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.

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.

Postural Orthostatic Tachycardia Syndrome After COVID-19: A Systematic Review of Therapeutic Interventions.

ABSTRACT: Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.

Patient-Centered Paradigm for Managing Autonomic Long COVID Symptoms During Sports and Exercise.

ABSTRACT: This report highlights a new, patient-centered paradigm for managing post-COVID-19 dysautonomia symptoms during sports and exercise. The patient was a healthcare worker exposed before vaccination. She experienced postural orthostatic tachycardia plus exertional tachycardia, with postexertional fatigue, beginning a few weeks after testing positive for COVID-19. Stress test, echo, and an extensive dysautonomia evaluation were negative. Recommended nonpharmacological and pharmacological interventions were poorly tolerated. Prescription of a novel regimen of "basal-dose" ivabradine, plus very low-dose metoprolol according to an exertional "sliding scale" managed symptoms to an acceptable level for work and recreation.

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.

Autonomic function testing in long-COVID syndrome patients with orthostatic intolerance.

The association between dysautonomia and long-COVID syndrome has gained considerable interest. This study retrospectively characterized the findings of autonomic reflex screen (ARS) in long-COVID patients presenting with orthostatic intolerance (OI). Fourteen patients were identified. All patients had normal cardiovagal function and 2 patients had abnormal sudomotor function. The head-up tilt table (HUTT) was significantly abnormal in 3 patients showing postural orthostatic tachycardia syndrome (POTS). CASS ranged from 0 to 2. The most common clinical scenario was symptoms of orthostatic intolerance without demonstrable HUTT orthostatic tachycardia or orthostatic hypotension (OH) (n = 8, 57 %). In our case series, most long-COVID patients presenting to our laboratory with OI had no significant HUTT abnormalities; only 3 patients met the criteria for POTS.

Intermittent left bundle branch block with septal flash and postural orthostatic tachycardia syndrome in a young woman with long COVID-19.

The emerging entity, long COVID -19 is characterised by long-lasting dyspnoea, fatigue, cognitive dysfunction and other symptoms. Cardiac involvement manifested as conduction abnormalities, left ventricle mechanical dyssynchrony, dyspnoea, palpitation and postural orthostatic tachycardia syndrome (POTS) are common in long COVID-19. The direct viral damage to the myocardium or immune-mediated inflammation are postulated mechanisms. A woman in her forties presented with a 2-month history of chest pain, functional dyspnoea, palpitation and an episode of syncope after having been home-isolated for mild COVID infection. During clinical workup, a clustering of ECG and echocardiographic abnormalities including left bundle branch block, septal flash, and presystolic wave on spectral Doppler echocardiography, and POTS were detected. The echocardiographic findings together with POTS and persistent dyspnoea indicated the presence of a long COVID-19 state. The prevalence and clinical significance of these finding, as well as the impact on long-term prognosis, should be investigated in future studies.

Ongoing Dizziness Following Acute COVID-19 Infection: A Single Center Pediatric Case Series.

BACKGROUND: Dizziness is a common concern discussed at adolescent medical visits. In this series, we describe 9 pediatric patients with postacute sequelae of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) who presented with persistent, debilitating dizziness for weeks to months after their acute infection. METHODS: Among the 9 patients, median age was 14 years (range: 11 to 17), 6 were female, and 8 had not received any SARS-CoV-2 vaccines. Five patients met diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) by active standing testing and benefited from a combination of nonpharmacologic therapy (NPT) and medication. RESULTS: NPT alone did not improve symptoms in any patients. Patients who did not meet conventional criteria for POTS, but continued to have symptoms despite NPT compliance, also demonstrated subjective improvement in dizziness when medications were initiated. The majority of patients experienced improvement in dizziness and quality of life, including returning to sports teams and a regular school schedule. CONCLUSIONS: A review of the postacute sequelae of SARS-CoV-2 literature demonstrates increasing recognition of a subset of patients who develop autonomic dysfunction, including POTS, although the etiology and prognosis are not completely understood. Our case series aims to highlight the phenomenon of dysautonomia after acute SARS-CoV-2 infection and its response to therapy.

Prospective Evaluation of Autonomic Dysfunction in Post-Acute Sequela of COVID-19.

BACKGROUND: Patients with post-acute sequela of COVID-19 (PASC) often report symptoms of orthostatic intolerance and autonomic dysfunction. Numerous case reports link postural orthostatic tachycardia syndrome (POTS) to PASC. No prospective analysis has been performed. OBJECTIVES: This study performed head-up tilt table (HUTT) testing in symptomatic patients with PASC to evaluate for orthostatic intolerance suggestive of autonomic dysfunction. METHODS: We performed a prospective, observational evaluation of patients with PASC complaining of poor exertional tolerance, tachycardia with minimal activity or positional change, and palpitations. Exclusion criteria included pregnancy, pre-PASC autonomic dysfunction or syncope, or another potential explanation of PASC symptoms. All subjects underwent HUTT. RESULTS: Twenty-four patients with the described PASC symptoms were included. HUTT was performed a mean of 5.8 ± 3.5 months after symptom onset. Twenty-three of the 24 had orthostatic intolerance on HUTT, with 4 demonstrating POTS, 15 provoked orthostatic intolerance (POI) after nitroglycerin, 3 neurocardiogenic syncope, and 1 orthostatic hypotension. Compared with those with POTS, patients with POI described significantly earlier improvement of symptoms. CONCLUSIONS: This prospective evaluation of HUTT in patients with PASC revealed orthostatic intolerance on HUTT suggestive of autonomic dysfunction in nearly all subjects. Those with POI may be further along the path of clinical recovery than those demonstrating POTS.

Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome.

A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD). The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease. In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated. This case-control study validates our pilot study results that POTS patients have an activated innate immune system. Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as "non-POTS" subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules. Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001. Of particular interest were elevations of IL-1ß and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory. All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis.

Autonomic neuropathy as post-acute sequela of SARS-CoV-2 infection: a case report.

Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae of SARS-CoV-2 infections. Different pathophysiologic mechanisms can be involved in the development of orthostatic intolerance including hypovolemia due to gastrointestinal dysfunction, fatigue-associated deconditioning, and hyperadrenergic state due to pandemic-related anxiety. Additionally, there has been a well-established association of a common primary autonomic disorder like postural orthostatic tachycardia syndrome, a subtype of orthostatic intolerance, with antecedent viral infections. Here we report a case of neuropathic type postural orthostatic tachycardia syndrome as a form of autonomic neuropathy that developed following COVID-19 infection.

Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies.

The effects of coronavirus disease 2019 (COVID-19), a highly transmissible infectious respiratory disease that has initiated an ongoing pandemic since early 2020, do not always end in the acute phase. Depending on the study referred, about 10%-30% (or more) of COVID-19 survivors may develop long-COVID or post-COVID-19 syndrome (PCS), characterised by persistent symptoms (most commonly fatigue, dyspnoea, and cognitive impairments) lasting for 3 months or more after acute COVID-19. While the pathophysiological mechanisms of PCS have been extensively described elsewhere, the subtypes of PCS have not. Owing to its highly multifaceted nature, this review proposes and characterises six subtypes of PCS based on the existing literature. The subtypes are non-severe COVID-19 multi-organ sequelae (NSC-MOS), pulmonary fibrosis sequelae (PFS), myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), post-intensive care syndrome (PICS) and medical or clinical sequelae (MCS). Original studies supporting each of these subtypes are documented in this review, as well as their respective symptoms and potential interventions. Ultimately, the subtyping proposed herein aims to provide better clarity on the current understanding of PCS.

COVID-19-induced postural orthostatic tachycardia syndrome treated with ivabradine.

A 22-year-old woman was referred with exertional dyspnoea and chest tightness 3 weeks following a diagnosis of COVID-19. Evaluation revealed a resting sinus tachycardia and criteria for postural orthostatic tachycardia syndrome were met. After non-pharmacological interventions failed to yield symptomatic improvement, ivabradine was commenced. This intervention was followed by a substantial improvement in the patient's exercise tolerance and energy levels and an objective reduction in supine and standing heart rate.