopoulou,et al.  Autonomic dysfunction in long-COVID syndrome: a neurophysiological and neurosonology study , 2022, Journal of Neurology.

[6]  A. Marques,et al.  Inpatient rehabilitation of a person with Guillain-Barré syndrome associated with COVID-19 infection: An expert interdisciplinary approach to a case study. , 2022, Physiotherapy theory and practice.

[7]  R. Mungmunpuntipantip,et al.  Guillain-Barré syndrome amid the coronavirus disease 2019 era. , 2022, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[8]  A. Boner,et al.  Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome. , 2022, Allergy and asthma proceedings.

[9]  H. Tilg,et al.  Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases , 2022, Gastroenterology.

[10]  H. Makhlouf,et al.  Prevalence and patterns of symptoms of dysautonomia in patients with long‐COVID syndrome: A cross‐sectional study , 2022, Annals of clinical and translational neurology.

[11]  J. Finsterer.  Small fiber neuropathy underlying dysautonomia in COVID‐19 and in post‐SARS‐CoV‐2 vaccination and long‐COVID syndromes , 2022, Muscle & nerve.

[12]  R. Klein.  Mechanisms of coronavirus infectious disease 2019-related neurologic diseases , 2022, Current opinion in neurology.

[13]  M. Merad,et al.  The immunology and immunopathology of COVID-19 , 2022, Science.

[14]  F. Molinari,et al.  Heart rate variability for medical decision support systems: A review , 2022, Comput. Biol. Medicine.

[15]  Matthew W. Martinez,et al.  2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play , 2022, Journal of the American College of Cardiology.

[16]  Reed J. D. Sorensen,et al.  Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21 , 2022, The Lancet.

[17]  M. Supervia,et al.  Impacto de la pandemia por COVID-19 en los Servicios de Rehabilitación de España , 2022, Rehabilitación.

[18]  F. Kakamad,et al.  Post COVID-19 neurological complications; a meta-analysis , 2022, Annals of Medicine and Surgery.

[19]  C. Tomczak,et al.  Autonomic cardiovascular reflex control of hemodynamics during exercise in heart failure with reduced ejection fraction and the effects of exercise training. , 2022, Reviews in cardiovascular medicine.

[20]  Benjamin Bowe,et al.  Long-term cardiovascular outcomes of COVID-19 , 2022, Nature Medicine.

[21]  Y. Shoenfeld,et al.  The autonomic aspects of the post-COVID19 syndrome , 2022, Autoimmunity Reviews.

[22]  V. Chaturvedi,et al.  Heart rate variability as a marker of cardiovascular dysautonomia in post-COVID-19 syndrome using artificial intelligence , 2022, Indian Pacing and Electrophysiology Journal.

[23]  Teresa Bernardo,et al.  Occurrence of Guillain-Barre Syndrome During the Initial Symptomatic Phase of COVID-19 Disease: Coincidence or Consequence? , 2021, Cureus.

[24]  L. Benedetti,et al.  The importance of thinking about Guillain-Barré syndrome during the COVID-19 pandemic: a case with pure dysautonomic presentation , 2021, Journal of NeuroVirology.

[25]  G. Di Sante,et al.  Evidence of lung perfusion defects and ongoing inflammation in an adolescent with post-acute sequelae of SARS-CoV-2 infection , 2021, The Lancet Child & Adolescent Health.

[26]  P. Edison,et al.  Long covid—mechanisms, risk factors, and management , 2021, BMJ.

[27]  J. Anaya,et al.  Post-COVID syndrome. A case series and comprehensive review , 2021, Autoimmunity Reviews.

[28]  Ryan J. Low,et al.  Characterizing long COVID in an international cohort: 7 months of symptoms and their impact , 2021, EClinicalMedicine.

[29]  L. Hajjar,et al.  Effects of inspiratory muscle training combined with aerobic exercise training on neurovascular control in chronic heart failure patients , 2021, ESC heart failure.

[30]  S. Kent,et al.  Immunological dysfunction persists for 8 months following initial mild-moderate SARS-CoV-2 infection , 2021, medRxiv.

[31]  J. Courel-Ibáñez,et al.  Post-COVID-19 Syndrome and the Potential Benefits of Exercise , 2021, International journal of environmental research and public health.

[32]  D. Brodie,et al.  Post-acute COVID-19 syndrome , 2021, Nature Medicine.

[33]  John Mwangi,et al.  Long COVID, a comprehensive systematic scoping review , 2021, Infection.

[34]  D. Altmann,et al.  Decoding the unknowns in long covid , 2021, BMJ.

[35]  Benjamin Bowe,et al.  High-dimensional characterization of post-acute sequelae of COVID-19 , 2021, Nature.

[36]  Jeremy S. Brown,et al.  ‘Long-COVID’: a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19 , 2020, Thorax.

[37]  T. Foiadelli,et al.  SARS-CoV-2 infection in pediatric population , 2020, Acta bio-medica : Atenei Parmensis.

[38]  N. Nabavi.  Long covid: How to define it and how to manage it , 2020, BMJ.

[39]  L. Ferrucci,et al.  A public health perspective of aging: do hyper-inflammatory syndromes such as COVID-19, SARS, ARDS, cytokine storm syndrome, and post-ICU syndrome accelerate short- and long-term inflammaging? , 2020, Immunity & Ageing.

[40]  Angelo Carfì,et al.  Persistent Symptoms in Patients After Acute COVID-19. , 2020, JAMA.

[41]  H. Krumholz,et al.  Extrapulmonary manifestations of COVID-19 , 2020, Nature Medicine.

[42]  P. Theocharis,et al.  Hyperinflammatory shock in children during COVID-19 pandemic , 2020, The Lancet.

[43]  G. Lippi,et al.  Poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19): Pooled analysis of early reports , 2020, Journal of Critical Care.

[44]  D. Forman,et al.  Never Too Old for Cardiac Rehabilitation. , 2019, Clinics in geriatric medicine.

[45]  K. Stanford,et al.  Effects of Exercise to Improve Cardiovascular Health , 2019, Front. Cardiovasc. Med..

[46]  U. Rajendra Acharya,et al.  Deep learning for healthcare applications based on physiological signals: A review , 2018, Comput. Methods Programs Biomed..

[47]  M. Al-mallah,et al.  Cardiorespiratory Fitness and Cardiovascular Disease Prevention: an Update , 2018, Current Atherosclerosis Reports.

[48]  B. Matata,et al.  A Review of Interventions to Improve Enrolment and Adherence to Cardiac Rehabilitation Among Patients Aged 65 Years or Above , 2017, Current cardiology reviews.

[49]  L. Vianna,et al.  Acute and Chronic Effects of Isometric Handgrip Exercise on Cardiovascular Variables in Hypertensive Patients: A Systematic Review , 2017, Sports.

[50]  D. Bonaduce,et al.  Effects of exercise training on cardiovascular adrenergic system , 2013, Front. Physiol..

[51]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[52]  Academisch Proefschrift,et al.  The interplay of oxidative stress and inflammation in atherosclerosis: an epidemiologic approach , 2010 .

[53]  Jennifer L. Dorosz.  Updates in cardiac rehabilitation. , 2009, Physical medicine and rehabilitation clinics of North America.

[54]  Yasuo Ohashi,et al.  Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. , 2009, JAMA.

[55]  F. Schmidt.  Meta-Analysis , 2008 .

[56]  Pedagógia,et al.  Cross Sectional Study , 2019 .

[57]  P. Mueller,et al.  EXERCISE TRAINING AND SYMPATHETIC NERVOUS SYSTEM ACTIVITY: EVIDENCE FOR PHYSICAL ACTIVITY DEPENDENT NEURAL PLASTICITY , 2007, Clinical and experimental pharmacology & physiology.

[58]  U. Rajendra Acharya,et al.  Heart rate variability: a review , 2006, Medical and Biological Engineering and Computing.

[59]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[60]  K. Johnson.  An Update. , 1984, Journal of food protection.