A Case Report on Heart Rate Variability Biofeedback and Postconcussion Syndrome: Healing the Autonomic Nervous System

Postconcussion syndrome is a devastating condition of the mind, body, and even personality. Mounting research demonstrates that heart rate variability biofeedback can help the concussed individual in three critical ways: (a) eliciting high amplitude oscillations in cardiovascular functions and thereby strengthening self-regulatory control mechanisms;(b) restoring autonomic balance;and (c) increasing the afferent impulse stream from the baroreceptors to restore balance between inhibitory and excitatory processes in the brain.

Major Depressive Disorder and Chronic Fatigue Syndrome Show Characteristic Heart Rate Variability Profiles Reflecting Autonomic Dysregulations: Differentiation by Linear Discriminant Analysis.

Major depressive disorder (MDD) and chronic fatigue syndrome (CFS) have overlapping symptoms, and differentiation is important to administer the proper treatment. The present study aimed to assess the usefulness of heart rate variability (HRV) indices. Frequency-domain HRV indices, including high-frequency (HF) and low-frequency (LF) components, their sum (LF+HF), and their ratio (LF/HF), were measured in a three-behavioral-state paradigm composed of initial rest (Rest), task load (Task), and post-task rest (After) periods to examine autonomic regulation. It was found that HF was low at Rest in both disorders, but was lower in MDD than in CFS. LF and LF+HF at Rest were low only in MDD. Attenuated responses of LF, HF, LF+HF, and LF/HF to task load and an excessive increase in HF at After were found in both disorders. The results indicate that an overall HRV reduction at Rest may support a diagnosis of MDD. HF reduction was found in CFS, but with a lesser severity. Response disturbances of HRV to Task were observed in both disorders, and would suggest the presence of CFS when the baseline HRV has not been reduced. Linear discriminant analysis using HRV indices was able to differentiate MDD from CFS, with a sensitivity and specificity of 91.8% and 100%, respectively. HRV indices in MDD and CFS show both common and different profiles, and can be useful for the differential diagnosis.

Heart Rate Variability and Pregnancy Complications: Systematic Review.

BACKGROUND: The autonomic nervous system (ANS) is known as a critical regulatory system for pregnancy-induced adaptations. If it fails to function, life-threatening pregnancy complications could occur. Hence, understanding and monitoring the underlying mechanism of action for these complications are necessary. OBJECTIVE: We aimed to systematically review the literature concerned with the associations between heart rate variability (HRV), as an ANS biomarker, and pregnancy complications. METHODS: We performed a comprehensive search in the PubMed, Medline Completion, CINAHL Completion, Web of Science Core Collection Classic, Cochrane Library, and SCOPUS databases in February 2022 with no time span limitation. We included studies concerned with the association between any pregnancy complications and HRV, with or without a control group. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was used for the review of the studies, and Covidence software was used for the study selection process. For data synthesis, we used the guideline by Popay et al. RESULTS: Finally, 12 studies with 6656 participants were included. Despite the methodological divergency that hindered a comprehensive comparison, our findings suggest that ANS is linked with some common pregnancy complications including fetal growth. However, existing studies do not support an association between ANS and gestational diabetes mellitus. Studies that linked pulmonary and central nervous system disorders with ANS function did not provide enough evidence to draw conclusions. CONCLUSIONS: This review highlights the importance of understanding and monitoring the underlying mechanism of ANS in pregnancy-induced adaptations and the need for further research with robust methodology in this area.

Study of sympathetic skin response in patients with COVID-19 infection.

OBJECTIVES: Many articles hypothesized the potential role of autonomic nervous system in the pathogenesis and outcome of COVID-19 infection. Several studies reported both central and peripheral nervous system involvement in COVID-19 as well. Up to our knowledge, there is no study evaluating whether this virus could invade the autonomic nervous system affecting its function adversely. Sympathetic skin response (SSR) has long been used as a method of evaluating the autonomic nervous system. Regarding the importance of the autonomic nervous system in hemostasis and wide consequences of COVID-19 infection, we designed this study to evaluate the autonomic nervous system function in patients recovered from COVID-19 compared with normal population who are not yet infected by this virus by the means of SSR. METHODS: This case-control study included 70 patients surviving COVID-19 who met the inclusion and exclusion criteria that went under SSR. The data gathered were compared with those without the history of any symptoms attributable to COVID-19 during the pandemic. RESULTS: There was a correlation between COVID-19 infection and abnormal SSR (p value < 0.0001) with the most effect on the latency prolongation of the action potential recorded from the median nerve at palms (effect size: right: 3.90, left: 3.69). Moreover, the greater severity of the disease correlated with more abnormality of parameters recorded by SSR technique. CONCLUSIONS: Abnormal SSR parameters could be a good indicator of autonomic nervous system involvement in patients with COVID-19 infection. It might be a predictor of disease severity, clinical outcomes and prognosis as well.

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies.

A systematic review and meta-analysis of long COVID symptoms.

BACKGROUND: Ongoing symptoms or the development of new symptoms following a SARS-CoV-2 diagnosis has caused a complex clinical problem known as "long COVID" (LC). This has introduced further pressure on global healthcare systems as there appears to be a need for ongoing clinical management of these patients. LC personifies heterogeneous symptoms at varying frequencies. The most complex symptoms appear to be driven by the neurology and neuropsychiatry spheres. METHODS: A systematic protocol was developed, peer reviewed, and published in PROSPERO. The systematic review included publications from the 1st of December 2019-30th June 2021 published in English. Multiple electronic databases were used. The dataset has been analyzed using a random-effects model and a subgroup analysis based on geographical location. Prevalence and 95% confidence intervals (CIs) were established based on the data identified. RESULTS: Of the 302 studies, 49 met the inclusion criteria, although 36 studies were included in the meta-analysis. The 36 studies had a collective sample size of 11,598 LC patients. 18 of the 36 studies were designed as cohorts and the remainder were cross-sectional. Symptoms of mental health, gastrointestinal, cardiopulmonary, neurological, and pain were reported. CONCLUSIONS: The quality that differentiates this meta-analysis is that they are cohort and cross-sectional studies with follow-up. It is evident that there is limited knowledge available of LC and current clinical management strategies may be suboptimal as a result. Clinical practice improvements will require more comprehensive clinical research, enabling effective evidence-based approaches to better support patients.

Is the Effect of the COVID-19 Vaccine on Heart Rate Variability Permanent?

Background and Objectives: The risk of autonomic dysfunction with COVID-19 vaccines used worldwide in the COVID-19 pandemic remains a topic of debate. Heart rate variability has a number of parameters that can be used to assess autonomic nervous system dynamics. The aim of this study was to investigate the effect of a COVID-19 vaccine (Pfizer-BioNTech) on heart rate variability and autonomic nervous system parameters, and the duration of the effect. Materials and Methods: A total of 75 healthy individuals who visited an outpatient clinic to receive the COVID-19 vaccination were included in this prospective observational study. Heart rate variability parameters were measured before vaccination and on days 2 and 10 after vaccination. SDNN, rMSSD and pNN50 values were evaluated for time series analyses, and LF, HF, and LF/HV values for frequency-dependent analyses. Results: The SDNN and rMSDD values declined significantly on day 2 after vaccination, while the pNN50 and LF/HF values increased significantly on day 10. The values at pre-vaccination and at day 10 were comparable. The pNN50 and LF/HF values declined significantly on day 2 and increased significantly on day 10. The values at pre-vaccination and at day 10 were comparable. Conclusions: This study showed that the decline in HRV observed with COVID-19 vaccination was temporary, and that the Pfizer-BioNTech COVID-19 vaccination did not cause permanent autonomic dysfunction.

A Biological Approach to Building Resilience and Wellness Capacity Among Police Exposed to Posttraumatic Stress Injuries: Protocol for a Randomized Controlled Trial.

BACKGROUND: Law enforcement officers are routinely exposed to hazardous, disturbing events that can impose severe stress and long-term psychological trauma. As a result, police and other public safety personnel (PSP) are at increased risk of developing posttraumatic stress injuries (PTSIs) and disruptions to the autonomic nervous system (ANS). ANS functioning can be objectively and noninvasively measured by heart rate (HR), heart rate variability (HRV), and respiratory sinus arrhythmia (RSA). Traditional interventions aimed at building resilience among PSP have not adequately addressed the physiological ANS dysregulations that lead to mental and physical health conditions, as well as burnout and fatigue following potential psychological trauma. OBJECTIVE: In this study, we will investigate the efficacy of a web-based Autonomic Modulation Training (AMT) intervention on the following outcomes: (1) reducing self-reported symptoms of PTSI, (2) strengthening ANS physiological resilience and wellness capacity, and (3) exploring how sex and gender are related to baseline differences in psychological and biological PTSI symptoms and response to the AMT intervention. METHODS: The study is comprised of 2 phases. Phase 1 involves the development of the web-based AMT intervention, which includes 1 session of baseline survey measures, 6 weekly sessions that integrate HRV biofeedback (HRVBF) training with meta-cognitive skill practice, and 1 session of follow-up survey measures. Phase 2 will use a cluster randomized control design to test the effectiveness of AMT on the following prepost outcomes: (1) self-report symptoms of PTSI and other wellness measures; (2) physiological indicators of health and resilience including resting HR, HRV, and RSA; and (3) the influence of sex and gender on other outcomes. Participants will be recruited for an 8-week study across Canada in rolling cohorts. RESULTS: The study received grant funding in March 2020 and ethics approval in February 2021. Due to delays related to COVID-19, phase 1 was completed in December 2022, and phase 2 pilot testing began in February 2023. Cohorts of 10 participants in the experimental (AMT) and control (prepost assessment only) groups will continue until a total of 250 participants are tested. Data collection from all phases is expected to conclude in December 2025 but may be extended until the intended sample size is reached. Quantitative analyses of psychological and physiological data will be conducted in conjunction with expert coinvestigators. CONCLUSIONS: There is an urgent need to provide police and PSP with effective training that improves physical and psychological functioning. Given that help-seeking for PTSI is reduced among these occupational groups, AMT is a promising intervention that can be completed in the privacy of one's home. Importantly, AMT is a novel program that uniquely addresses the underlying physiological mechanisms that support resilience and wellness promotion and is tailored to the occupational demands of PSP. TRIAL REGISTRATION: ClinicalTrials.gov NCT05521360; https://clinicaltrials.gov/ct2/show/NCT05521360. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33492.

Impact of Covid-19 Infection on Baseline Autonomic Symptoms in Patients with Pre-Existing Postural Tachycardia Syndrome and Orthostatic Intolerance

Background: Recently there have been several published case series of some survivors of COVID-19 infection left with chronic symptoms of autonomic dysfunction (AD) with features of orthostatic tachycardia syndrome (POTS). However, the impact of this viral illness on the underlying autonomic symptoms has not been studied in the patient population who have a pre-existing POTS diagnosis and are receiving treatment. Objective(s): So far, the impact of this viral illness on the underlying autonomic symptoms has not been studied in patients with a pre-existing POTS diagnosis and receiving treatment. Our study aims to report the impact of a COVID-19 infection on these patient populations, both during the acute phase of the disease and post-recovery. Method(s): Our Institution Review Board (IRB) approval was obtained to access charts of the study subjects. Basic demographic and diagnosis details including the age, sex, prominent symptoms, duration of POTS diagnosis, medications, associated autonomic disease, and medication regimen were obtained from the retrospective chart review. Additional information regarding COVID-19 infection, course of illness, need for hospitalization, worsening of POTS symptoms, need for ED visits, improvement with the escalation of therapy, the type of persisting symptoms, and vaccination status were obtained from both chart review and details from the patients during the scheduled office visit. Result(s): A total of 49 patients were studied. About 42 patients (82 %) had the alpha-variant infection before the vaccines were available. 28% (14 patients) of them had tested positive for infection more than once (i.e infection with alpha, delta, or omicron variant). About 38 (92.7%) of them reported having worsening of their baseline POTS symptoms during the active infection phase. About 28 patients (57 %) experienced worsening of their dysautonomia symptoms for at least 1-6 months post-infection. Nearly 30 patients (73.2%) required additional therapy for their symptom control and improvement. Conclusion(s): Of subjects with pre-existing POTS, most experienced a worsening of their baseline autonomic symptoms after suffering the COVID-19 infection which required additional pharmacotherapy for their symptom improvement. The majority of them had recovered within 6 months of therapy. From our observation, it is evident that the COVID-19 infection exacerbates the underlying symptoms in patients with established POTS disease.Copyright © 2023

Autonomic Dysfunction after Covid-19 Immunization - Case Report

Background: The infection caused by the SARS-CoV-2 continues affecting millions of people worldwide and vaccines to prevent the coronavirus disease (COVID-19) are considered the most promising approach for curbing the pandemic. Otherwise, cardiovascular and neurological complications associated with the vaccines were speculated and some few case reports were published. Objective(s): We describe a case of postural orthostatic tachycardia syndrome (POTS) after viral vector COVID-19 vaccination and the possible autoimmune process of the syndrome. Method(s): A 35-year-old female, without previous symptoms or comorbidities, developed intermittent palpitation, intense fatigue and dyspnea, compromising her daily activities, triggered by upright position, seven days following the second dose of the Oxford vaccine. Physical examination was normal, except for a heart rate (HR) increase of 33 beats/min from supine to standing position, with no significant change in blood pressure and reproduction of symptoms. Result(s): A 24-hour Holter monitoring revealed episodes of spontaneous sinus tachycardia correlated with palpitation and fatigue. Extensive diagnostic investigations excluded primary cardiac, endocrine, infectious and rheumatologic etiologies. The patient underwent an autonomic function test which demonstrated normal baroreflex sensitivity, as well as normal cardiovagal and adrenergic scores. Head-up tilt test showed persistent orthostatic tachycardia (HR increase from a medium of 84 beats/min in supine position to 126 beats/min during upright tilt), without hypotension, consistent with the diagnostic criteria for POTS. According to the current guidelines, general behavior recommendations, pharmacotherapy with low dose of propranolol associated with the autonomic rehabilitation were oriented. Along three months of follow-up, the patient reported a gradually improvement in her symptoms. Conclusion(s): POTS is a heterogeneous disorder of the autonomic nervous system characterized by orthostatic tachycardia associated with symptoms of orthostatic intolerance. Although the physiopathology of COVID-19 vaccine and autonomic disorders remains speculative, autoimmune response is one of the possible mechanisms. Based on clinic presentation, the time frame of symptom onset is consistent with other well-known post-vaccination syndromes, which may be an indicator of an autoimmune process induced by immunization. Further studies are needed to assess causal relationship between immunization and autonomic dysfunction.Copyright © 2023

Ndegree35 - Neurophysiology solving the vomiting dilemma

Objectives: Post Covid severe vomiting together with proximal muscle weakness is a misleading combination, this describes a rare but definite clinical association between myasthenia gravis and autonomic failure and strengthen the concept that subacute autonomic neuropathy is an autoimmune disorder. Content: A 39 ys old adult female presented with postCovid severe vomiting for one year with 40 kgs loss Upper gastrointestinal endoscopy revealed gastric dilatation associated with eosophageal and gastric stasis and hypertrophic pyloric stenosis. the gastroenterologist sought neurological consultation for the coexisting unexplained limb weakness before operation EMG & NCV was all normal except instability of the MUAPs Slow rate Repetitive supramaximal stimulation (RNS) revealed significant decremental response with no significant high rate stimulation incrementation Chest CT revealed an anterior mediastinal mass Surprisingly, She had an old CT during the covid infection that showed the same mass. Thoracoscopic resection revealed type B1 thymoma Following tumor resection, the patient improved gradually, Few months later endoscopy revealed a normal stomach with strong peristaltic waves and the patient was symptom free Infections are recognized to trigger exacerbations and crisis in MG Dysautonomia is not a commonly recognized feature of myasthenia gravis, but there have been rare reports of myasthenia gravis coexisting with autonomic failure, usually in association with thymoma. The autonomic dysfunction can present as isolated gastroparesis these observations support a rare but definite clinical association between myasthenia gravis and autonomic failure Neurophysiology could reveal undiagnosed MG with thymoma causing autonomic dysfunction in the form of gastroparesis and agonizing vomiting. Keywords: Myasthenia gravis;Gastroparesis;Autonomic failure;Thymoma;PostCovid vomiting. French language not detected for EMBFRA articles source xmlCopyright © 2023

Complex breathlessness in postural tachycardia syndrome and autonomic dysfunction

Breathlessness can occur in a number of autonomic conditions, often in the form of dysfunctional breathing. The exact mechanism remains uncertain, but reduced perfusion of blood pressure receptors and chemoreceptors in the carotid sinus and carotid body, leading to hyperventilation, is postulated. This is recognised to occur in vasovagal syncope and in cases of significant autonomic dysfunction. It also occurs in PoTS, a condition predominantly affecting young women and often precipitated by another illness and increasingly by coronavirus disease 2019. It is characterised by cardiovascular and respiratory symptoms when upright, is relieved by recumbency and is associated with a significant heart rate increase. Other autonomic symptoms of organ dysfunction can occur, in the gastrointestinal and genitourinary system for example. There are guidelines and therapies that can produce significant symptomatic improvements, but maintaining a high level of suspicion for the diagnosis is important, as it can easily be overlooked.Copyright © ERS 2021.

Autoimmune Peripheral Neuropathies

Autoimmune peripheral neuropathies (APNs) occur when immunological tolerance to peripheral nerve components (myelin, axon, or ganglionic neurons) is lost. The most common APNs are acute inflammatory polyneuropathies, such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), immunoglobulin M (IgM)–anti–myelin-associated glycoprotein (MAG) antibody–mediated paraproteinemic neuropathy, and those caused by vasculitis or viral infections. Both cellular and humoral factors, either independently or in concert with each other, appear to play a role, but the specific immune mechanisms have not been fully elucidated. Infectious agents, such as Campylobacter jejuni and Zika virus via molecular mimicry, and now COVID-19, are implicated in some GBS subtypes, but the factors that break tolerance in the other APNs remain unknown. In some acute or chronic APN, antibodies against peripheral nerve glycolipids or glycoproteins are pathogenic and well characterized. Pathogenic IgG4 antibodies against antigens at the nodes of Ranvier that cause disadhesion of nodal and paranodal proteins and conduction block define distinct CIDP subtypes, which respond only to rituximab. Some newly emerging, not pathogenic, autoantibodies more commonly seen in small fiber sensory neuropathies and neuropathic pains are briefly discussed. The current immunotherapies in all APNs are described based on controlled trials or clinical experience. © 2023 Elsevier Ltd. All rights reserved.

The social representation and social action effect of critical issues: autonomic system and self-report measures

By combining words and images that impact emotions and generate empathetic storytelling, advertising (ADV) has evolved into a form of communication for promoting consumer awareness, positive social change, and ADV-related decisional processes, even on topics of high-social relevance such as crisis communication. This study explored consumers' emotional and cognitive responses to crisis-related ADVs using implicit (autonomic) and explicit (self-report) measurements. Nineteen participants watched twelve high-impact social communications about Covid-19, personal health, safety, and prosociality, while autonomic and self-report data were collected. Personal health, safety, and prosociality had higher skin conductance than Covid-19 stimuli, indicating higher arousal and engagement. Personal health reported lower heart rate variability values than Covid-19, suggesting greater emotional reactions for personal health topics, but also lesser mental load for Covid-19 stimuli. Self-report results confirmed autonomic findings. In conclusion, communications about personal health, safety, and prosociality generate higher emotional impact and allow for effective storytelling that facilitates viewer identification, developing a high level of empathy.

Functional features of the cardiovascular system in COVID-19 children

The functional state of the cardiovascular system of children aged 8-12 years who underwent COVID-19 was studied. It has been shown that one of the mechanisms of functional disorders in the cardiovascular system in the period from 3 to 6 months after suffering COVID-19 is considered a syndrome of autonomic dysfunction. The manifestations of autonomic dysfunction in children are hypertensive changes in the cardiovascular system in the absence of pronounced clinical manifestations, the presence of functional tension of regulatory systems, unsatisfactory functional status, decreased rates of increase in heart rate power in response to load, low values of sympathetic regulation mechanisms and centralization of the cardiovascular system regulation circuit, a large proportion of the influence of the peripheral regulation circuit. Conclusion. One of the pathogenetic mechanisms for reducing the functional parameters of the cardiovascular system in children who have had a coronavirus infection is endothelial dysfunction syndrome.

Cardiopulmonary testing in long COVID-19 versus non-COVID-19 patients with undifferentiated Dyspnea on exertion.

BACKGROUND: Dyspnea and fatigue are characteristics of long SARS-CoV-2 (COVID)-19. Cardiopulmonary exercise testing (CPET) can be used to better evaluate such patients. RESEARCH QUESTION: How significantly and by what mechanisms is exercise capacity impaired in patients with long COVID who are coming to a specialized clinic for evaluation? STUDY DESIGN AND METHODS: We performed a cohort study using the Mayo Clinic exercise testing database. Subjects included consecutive long COVID patients without prior history of heart or lung disease sent from the Post-COVID Care Clinic for CPET. They were compared to a historical group of non-COVID patients with undifferentiated dyspnea also without known cardiac or pulmonary disease. Statistical comparisons were performed by t-test or Pearson's chi2 test controlling for age, sex, and beta blocker use where appropriate. RESULTS: We found 77 patients with long COVID and 766 control patients. Long COVID patients were younger (47 ± 15 vs 50 ± 10 years, P < .01) and more likely female (70% vs 58%, P < .01). The most prominent difference on CPETs was lower percent predicted peak V̇O2 (73 ± 18 vs 85 ± 23%, p < .0001). Autonomic abnormalities (resting tachycardia, CNS changes, low systolic blood pressure) were seen during CPET more commonly in long COVID patients (34 vs 23%, P < .04), while mild pulmonary abnormalities (mild desaturation, limited breathing reserve, elevated V̇E/V̇CO2) during CPET were similar (19% in both groups) with only 1 long COVID patient showing severe impairment. INTERPRETATION: We identified severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Though mild pulmonary and autonomic impairment were common in long COVID patients, marked limitations were uncommon. We hope our observations help to untangle the physiologic abnormalities responsible for the symptomatology of long COVID.

What We Know Now About Long Covid Syndromes?

It is now widely accepted that SARS-CoV-2 infection can affect long-term health and quality of life. Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC) characterized by persistent unexplained symptoms, has a major impact on the health of many COVID-19 survivors. Although many individuals (up to 30%) experience some limited symptoms in the weeks and months following COVID-19, the prevalence of severe disabling Long COVID is less common (perhaps <5%). Long COVID syndromes are variable and include general (e.g., fatigue) and organ-system specific symptoms (e.g., shortness of breath, palpitations, neurocognitive symptoms), as well as symptoms resembling other medically unexplained syndromes (e.g., myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia, post-exertional malaise). For reasons not yet understood, female sex is a strong predictor of Long COVID, as is the presence of certain comorbidities, particularly obesity. Mechanisms that might plausibly contribute to Long COVID include irreversible tissue damage associated with acute infection, persistence of SARS-CoV-2 antigen or possibly a viral reservoir, residual or ongoing immune activation and inflammation, reactivation of other latent human viruses, microvascular dysregulation and thrombotic events, microbial translocation, dysbiosis, and autoimmune phenomena. These mechanisms may act in isolation or in combination to drive Long COVID syndromes. Notably, many if not all of these pathways have been implicated as possible mechanisms for the excess rate of cardiovascular disease and other comorbidities in people living with HIV. Industry engagement in Long COVID research is growing, and NIH funding for clinical trials is emerging through programs such as the RECOVER Initiative. As a result, we are entering an era of experimental medicine, in which potential interventions will be used as tools to probe the biology of the disease. This presentation will provide an overview of the proposed biological mechanisms contributing to Long COVID, with a focus on the current state of evidence, human and animal models, and the emerging therapeutic agenda.

Racial Differences in Blood Pressure and Autonomic Recovery Following Acute Supramaximal Exercise in Women.

Despite the growing popularity of high-intensity anaerobic exercise, little is known about the acute effects of this form of exercise on cardiovascular hemodynamics or autonomic modulation, which might provide insight into the individual assessment of responses to training load. The purpose of this study was to compare blood pressure and autonomic recovery following repeated bouts of acute supramaximal exercise in Black and White women. A convenience sample of twelve White and eight Black young, healthy women were recruited for this study and completed two consecutive bouts of supramaximal exercise on the cycle ergometer with 30 min of recovery in between. Brachial and central aortic blood pressures were assessed by tonometry (SphygmoCor Xcel) at rest and 15-min and 30-min following each exercise bout. Central aortic blood pressure was estimated using brachial pressure waveforms and customized software. Autonomic modulation was measured in a subset of ten participants by heart-rate variability and baroreflex sensitivity. Brachial mean arterial pressure and diastolic blood pressure were significantly higher in Blacks compared to Whites across time (race effect, p = 0.043 and p = 0.049, respectively). Very-low-frequency and low-frequency bands of heart rate variability, which are associated with sympathovagal balance and vasomotor tone, were 22.5% and 24.9% lower, respectively, in Blacks compared to Whites (race effect, p = 0.045 and p = 0.006, respectively). In conclusion, the preliminary findings of racial differences in blood pressure and autonomic recovery following supramaximal exercise warrant further investigations of tailored exercise prescriptions for Blacks and Whites.

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit.

BACKGROUND: Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown. METHODS: We retrospectively analyzed data collected during a single-center observational study (March 2020-November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany. All patients admitted to ICU due to acute COVID-19 disease during the study period were included (n = 361). Heart rate variability (HRV) and blood pressure variability (BPV) per day were used as clinical surrogates of dysautonomia and compared between survivors and non-survivors at different time points after admission. Intraindividual correlation of vital signs with laboratory parameters were calculated and corrected for age, sex and disease severity. RESULTS: Patients who deceased in ICU had a longer stay (median days ± IQR, survivors 11.0 ± 27.3, non-survivors 14.1 ± 18.7, P = 0.85), in contrast time spent under invasive ventilation was not significantly different (median hours ± IQR, survivors 322 ± 782, non-survivors 286 ± 434, P = 0.29). Reduced HRV and BPV predicted lethal outcome in patients staying on ICU longer than 10 days after adjustment for age, sex, and disease severity. Accordingly, HRV was significantly less correlated with inflammatory markers (e.g. CRP and Procalcitonin) and blood carbon dioxide in non-survivors in comparison to survivors indicating uncoupling between autonomic function and inflammation in non-survivors. CONCLUSIONS: Our study suggests autonomic dysfunction as a contributor to mortality in critically ill COVID-19 patients during the first waves of the pandemic. Serving as a surrogate for disease progression, these findings could contribute to the clinical management of COVID-19 patients admitted to the ICU. Furthermore, the suggested measure of dysautonomia and correlation with other laboratory parameters is non-invasive, simple, and cost-effective and should be evaluated as an additional outcome parameter in septic patients treated in the ICU in the future.

Pre-pandemic autonomic function as a predictor of the COVID clinical course in young adults.

Long coronavirus disease (COVID) is emerging as a common clinical entity in the current era. Autonomic dysfunction is one of the frequently reported post-COVID complications. We hypothesize a bi-directional relationship between the autonomic function and the COVID course. This postulation has been inadequately addressed in the literature. A retrospective cohort (pre and post-comparison) study was conducted on 30 young adults whose pre-COVID autonomic function test results were available. They were divided into case and control groups based on whether they tested reverse transcription polymerase chain reaction positive for COVID-19. Autonomic function tests were performed in both the case and control groups. COVID infection in healthy young adults shifts the sympatho-vagal balance from the pre-disease state. Postural orthostatic tachycardia syndrome was present in 35% of the COVID-affected group. COVID course parameters were found to be associated with parasympathetic reactivity and the baroreflex function. Baseline autonomic function (parasympathetic reactivity represented by Δ heart rate changes during deep breathing and 30:15 ratio during lying-to-standing test) was also associated with the COVID course, the post-COVID symptoms and the post-COVID autonomic function profile. Additionally, multiple regression analysis found that the baseline parasympathetic reactivity was a very important determinant of the clinical course of COVID, the post-COVID symptoms and the post-COVID autonomic profile. Sympatho-vagal balance shifts to parasympathetic withdrawal with sympathetic predominance due to COVID infection in healthy young adults. There is a bi-directional relationship between the autonomic function and the COVID course.