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      Reduction of Cardiac Autonomic Modulation and Increased Sympathetic Activity by Heart Rate Variability in Patients With Long COVID

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          Abstract

          Although several clinical manifestations of persistent long coronavirus disease (COVID-19) have been documented, their effects on the cardiovascular and autonomic nervous system over the long term remain unclear. Thus, we examined the presence of alterations in cardiac autonomic functioning in individuals with long-term manifestations. The study was conducted from October 2020 to May 2021, and an autonomic assessment was performed to collect heart rate data for the heart rate variability (HRV) analysis. The study participants were divided into the long COVID clinical group, the intragroup, which included patients who were hospitalized, and those who were not hospitalized and were symptomatic for different periods (≤3, >3, ≤6, and >6 months), with and without dyspnoea. The control group, the intergroup, comprised of COVID-free individuals. Our results demonstrated that the long COVID clinical group showed reduced HRV compared with the COVID-19-uninfected control group. Patients aged 23–59 years developed COVID symptoms within 30 days after infection, whose diagnosis was confirmed by serologic or reverse-transcription polymerase chain reaction (swab) tests, were included in the study. A total of 155 patients with long COVID [95 women (61.29%), mean age 43.88 ± 10.88 years and 60 men (38.71%), mean age 43.93 ± 10.11 years] and 94 controls [61 women (64.89%), mean age 40.83 ± 6.31 and 33 men (35.11%), mean age 40.69 ± 6.35 years] were included. The intragroup and intergroup comparisons revealed a reduction in global HRV, increased sympathetic modulation influence, and a decrease in parasympathetic modulation in long COVID. The intragroup showed normal sympathovagal balance, while the intergroup showed reduced sympathovagal balance. Our findings indicate that long COVID leads to sympathetic excitation influence and parasympathetic reduction. The excitation can increase the heart rate and blood pressure and predispose to cardiovascular complications. Short-term HRV analysis showed good reproducibility to verify the cardiac autonomic involvement.

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          Most cited references33

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          Persistent Symptoms in Patients After Acute COVID-19

          This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.
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            High-dimensional characterization of post-acute sequalae of COVID-19

            The acute clinical manifestations of COVID-19 have been well characterized1,2, but the post-acute sequelae of this disease have not been comprehensively described. Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequelae-including diagnoses, medication use and laboratory abnormalities-in patients with COVID-19 who survived for at least 30 days after diagnosis. We show that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems. Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID-19 infection (that is, whether patients were not hospitalized, hospitalized or admitted to intensive care). Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID-19. These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID-19.
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              Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies

              The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. ‘Post-acute COVID’ (known colloquially as ‘long COVID’) is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of ‘long COVID’, and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.
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                Author and article information

                Contributors
                URI : http://loop.frontiersin.org/people/383537/overview
                URI : http://loop.frontiersin.org/people/1647624/overview
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                29 April 2022
                2022
                29 April 2022
                : 9
                : 862001
                Affiliations
                [1] 1Postgraduate Program in Parasitic Biology in the Amazon, Laboratory of Infectious and Cardiopulmonary Diseases, Long COVID Program, Centre for Biological and Health Sciences, Pará State University , Belém, Brazil
                [2] 2Laboratory of Infectious and Cardiopulmonary Diseases, Long COVID Program, Centre for Biological and Health Sciences, Pará State University , Belém, Brazil
                [3] 3Department of Human Movement Sciences, Centre for Biological and Health Sciences, Pará State University , Belém, Brazil
                [4] 4Centre for Biological and Health Sciences, Pará State University , Belém, Brazil
                Author notes

                Edited by: Lucas Liaudet, Centre Hospitalier Universitaire Vaudois (CHUV), Switzerland

                Reviewed by: Giuseppe Mascia, San Martino Hospital (IRCCS), Italy; J. Derek Kingsley, Kent State University, United States

                *Correspondence: Luiz Fábio Magno Falcão fabiofalcao@ 123456uepa.br

                This article was submitted to General Cardiovascular Medicine, a section of the journal Frontiers in Cardiovascular Medicine

                †These authors have contributed equally to this work

                Article
                10.3389/fcvm.2022.862001
                9098798
                35571200
                b02daba5-625c-4a42-8dbf-cdd0f6b447e1
                Copyright © 2022 Marques, Silva, Trindade, Santos, Rocha, Vasconcelos, Quaresma and Falcão.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 January 2022
                : 04 April 2022
                Page count
                Figures: 1, Tables: 5, Equations: 2, References: 36, Pages: 10, Words: 7527
                Funding
                Funded by: Fundação Amazônia Paraense de Amparo à Pesquisa, doi 10.13039/501100005288;
                Funded by: Secretaría de Estado de Ciencia, Tecnología e Innovación, doi 10.13039/501100010567;
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, doi 10.13039/501100002322;
                Funded by: Universidade Federal do Pará, doi 10.13039/501100007382;
                Categories
                Cardiovascular Medicine
                Original Research

                autonomic nervous system,coronavirus infection,long covid,heart rate,heart rate variability

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