Postural orthostatic tachycardia syndrome-like symptoms following COVID-19 vaccination: An overview of clinical literature.

BACKGROUND: Postural Orthostatic Tachycardia Syndrome (POTS) is a common condition affecting more than 170 people per 100,000 population. However, POTS following COVID-19 vaccination remains a rare reporting in the medical literature. OBJECTIVE: We, herein, summarize and highlight the evidence that has been reported regarding POTS-like symptoms following COVID-19 vaccination. METHODS: We conducted a literature search and summarized the findings in the form of a narrative commentary. All types of publications (case reports/series, original articles, letters to editors, brief communications etc.) in English language were included. RESULTS: Whilst the exact pathogenetic mechanism behind POTS is yet to elucidated, there has been increasing evidence pointing towards an autoimmune dysfunction. Females were found to be predominantly affected (72%) with age range from 17 years to 52 years. Additionally, it seems that POTS-like symptoms could be triggered after immunization with Pfizer- BioNTech, Moderna, and Oxford-AstraZeneca COVID-19 vaccines. The symptoms typically appear within the first week, depending upon previous exposure to the virus and presence of other systemic conditions. In some patients, the condition is self-resolving. However, in others, non-pharmacological interventions coupled with negative ionotropic medications can be used for symptomatic management of the patients. CONCLUSIONS: Timely diagnosis and proper treatment are quintessential for ensuring early alleviation (and in some cases complete resolution) of symptoms. Furthermore, there may be episodes of relapse. Overall prognosis of the new-onset POTS-like symptoms is difficult to predict based on current literature.

Detecting Orthostatic Intolerance in Long COVID in a Clinic Setting.

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.

Autoimmunity in Long Covid and POTS.

Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.

Corona With Lyme: A Long COVID Case Study.

The longevity of the coronavirus disease 2019 (COVID-19) pandemic has necessitated continued discussion about the long-term impacts of SARS-CoV-2 infection. Many who develop an acute COVID-19 infection will later face a constellation of enduring symptoms of varying severity, otherwise known as long COVID. As the pandemic reaches its inevitable endemicity, the long COVID patient population will undoubtedly grow and require improved recognition and management. The case presented describes the three-year arc of a previously healthy 26-year-old female medical student from initial infection and induction of long COVID symptomology to near-total remission of the disease. In doing so, the course of this unique post-viral illness and the trials and errors of myriad treatment options will be chronologized, thereby contributing to the continued demand for understanding this mystifying disease.

Postural Orthostatic Tachycardia Syndrome in COVID-19: A Contemporary Review of Mechanisms, Clinical Course and Management.

The long-term implications of COVID-19 have garnered increasing interest in recent months, with Long-COVID impacting over 65 million individuals worldwide. Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. POTS remains very challenging to diagnose and manage - this review aims to provide a brief overview of POTS as a whole and goes on to summarize the available literature pertaining to POTS in the setting of COVID-19. We provide a review of available clinical reports, outline proposed pathophysiological mechanisms and end with a brief note on management considerations.

Impact of the COVID-19 pandemic on clinical autonomic practice in Europe A survey of the European Academy of Neurology (EAN) and the European Federation of Autonomic Societies (EFAS).

OBJECTIVE: To investigate the impact of the coronavirus-disease-2019 (COVID-19) pandemic on European clinical autonomic practice. METHODS: Eighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021. RESULTS: Forty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every-third center reported major adverse events due to postponed examinations or visits. The most frequent newly-diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension, and recurrent vasovagal syncope, deemed likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new-onset of orthostatic intolerance, but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly-diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently POTS and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50-100% recovery rates at follow-up. CONCLUSIONS: Cardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, while the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints.

Management of Post-Viral Postural Orthostatic Tachycardia Syndrome With Craniosacral Therapy.

Postural Orthostatic Tachycardia Syndrome (POTS) is a rare disorder of the autonomic nervous system. The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed. This case report is about a patient with post-viral neuropathic POTS. Neuropathic POTS is believed to be due to the damage of small nerve fibers that regulate the constriction of the blood vessels in the limb and abdomen, which leads to interference with vasoconstriction, and therefore causes tachycardia. Current literature emphasizes a treatment that is based on lifestyle modifications, such as increasing water and salt intake, and symptomatic pharmacological treatment. In this case, the 39-year-old male ptient was treated with osteopathic manipulative treatment (OMT), specifically the compression of the fourth ventricle (CV4), which has been associated with the production of hyperparasympathetic and anti-inflammatory effects and, hence, helps overcome the small-fiber neuropathy caused by the viral illness. We found that the CV4 technique led to the successful remission of the patient's symptoms. Therefore, we propose craniosacral therapy as a successful single management modality in patients with POTS.

COVID-19 Induced Postural Orthostatic Tachycardia Syndrome (POTS): A Review.

POTS (Postural Orthostatic Tachycardia Syndrome) is a multisystem disorder characterized by the abnormal autonomic response to an upright posture, causing orthostatic intolerance and excessive tachycardia without hypotension. Recent reports suggest that a significant percentage of COVID-19 survivors develop POTS within 6 to 8 months of infection. Prominent symptoms of POTS include fatigue, orthostatic intolerance, tachycardia, and cognitive impairment. The exact mechanisms of post-COVID-19 POTS are unclear. Still, different hypotheses have been given, including autoantibody production against autonomic nerve fibers, direct toxic effects of SARS-CoV-2, or sympathetic nervous system stimulation secondary to infection. Physicians should have a high suspicion of POTS in COVID-19 survival when presented with symptoms of autonomic dysfunction and should conduct diagnostic tests like the Tilt table and others to confirm it. The management of COVID-19-related POTS requires a comprehensive approach. Most patients respond to initial non-pharmacological options, but when the symptoms become more severe and they do not respond to the non-pharmacological approach, pharmacological options are considered. We have limited understanding and knowledge of post-COVID-19 POTS, and further research is warranted to improve our understanding and formulate a better management plan.

Suspected COVID-19 mRNA Vaccine-Induced Postural Orthostatic Tachycardia Syndrome.

We present a case of a 15-year-old South Asian male who developed suspected postural orthostatic tachycardia syndrome (POTS) two weeks after receiving the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine booster, which was successfully managed with low-dose fludrocortisone and ivabradine. Clinicians should be aware of the Pfizer-BioNTech COVID-19 vaccine being implicated with the onset of POTS.

Autonomic Nerve Involvement in Post-Acute Sequelae of SARS-CoV-2 Syndrome (PASC).

The novel SARS-CoV-2 virus and resulting COVID-19 global pandemic emerged in 2019 and continues into 2022. While mortality from COVID-19 is slowly declining, a subset of patients have developed chronic, debilitating symptoms following complete recovery from acute infection with COVID-19. Termed as post-acute sequelae of SARS-CoV-2 syndrome (PASC), the underlying pathophysiology of PASC is still not well understood. Given the similarity between the clinical phenotypes of PASC and postural orthostatic tachycardia syndrome (POTS), it has been postulated that dysautonomia may play a role in the pathophysiology of PASC. However, there have been only a few studies that have examined autonomic function in PASC. In this retrospective study, we performed an analysis of autonomic nerve function testing in PASC patients and compared the results with those of POTS patients and healthy controls. Our results suggest that a significant number of PASC patients have abnormal autonomic function tests, and their clinical features are indistinguishable from POTS.

Autoimmune autonomic nervous system imbalance and conditions: Chronic fatigue syndrome, fibromyalgia, silicone breast implants, COVID and post-COVID syndrome, sick building syndrome, post-orthostatic tachycardia syndrome, autoimmune diseases and autoimmune/inflammatory syndrome induced by adjuvants.

Chronic fatigue syndrome (CFS), fibromyalgia, silicone breast implants syndrome (SBIs), COVID and post-COVID syndrome (PCS), sick building syndrome (SBS), post-orthostatic tachycardia syndrome (POTS), autoimmune diseases and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are frequently accompanied by clinical symptoms characteristic for dysautonomia: severe fatigue, dizziness, fogginess, memory loss, dry mouth and eyes, hearing dysfunction, tachycardia etc. The recent discovery of an imbalance of autoantibodies against G protein-coupled receptors (GPCR) in some autoimmune diseases, post-COVID syndrome, SBIs allowed researchers to assume the novel mechanism in these conditions - autoimmune autonomic nervous system imbalance. In this review, all data published on an imbalance of autoantibodies against GPCR, clinical symptoms and pathogenic mechanisms in CFS, Fibromyalgia, SBIs, COVID and PCS, SBS, POTS, and some autoimmune diseases were analyzed. Possible criteria to diagnose the autoimmune autonomic nervous system imbalance were created.

Postural orthostatic tachycardia syndrome and orthostatic hypotension post COVID-19.

BACKGROUND: Novel coronavirus causes coronavirus disease -19 (COVID-19). The hallmark is acute respiratory distress syndrome, but other system's involvement is less illustrated. Our goal was to evaluate the manifestation of COVID-19 on one of the overlaps of the cardiovascular and nervous system, namely: Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Hypotension (OH). METHODS: This single-center cross-sectional observational study encompassed 60 consecutive patients that were hospitalized and recovered from severe or critical COVID-19. At the time of discharge, Blood Pressure (BP), Heart Rate (HR) in the supine and upright position (1st, 3rd, 5th and 10th minutes) were measured. Symptomatic patients were reevaluated 2 months later. RESULTS: The mean age of patients was 56.6 (±16.2) years and 42 patients were male (70%). The most frequent cardiovascular risk factor was hypertension (35%). OH and POTS were detected in 29(48.3%) and 10(16.7%) of the patients respectively at the time of hospital discharge. The mean age of patients with OH was higher than POTS and POTS was frequent in the elderly. Two months later among 10 patients with POTS, the sign and symptoms were resolved in 8(80%). Two (20%) patients who still had positive signs and symptoms of POTS were older than 65 years. Among 29 patients with OH, the signs and symptoms were resolved in 26(89.7%). CONCLUSION: In our study 65% of patients had OH or POTs on the day of hospital discharge, Complete recovery is gradual and needs several additional weeks. This is one of the aspects of the entity recently named "Long COVID".

POTS and Pregnancy: A Review of Literature and Recommendations for Evaluation and Treatment.

Postural Orthostatic Tachycardia Syndrome (POTS) is a disorder of the autonomic nervous system most commonly affecting women of reproductive age. Studies on POTS and pregnancy are limited, and there is a lack of clinical guidelines regarding assessment and management of pregnant women with POTS. The purpose of this review is to summarize data from the available studies on the topic of pregnancy in POTS and common comorbid conditions and to provide the clinical recommendations regarding evaluation and treatment of POTS in pregnant women, based on the available studies and clinical experience. We conclude that pregnancy appears to be safe for women with POTS and is best managed by a multi-disciplinary team with knowledge of POTS and its various comorbidities. Importantly, large, prospective studies are needed to better delineate the course and outcomes of pregnancy, as well as possible pregnancy-related complications in women with POTS. Clinicians should be aware of the clinical presentation, diagnostic criteria, and treatment options in pregnant women with POTS to optimize outcomes and improve medical care during pregnancy and post-partum period.

[Myalgic encephalomyelitis/chronic fatigue syndrome: an overview of current evidence]. / Myalgische Enzephalomyelitis/chronisches Fatigue-Syndrom: eine Übersicht zur aktuellen Evidenz.

Over the past 5 years both media and scientific interest has surged regarding the disorder myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS), not least because of the clinically similar manifestation in long COVID or post-COVID. In this review we discuss the process of clinical diagnosis and randomized controlled therapeutic studies on ME/CFS, and the similarities or differences to long COVID and post-COVID. So far, neither clear pathophysiologically causal nor therapeutic evidence-based results on ME/CFS have been identified in the many years of scientific research. Given the evident psychiatric comorbidity rates in patients with a diagnosis of ME/CFS, a psychosomatic etiology of this syndrome should be considered. Furthermore, a precise and reliable diagnostic classification based on stricter criteria would benefit both pathophysiological and therapeutic research.

Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) has been described early after the onset of the COVID-19 infection, but also orthostatic hypotension (OH). In the present study, we hypothesized that orthostatic intolerance decreases over time. METHODS: In 29 long-haul COVID-19 (LHC) patients, a tilt test was performed, including measurements of cerebral blood flow (CBF) by extracranial Doppler. The time interval between the onset of infection and the tilt test varied between 3 and 28 months. RESULTS: In the first 12 months after the infection, 71% of the LHC patients showed POTS and after 24 months none of them. In the first 12 months, 29% of patients had a normal heart rate and blood pressure response (normHRBP) and after 24 months 75% (distribution of POTS, OH, and a normHRBP over time: p < 0.0001). Linear regression showed that, over time, there was a decrease in the abnormal CBF during the tilt (p = 0.024) but remained abnormal. CONCLUSION: In LHC patients, hemodynamic abnormalities of a tilt test change over time. Patients studied early after the onset of the disease mainly exhibit POTS, but patients studied later in the time course mainly show a normHRBP or OH. In addition, the abnormal CBF reduction improves over time, but CBF remains abnormal.

An Exercise Prescription as a Novel Management Strategy for Treatment of Long COVID.

Mechanisms causing the post-acute sequelae of SARS-CoV-2 (long COVID) remain elusive, but the clinical phenotype is consistent with cardiac deconditioning. We report a case series of patients with long COVID whose symptoms improved/resolved with exercise and present exercise training as a novel therapeutic strategy for management of long COVID syndrome. (Level of Difficulty: Intermediate.).

Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome.

BACKGROUND: The autonomic nervous system (ANS) is a complex network where sympathetic and parasympathetic domains interact inside and outside of the network. Correlation-based network analysis (NA) is a novel approach enabling the quantification of these interactions. The aim of this study is to assess the applicability of NA to assess relationships between autonomic, sensory, respiratory, cerebrovascular, and inflammatory markers on post-acute sequela of COVID-19 (PASC) and postural tachycardia syndrome (POTS). METHODS: In this retrospective study, datasets from PASC (n = 15), POTS (n = 15), and matched controls (n = 11) were analyzed. Networks were constructed from surveys (autonomic and sensory), autonomic tests (deep breathing, Valsalva maneuver, tilt, and sudomotor test) results using heart rate, blood pressure, cerebral blood flow velocity (CBFv), capnography, skin biopsies for assessment of small fiber neuropathy (SFN), and various inflammatory markers. Networks were characterized by clusters and centrality metrics. RESULTS: Standard analysis showed widespread abnormalities including reduced orthostatic CBFv in 100%/88% (PASC/POTS), SFN 77%/88%, mild-to-moderate dysautonomia 100%/100%, hypocapnia 87%/100%, and elevated inflammatory markers. NA showed different signatures for both disorders with centrality metrics of vascular and inflammatory variables playing prominent roles in differentiating PASC from POTS. CONCLUSIONS: NA is suitable for a relationship analysis between autonomic and nonautonomic components. Our preliminary analyses indicate that NA can expand the value of autonomic testing and provide new insight into the functioning of the ANS and related systems in complex disease processes such as PASC and POTS.

Postural orthostatic tachycardia syndrome: pathophysiology, management, and experimental therapies.

INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies. AREAS COVERED: In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic. EXPERT OPINION: Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

Orthostatic and Exercise Intolerance in Recreational and Competitive Athletes With Long COVID.

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (PASC) infection is particularly concerning to athletes who place a high premium on cardiovascular performance and competition. This initial case series shows the overlap between PASC and orthostatic intolerance in athletes, reveals the diagnostic challenges, and highlights the role of graded exercise training in this population. (Level of Difficulty: Advanced.).

Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment ("brain fog"), orthostatic intolerance (OI) and other symptoms ("Long COVID"). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing. Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app. Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT. Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01). Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.