HEART Rate Variability Biofeedback for LOng COVID Dysautonomia (HEARTLOC): Results of a Feasibility Study

Sivan M., Mckeever V., Natt M., Newton J.

Iftekhar N., Sivan M.

A 33-year-old man was referred to our specialist clinic with a 6-month history of a rapid purple discolouration of his legs on standing; he reported that his legs would progressively feel heavy, tingly, itchy, and become dusky in colour. Additionally, he said a petechial rash would occasionally appear over his feet (figure). The patient said his legs would return to their usual colour and the other symptoms would abate if he lay down.

Isaac R.O., Corrado J., Sivan M.

Introduction: A likely mechanism of Long COVID (LC) is dysautonomia, manifesting as orthostatic intolerance (OI). In our LC service, all patients underwent a National Aeronautics and Space Administration (NASA) Lean Test (NLT), which can detect OI syndromes of Postural Tachycardia Syndrome (PoTS) or Orthostatic Hypotension (OH) in a clinic setting. Patients also completed the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), a validated LC outcome measure. Our objectives in this retrospective study were (1) to report on the findings of the NLT; and (2) to compare findings from the NLT with LC symptoms reported on the C19-YRS. Methods: NLT data, including maximum heart rate increase, blood pressure decrease, number of minutes completed and symptoms experienced during the NLT were extracted retrospectively, together with palpitation and dizziness scores from the C19-YRS. Mann-Witney U tests were used to examine for statistical difference in palpitation or dizziness scores between patients with normal NLT and those with abnormal NLT. Spearman’s rank was used to examine the correlation between the degree of postural HR and BP change with C19-YRS symptom severity score. Results: Of the 100 patients with LC recruited, 38 experienced symptoms of OI during the NLT; 13 met the haemodynamic screening criteria for PoTS and 9 for OH. On the C19-YRS, 81 reported dizziness as at least a mild problem, and 68 for palpitations being at least a mild problem. There was no significant statistical difference between reported dizziness or palpitation scores in those with normal NLT and those with abnormal NLT. The correlation between symptom severity score and NLT findings was <0.16 (poor). Conclusions: We have found evidence of OI, both symptomatically and haemodynamically in patients with LC. The severity of palpitations and dizziness reported on the C19-YRS does not appear to correlate with NLT findings. We would recommend using the NLT in all LC patients in a clinic setting, regardless of presenting LC symptoms, due to this inconsistency.

Corrado J., Halpin S., Preston N., Whiteside D., Tarrant R., Davison J., Simms A.D., O'Connor R.J., Casson A., Sivan M.

IntroductionLong COVID (LC), also known as post-COVID-19 syndrome, refers to symptoms persisting 12 weeks after COVID-19 infection. It affects up to one in seven people contracting the illness and causes a wide range of symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. Many of these symptoms can be linked to dysautonomia or dysregulation of the autonomic nervous system after SARS-CoV2 infection. This study aims to test the feasibility and estimate the efficacy, of the heart rate variability biofeedback (HRV-B) technique via a standardised slow diaphragmatic breathing programme in individuals with LC.Methods and analysis30 adult LC patients with symptoms of palpitations or dizziness and an abnormal NASA Lean Test will be selected from a specialist Long COVID rehabilitation service. They will undergo a 4-week HRV-B intervention using a Polar chest strap device linked to the Elite HRV phone application while undertaking the breathing exercise technique for two 10 min periods everyday for at least 5 days a week. Quantitative data will be gathered during the study period using: HRV data from the chest strap and wrist-worn Fitbit, the modified COVID-19 Yorkshire Rehabilitation Scale, Composite Autonomic Symptom Score, WHO Disability Assessment Schedule and EQ-5D-5L health-related quality of life measures. Qualitative feedback on user experience and feasibility of using the technology in a home setting will also be gathered. Standard statistical tests for correlation and significant difference will be used to analyse the quantitate data.Ethics and disseminationThe study has received ethical approval from Health Research Authority (HRA) Leicester South Research Ethics Committee (21/EM/0271). Dissemination plans include academic and lay publications.Trial registration numberNCT05228665.

Larsen N.W., Stiles L.E., Shaik R., Schneider L., Muppidi S., Tsui C.T., Geng L.N., Bonilla H., Miglis M.G.

BackgroundAutonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.ObjectiveTo assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.DesignCross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.Participants2,413 adults ages 18–64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.Main measuresThe main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.Key resultsSixty-six percent of PASC patients had a COMPASS-31 score &gt;20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].ConclusionsEvidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.

Greenhalgh T., Sivan M., Delaney B., Evans R., Milne R.

### What you need to know This article updates and extends a previous BMJ Practice Pointer published in August 2020 when almost no peer reviewed research or evidence based guidance on the condition was available.1 In this update we outline how clinicians might respond to the questions that patients ask. The term “long covid”2 refers to prolonged symptoms following infection with SARS-CoV-2 that are not explained by an alternative diagnosis. It embraces the National Institute for Health and Care Excellence (NICE)’s terms “ongoing symptomatic covid-19” (symptoms lasting 4-12 weeks) and “post covid-19 syndrome” (symptoms beyond 12 weeks),3 the US Centers for Disease Control and Prevention’s group of “post-covid conditions,”4 and the World Health Organization’s “post covid-19 condition.”5 In mid-2022, approximately 70% of the UK adult population had been infected with SARS-CoV-2.6 Of these, almost 2 million report covid-19 symptoms persisting for more than four weeks; 807 000 (41% of all people with long covid) for more than a year; and 403 000 (19%) for more than two years.7 Based on workforce data from the British Medical Association,8 a full time equivalent general practitioner with an average list size (approximately 2000) has around 65 patients with long covid, 27 of whom will have been unwell for more than a year, and 12 for more than two years. Most general practices have far fewer patients with a long covid diagnostic code on their electronic health record9 for a combination of reasons, including lack of presentation, lack of recognition, and inadequate coding. These figures do not cover children, who are outside the …

Sivan M., Corrado J., Mathias C.

Autonomic dysfunction is an increasingly recognised complication in chronic neurological conditions such as Parkinson’s disease, and other medical conditions, including diabetes mellitus, chronic fatigue syndrome, postural tachycardia syndrome (PoTS) with and without Ehlers-Danlos syndrome, fibromyalgia and recently Long COVID. Despite laboratory-based tests to evaluate normal and abnormal autonomic function, there are no home-based tests to record neuro-cardiovascular autonomic responses to common stimuli in daily life that are dependent on normal functioning of the autonomic nervous system. We have developed an adapted blood pressure/heart rate Autonomic Profile (aAP) that can be used by an individual independently and repeatedly in a domiciliary setting to determine the physiological and symptomatic response to standing, food, and physical or mental (cognitive, emotional) activities. The aAP aids separating autonomic failure (often irreversible) from autonomic dysfunction. This helps the individual and attending healthcare professional understand the relationship between symptoms and common triggers in daily life and informs on self-management in debilitating conditions such as the postural tachycardia syndrome (PoTS) and Long Covid.

Sivan M., Preston N., Parkin A., Makower S., Gee J., Ross D., Tarrant R., Davison J., Halpin S., O'Connor R.J., Horton M.

Background The C19-YRS is the literature's first condition-specific, validated scale for patient assessment and monitoring in Post-COVID-19 syndrome (PCS). The 22-item scale's subscales (scores) are symptom severity (0–100), functional disability (0–50), additional symptoms (0–60), and overall health (0–10). Objectives This study aimed to test the scale's psychometric properties using Rasch analysis and modify the scale based on analysis findings, emerging information on essential PCS symptoms, and feedback from a working group of patients and professionals. Methods Data from 370 PCS patients were assessed using a Rasch Measurement Theory framework to test model fit, local dependency, response category functioning, differential item functioning, targeting, reliability, and unidimensionality. The working group undertook iterative changes to the scale based on the psychometric results and including essential symptoms. Results Symptom severity and functional disability subscales showed good targeting and reliability. Post hoc rescoring suggested that a 4-point response category structure would be more appropriate than an 11-point response for both subscales. Symptoms with binary responses were placed in the other symptoms subscale. The overall health single-item subscale remained unchanged. Conclusion A 17-item C19-YRSm was developed with subscales (scores): symptom severity (0–30), functional disability (0–15), other symptoms (0–25), and overall health (0–10).

Carmona-Torre F., Mínguez-Olaondo A., López-Bravo A., Tijero B., Grozeva V., Walcker M., Azkune-Galparsoro H., López de Munain A., Alcaide A.B., Quiroga J., del Pozo J.L., Gómez-Esteban J.C.

IntroductionOn March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.ObjectiveTo conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.ResultsAutonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.ConclusionSymptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.

O'Connor R.J., Preston N., Parkin A., Makower S., Ross D., Gee J., Halpin S.J., Horton M., Sivan M.

As our understanding of the nature and prevalence of post-coronavirus disease 2019 (COVID-19) syndrome (PCS) is increasing, a measure of the impact of COVID-19 could provide valuable insights into patients' perceptions in clinical trials and epidemiological studies as well as routine clinical practice. To evaluate the clinical usefulness and psychometric properties of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) in patients with PCS, a prospective, observational study of 187 consecutive patients attending a post-COVID-19 rehabilitation clinic was conducted. The C19-YRS was used to record patients' symptoms, functioning, and disability. A global health question was used to measure the overall impact of PCS on health. Classical psychometric methods (data quality, scaling assumptions, targeting, reliability, and validity) were used to assess the C19-YRS. For the total group, missing data were low, scaling and targeting assumptions were satisfied, and internal consistency was high (Cronbach's α = 0.891). Relationships between the overall perception of health and patients' reports of symptoms, functioning, and disability demonstrated good concordance. This is the first study to examine the psychometric properties of an outcome measure in patients with PCS. In this sample of patients, the C19-YRS was clinically useful and satisfied standard psychometric criteria, providing preliminary evidence of its suitability as a measure of PCS.

Fournié C., Chouchou F., Dalleau G., Caderby T., Cabrera Q., Verkindt C.

• Heart rate variability biofeedback is increasingly used to manage chronic symptoms. • Psychological and physiological effects of HRVB have been reported in several studies. • Results showed regulatory effects on autonomic function and clinical symptoms. • HRVB could assist in the management of chronic patients. Heart rate variability biofeedback (HRVB) is a non-pharmacological intervention used in the management of chronic diseases. A systematic search was performed according to eligibility criteria including adult chronic patients, HRVB as main treatment with or without control conditions, and psychophysiological outcomes as dependent variables. In total, 29 articles were included. Reported results showed the feasibility of HRVB in chronic patients without adverse effects. Significant positive effects were found in various patient profiles on hypertension and cardiovascular prognosis, inflammatory state, asthma disorders, depression and anxiety, sleep disturbances, cognitive performance and pain, which could be associated with improved quality of life. Improvements in clinical outcomes co-occurred with improvements in heart rate variability, suggesting possible regulatory effect of HRVB on autonomic function. HRVB could be effective in managing patients with chronic diseases. Further investigations are required to confirm these results and recommend the most effective method.

Crook H., Raza S., Nowell J., Young M., Edison P.

Abstract Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.

Shouman K., Vanichkachorn G., Cheshire W.P., Suarez M.D., Shelly S., Lamotte G.J., Sandroni P., Benarroch E.E., Berini S.E., Cutsforth-Gregory J.K., Coon E.A., Mauermann M.L., Low P.A., Singer W.

Post-COVID-19 syndrome is a poorly understood aspect of the current pandemic, with clinical features that overlap with symptoms of autonomic/small fiber dysfunction. An early systematic analysis of autonomic dysfunction following COVID-19 is lacking and may provide initial insights into the spectrum of this condition. We conducted a retrospective review of all patients with confirmed history of COVID-19 infection referred for autonomic testing for symptoms concerning for para-/postinfectious autonomic dysfunction at Mayo Clinic Rochester or Jacksonville between March 2020 and January 2021. We identified 27 patients fulfilling the search criteria. Symptoms developed between 0 and 122 days following the acute infection and included lightheadedness (93%), orthostatic headache (22%), syncope (11%), hyperhidrosis (11%), and burning pain (11%). Sudomotor function was abnormal in 36%, cardiovagal function in 27%, and cardiovascular adrenergic function in 7%. The most common clinical scenario was orthostatic symptoms without tachycardia or hypotension (41%); 22% of patients fulfilled the criteria for postural tachycardia syndrome (POTS), and 11% had borderline findings to support orthostatic intolerance. One patient each was diagnosed with autoimmune autonomic ganglionopathy, inappropriate sinus tachycardia, vasodepressor syncope, cough/vasovagal syncope, exacerbation of preexisting orthostatic hypotension, exacerbation of sensory and autonomic neuropathy, and exacerbation of small fiber neuropathy. Abnormalities on autonomic testing were seen in the majority of patients but were mild in most cases. The most common finding was orthostatic intolerance, often without objective hemodynamic abnormalities on testing. Unmasking/exacerbation of preexisting conditions was seen. The temporal association between infection and autonomic symptoms implies a causal relationship, which however cannot be proven by this study.

Sivan M., Halpin S., Gees J., Makower S., Parkin A., Ross D., Horton M., O'Connor R.

Dani M., Dirksen A., Taraborrelli P., Torocastro M., Panagopoulos D., Sutton R., Lim P.B.

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.

Hurt R.T., Ganesh R., Schroeder D.R., Hanson J.L., Fokken S.C., Overgaard J.D., Bauer B.A., Thilagar B.P., Aakre C.A., Pruthi S., Croghan I.T.

Objective: This study evaluated the feasibility and satisfaction of using a wearable brain activity sensing device for stress reduction among patients experiencing Long COVID (LC). Patients and Methods: Patients with LC (N = 45) were invited to participate in an open-label pilot study. Participants were asked to use a brain-sensing electroencephalogram (S-EEG) wearable device (Muse-S™) daily for 90 days and followed for an additional 90 days (180 days total participation). Study enrollment began June 28, 2022, and ended July 28, 2023. Results: Patients were predominantly female (82%), white (96%), and with an average age of 47.6 (±12.5) years. At the end of treatment (90 days), cognition, sleep, self-efficacy, and quality-of-life quality of life improved ( P  < .001 to P  = .04). In addition, stress and anxiety were significantly reduced ( P  < .001). These significant changes persisted by end-of-study (180 days). For stress ( P  = .023) and anxiety ( P  = .033), a change from the baseline during follow-up was significantly associated with the amount of S-EEG usage. The end-of-study satisfaction survey indicated that patients were very satisfied with the S-EEG device, and 97% planned to continue using it. Conclusion: Results suggest that the S-EEG device improved cognition in LC, which is one of the main severe symptoms we see in our LC clinic. In addition, it helped reduce stress and anxiety. These findings have important clinical implications for LC patients using S-EEG as an adjunct to concurrent LC clinical care which includes pharmacotherapies.

Saunders E.G., Pouliopoulou D.V., Miller E., Billias N., MacDermid J.C., Brunton L., Pereira T.V., Quinn K.L., Bobos P.

ObjectiveSeveral rehabilitation interventions have been proposed to support people with post-COVID-19 condition (PCC). However, the full spectrum of these interventions remains unclear, partly due to the complexity of PCC, which encompasses a broad range of symptoms affecting multiple organ systems and health domains. This scoping review aimed to identify the available rehabilitation interventions for PCC and the outcome measures used to evaluate them, to facilitate the development of multifaceted interventions and improve patient care.MethodsFollowing the Joanna Briggs Institute Framework, we searched CINAHL, EMBASE, MEDLINE, PsychINFO, CENTRAL and Scopus databases from inception to 22 January 2024 for experimental and observational studies investigating rehabilitation interventions for adults with PCC. Interventions and their corresponding outcome measures were synthesised based on targeted outcomes aligned with the most common manifestations of PCC. The quality of intervention reporting was assessed using the Template for Intervention Description and Replication (TIDieR) checklist.ResultsWe identified 74 studies; 28 randomised trials (37.8%) and 46 observational and quasi-experimental designs (62.2%). Most interventions consisted of different combinations of education, exercises and therapies to manage dyspnoea, fatigue and psychological symptoms, such as anxiety and depression. Few studies addressed postexertional malaise, cognitive function, memory, balance and coordination. At least half of the included studies required a confirmed SARS-CoV-2 infection for participant inclusion. Reporting on adherence rates was limited, and 65% of the studies did not report adverse events.ConclusionThere is a need for more comprehensive and inclusive approaches that address the full spectrum of PCC symptomatology to improve patient care and enhance the reproducibility of future studies.

Godfrey B., Shardha J., Witton S., Bodey R., Tarrant R., Greenwood D.C., Sivan M.

Background: Post-COVID-19 Syndrome or long COVID (LC) is a novel public health crisis and, when persistent (>2 years), is a long-term condition. Post-exertional symptom exacerbation (PESE) is a characteristic symptom of LC and can be improved in a structured pacing rehabilitation programme. Aims: To evaluate the effect of an 8-week structured World Health Organisation (WHO) Borg CR-10 pacing protocol on PESE episodes, LC symptoms, and quality of life in a cohort of individuals with long-term LC. Methods: Participants received weekly telephone calls with a clinician to discuss their activity phase, considering their PESE symptoms that week. They completed the Leeds PESE questionnaire (LPQ), C19-YRS (Yorkshire Rehabilitation Scale), and EQ-5D-5L at the beginning of the programme (0 weeks), the end of programme (8 weeks), and at final follow-up (12 weeks). Results: Thirty-one participants (duration of LC symptoms: 29 months) completed the programme. The PESE episodes decreased in number each week (15% fewer each week, 95% CI: 11% to 20%, p < 0.001) and were of shorter duration and milder severity each week. The changes in C19YRS symptom severity and functional disability (0–12 weeks) were statistically significant but not clinically significant. The EQ5D-5L index score change was not statistically significant. Conclusions: A structured pacing protocol effectively reduced PESE episode frequency, duration, and severity but did not produce clinically significant changes in LC symptoms, reflecting the long-term nature of the condition in this cohort.

Treadwell J.R., Wagner J., Reston J.T., Phillips T., Hedden-Gross A., Tipton K.N.

For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies. We first interviewed 11 stakeholders (clinicians, clinician/researchers, payors, patient advocates) to gain clinical insights and identify key areas of focus. We searched Embase, CINAHL, Medline, PsycINFO, and PubMed databases for relevant English-language articles published between 1 January 2020 and 30 April 2024. We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform). All information was summarized narratively. We included 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine + famotidine, maraviroc + pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a nutraceutical (SIM01) on fatigue and gastrointestinal upset. The 11 guidelines and position statements addressed numerous aspects of treatment, but primarily exercise/rehabilitation, fluid/salt intake, and the use of compression garments. The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin. Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management.

Steere K.

Purpose: Heart rate variability (HRV) has been used for decades as a tool for measuring systemic health through the autonomic nervous system (ANS). The purpose of this paper was to examine the literature on HRV and to investigate its use in the long COVID (LC) population. Summary of Key Points: Measurement devices vary significantly in their validity and reliability when compared with the gold standard of electrocardiogram (ECG). Wrist and hand devices typically demonstrate diminished validity for capturing HRV signal, while chest strap devices often exhibit high reliability and validity. Lack of transparency in third-party software used to clean and analyze HRV data makes assessment for accuracy problematic. This is of particular concern when single beat miscalculations can result in significantly dissimilar output. The conditions under which HRV data are collected, such as natural or paced breathing, activity intensity, and patient position, can dramatically affect HRV readings. While some individual HRV metrics have consistently been shown to reflect certain components of the ANS, such as high-frequency power as a measure of parasympathetic function, the meaning of other metrics is less clear. Recommendations for Clinical Practice: Heart rate variability can be an extraordinarily valuable tool to measure systemic function. However, it is recommended that clinicians be judicious in the interpretation of HRV, considering inconsistencies in presentation. This is particularly true in LC, where individual HRV varies greatly. In all populations, clinicians should consider using valid devices to assess trends in HRV values over time, along with consideration of unique physical conditions.

Mauro M., Zulian E., Bestiaco N., Polano M., Larese Filon F.

Background: Many COVID-19 survivors still experience long-term effects of an acute infection, most often characterised by neurological, cognitive and psychiatric sequelae. The treatment of this condition is challenging, and many hypotheses have been proposed. Non-invasive vagus nerve stimulation using slow-paced breathing (SPB) could stimulate both central nervous system areas and parasympathetic autonomic pathways, leading to neuromodulation and a reduction in inflammation. The aim of the present study was to evaluate physical, cognitive, emotional symptoms, executive functions and autonomic cardiac modulation after one month of at-home slow breathing intervention. Methods: 6655 healthcare workers (HCWs) were contacted via a company email in November 2022, of which N = 58 HCWs were enrolled as long COVID (cases) and N = 53 HCWs as controls. A baseline comparison of the two groups was performed. Subsequently each case was instructed on how to perform a resonant SPB using visual heart rate variability (HRV) biofeedback. They were then given a mobile video tutorial breathing protocol and asked to perform it three times a day (morning, early afternoon and before sleep). N = 33 cases completed the FU. At T0 and T1, each subject underwent COVID-related, psychosomatic and dysfunctional breathing questionnaires coupled with heart rate variability and manual dexterity assessments. Results: After one month of home intervention, an overall improvement in long-COVID symptoms was observed: confusion/cognitive impairment, chest pain, asthenia, headache and dizziness decreased significantly, while only a small increase in manual dexterity was found, and no relevant changes in cardiac parasympathetic modulation were observed.

Krishna B.A., Metaxaki M., Sithole N., Landín P., Martín P., Salinas-Botrán A.

Cardiovascular complications of COVID-19 are numerous and aspects of this phenomenon are not well known. The main objective of this manuscript is a systematic review of the acute and chronic cardiovascular complications secondary to COVID-19.

Polizzi J., Tosto-Mancuso J., Tabacof L., Wood J., Putrino D.

IntroductionLong COVID involves debilitating symptoms, many of which mirror those observed with dysautonomia, and care must be taken with rehabilitation for autonomic dysfunction to avoid post-exertional malaise/post-exertional symptom exacerbation. Resonant breathing (breathing slowly at a defined rate of breaths per minute) requires less exertion and can potentially improve autonomic function. The objective of this work was to report on the impact of a resonant breathing program on self-reported symptoms and wellbeing in people with Long COVID.MethodsA retrospective analysis of de-identified data was completed in a convenience sample of people with Long COVID, who participated in the Meo Health (formerly known as Stasis HP) resonant breathing program. Participants completed baseline and follow up surveys.ResultsData were available for 99 participants. Most measures of symptoms and wellbeing improved at follow up, with the largest differences per participant seen in sense of wellness (47.3%, p &lt; 0.0001), ability to focus (57.5%, p &lt; 0.0001), ability to breathe (47.5%, p &lt; 0.0001), ability to control stress (61.8%, p &lt; 0.0001) and sleep quality (34.9%, p = 0.0002). Most (92%) participants reported improvement at follow up on the Patient Global Impression of Change Scale.ConclusionSelf-reported symptoms and wellbeing improved in people with Long COVID completing resonant breathing. Resonant breathing can be considered as an option within the broader treatment plan of people with Long COVID.

Polizzi J., Tosto-Mancuso J., Tabacof L., Wood J., Putrino D.

AbstractIntroductionLong COVID involves debilitating symptoms, many of which mirror those observed with dysautonomia, and care must be taken with traditional autonomic rehabilitation to avoid post-exertional malaise/post-exertional symptom exacerbation. Resonant breathing exercises require less exertion and can potentially improve autonomic function. The objective of this work was to report on the impact of a resonant breathing program on self-reported symptoms and wellbeing in people with Long COVID.MethodsA retrospective analysis of de-identified data was completed in a convenience sample of people with Long Covid, who participated in the Meo Health (formerly known as Stasis HP) resonant breathing program. Participants completed baseline and follow up surveys.ResultsData were available for 99 participants. Most measures of symptoms and wellbeing improved at follow up, with the largest differences per participant seen in sense of wellness (47.3%, p<0.0001), ability to focus (57.5%, p<0.0001), ability to breathe (47.5%, p<0.0001), ability to control stress (61.8%, p<0.0001) and sleep quality (34.9%, p=0.0002). Most (92%) participants reported improvement at follow up on the Patient Global Impression of Change Scale.ConclusionSelf-reported symptoms and wellbeing improved in people with Long COVID completing resonant breathing. Resonant breathing can be considered as an option within the broader treatment plan of people with Long COVID.

Tsampasian V., Bäck M., Bernardi M., Cavarretta E., Dębski M., Gati S., Hansen D., Kränkel N., Koskinas K., Niebauer J., Spadafora L., Frias Vargas M., Biondi-Zoccai G., Vassiliou V.S.

Abstract Aims Long COVID syndrome has had a major impact on million patients’ lives worldwide. The cardiovascular system is an important aspect of this multifaceted disease that may manifest in many ways. We have hereby performed a narrative review in order to identify the extent of the cardiovascular manifestations of the Long COVID syndrome. Methods and results An in-depth systematic search of the literature has been conducted for this narrative review. The systematic search of PubMed and Cochrane databases yielded 3993 articles, of which 629 underwent full-text screening. A total of 78 studies were included in the final qualitative synthesis and data evaluation. The pathophysiology of the cardiovascular sequelae of Long COVID syndrome and the cardiac manifestations and complications of Long COVID syndrome are critically evaluated. In addition, potential cardiovascular risk factors are assessed, and preventive methods and treatment options are examined in this review. Conclusion This systematic review poignantly summarizes the evidence from the available literature regarding the cardiovascular manifestations of Long COVID syndrome and reviews potential mechanistic pathways, diagnostic approaches, preventive measures, and treatment options.