Postural Orthostatic Tachycardia Syndrome (POTS) and Neurally-Mediated Hypotension (NMH) are heterogeneous syndromes characterized by dysautonomia and multisystem symptoms. Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined. Patients from the Johns Hopkins POTS Clinic completed surveys assessing hives frequency and symptom burden using the Malmö POTS, the Composite Autonomic Symptom Score (COMPASS)-31, and a pain questionnaire. Associations between hives and clinical features were evaluated among patients with confirmed POTS, NMH, or clinically diagnosed orthostatic intolerance. Among 188 respondents, 80 (42.6%) reported hives sometimes and 33 (17.6%) reported hives often or always. Increasing hives frequency was associated with higher Malmö POTS scores and greater autonomic symptom burden across multiple COMPASS-31 subdomains, including gastrointestinal, bladder, and vasomotor symptoms (all  < 0.05). Hives was also associated with pain (OR 3.47, 95% CI 1.54-7.77,  = 0.002) and tingling (OR 5.73, CI 2.15-15.26,  < 0.001), but not orthostatic symptoms. These associations persisted after multivariable adjustment. Hives are common in orthostatic intolerance syndromes and are associated with increased symptom burden. Future studies are needed to clarify the role of mast cell activation and evaluate mast cell-targeted therapies.

Postural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder of heterogeneous pathophysiology involving relative sympathetic overactivity and/or parasympathetic hypofunction. Postural orthostatic tachycardia syndrome is characterized by exaggerated postural tachycardia in the absence of orthostatic hypotension, in conjunction with orthostatic intolerance and other cardiovascular and neurologic features. We report a 30-year-old woman with POTS who experienced significant improvement with pyridostigmine. The whole genome sequencing demonstrated four single nucleotide polymorphisms-AchE, BChE, PEMT, and CHDH-variants involved in acetylcholine processing that may have led to acetylcholine deficiency and resultant parasympathetic hypofunction with relative sympathetic hyperactivity in this patient. Her Composite Autonomic Symptom Score-31 (COMPASS-31) after initiation of pyridostigmine decreased from 56.15 pre-treatment to 32 post-treatment, which indicated a 43% improvement in autonomic symptom burden, while her daily step count increased from an average of 4000 steps pre- to 7500 steps post-treatment with pyridostigmine. We hypothesize that genetic variants in acetylcholine processing may result in acetylcholine deficiency state and may represent one of many pathophysiologic mechanisms of POTS. Whole genome sequencing and validated genetic tests for these and other genetic variants may be valuable diagnostic tools in delineating specific pathophysiology, POTS phenotypes, and personalized treatment approaches.

Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common type of inherited connective tissue disorder, often presenting with chronic widespread myofascial pain, autonomic dysfunction, soft-tissue fragility, and psychiatric comorbidities. Pain is often multifactorial and refractory to conventional therapies. We describe a young adult with longstanding hypermobility, recurrent subluxations, chronic periscapular pain, migrainous headaches, and dysautonomia who achieved marked clinical improvement with lidocaine-based therapies, including trigger-point injections (TPIs) and scheduled intravenous lidocaine infusion. TPIs provided more than 50% relief of the myofascial pain for over one month, which is significantly longer than the typical duration of conservative treatments. A lidocaine infusion was subsequently administered to provide extended and more widespread pain relief, resulting in a favorable clinical outcome. This case illustrates the value of lidocaine as part of a multimodal strategy in managing complex hypermobility-related pain syndromes.

The association between blood pressure variability (BPV) or heart rate variability (HRV) and the baroreflex is well established. However, the role of the vestibular-autonomic reflex in regulating BP and HR stability has primarily been explored only in experimental studies. We aimed to delineate the association of BPV and HRV with otolith function in postural orthostatic tachycardia syndrome (POTS). We retrospectively analyzed data from consecutive patients with POTS recruited between April 2021 and April 2025 at a tertiary referral-based hospital in South Korea. All patients underwent a head-up tilt table test using a Finometer device and cervical (cVEMP) and ocular vestibular evoked-myogenic potentials (oVEMP). The Finometer data were analyzed using a power spectral analysis. The Finometer, cVEMP, and oVEMP data were compared with those of 32 age- and sex-matched healthy participants. A total of 47 patients with POTS (mean age standard deviation [SD] = 33 10 years; 30 female patients) and 32 age- and sex-matched healthy participants were included for analysis. The n1-p1 amplitude of oVEMP was larger in patients with POTS than in healthy participants (p = 0.002). p13 latency was negatively correlated with the SD of heart rate in the supine position in patients with POTS (p = 0.001), a trend not observed in healthy participants. The n1-p1 amplitude (odds ratio [95% confidence interval] = 1.27 [1.08-1.49], p = 0.004) and root mean square of successive differences (RMSSD) during tilting (0.82 [0.72-0.93], p = 0.001) were associated with POTS after adjusting for other covariates. Otolithic function may play a role in accentuating BPV and HRV in POTS by contributing to enhanced sympathetic outflow.

Despite the central role of exercise in treating postural orthostatic tachycardia syndrome (POTS) there have been no studies on the subjective experience of exercise interventions and/or recommendations among this patient population. The purpose of this mixed-methods study was to provide greater understanding of the perceived barriers, preferences, perceptions of exercise, and experiences implementing exercise recommendations for adults with POTS in order to optimize treatment recommendations and intervention design. This study consisted of a series of focus groups (n = 29) and an online survey of adults with POTS (n = 255) focusing on exercise engagement, beliefs, barriers, and facilitators. Qualitative data were analyzed using an iterative inductive-deductive approach, informed by social cognitive theory, which resulted in a conceptual framework and a series of themes. Survey results showed that participants reported a wide range of exercise frequency prior to the onset of POTS symptoms, and overall lower exercise engagement post-POTS. In both survey results and qualitative findings, participants reported believing that exercise is important in managing POTS, but identified barriers to exercise training, including most saliently, their symptom burden. Participants also identified important needs and facilitating factors that could support them in engaging in regular exercise to help manage their condition. These findings shed light on the patient experience of exercise in POTS, which can inform both the tailoring of exercise recommendations and the design of interventions to support exercise engagement specific to the POTS population.

Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright position in the absence of orthostatic hypotension, defined as a sustained decrease in systolic blood pressure (SBP) of ≥ 20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 min of standing. In children, a sustained HR increment of at least 40 bpm is required for diagnosis of POTS. POTS is a common condition in adults and children suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In daily clinical practice, therapeutic recommendations are rare and evidence is missing. The objective of this review is to present the current knowledge on non-pharmacological and pharmacological approaches in POTS with a special focus on POTS therapy in children and people with ME/CFS. Of 3853 studies, 45 studies were included in the systematic review. Evidence on therapy in POTS is rare and large randomized controlled trials (RCT) on single interventions are needed. Non-pharmacological approaches such as the use of compression garments, physical training, salt supplementation and transdermal vagal nerve stimulation could be possible treatment options in POTS because they are easy to implement as first-line therapeutic measures in clinical practice. For pharmaceuticals, several studies showed significant effects following therapy with ivabradine and β-adrenergic blocking agents. There are single studies which imply that midodrine (hydrochloride) and pyridostigmine seem to have a beneficial effect on hemodynamics in POTS.

Twenty five percent of children who sustain a mild traumatic brain injury (mTBI) or concussion experience persisting post-concussion symptoms (PPCS). The symptoms of PPCS significantly overlap with postural orthostatic tachycardia syndrome (POTS). We aimed to review the literature and investigate the prevalence of POTS in children and adolescents recovering from mTBI. This single centre controlled cross-sectional cohort study recruited children (aged 8-18 years inclusive) diagnosed with mTBI in the emergency department. At 4-6 weeks postinjury, children completed the Active Stand Test. The primary outcome was change in heart rate alongside clinical symptoms consistent with POTS. A total of 113 participants (64 PPCS, 24 mTBI with no clinical symptoms [asymptomatic], and 25 healthy controls) of similar age (mean 13.9 years) and sex (n = 55 [48.7%] male) underwent orthostatic testing. There were no significant group differences in heart rate or blood pressure at baseline, or within 10 minutes of standing. Three (4.8%) symptomatic participants satisfied POTS diagnostic criteria, compared to zero asymptomatic and one (4.2%) control participant. Using the Active Stand Test, a small proportion of children with PPCS satisfied clinical POTS criteria. Although it should be considered in the differential diagnosis, POTS is not common nor overrepresented in PPCS.

BackgroundIndividuals with neurologic impairment, such as brain injury, are more likely to have autonomic dysfunction, including POTS, but often experience a lack of treatment options and access to quality care.ObjectiveExamine the feasibility and outcomes of a group-based multimodal rehabilitation training program.MethodsNineteen females, ages 18-53 (M = 28.6) completed the outpatient training program. The intervention included eight 50-min weekly sessions using an interdisciplinary, multimodal approach, including education, movement, and mindful self-compassion. Participants completed demographic and medical history and assessment for baseline orthostatic intolerance. At pre-training, post-training, and follow-up, participants completed the Modified Fatigue Impact Scale (MFIS), Lower Extremity Functional Scale (LEFS), Rand 36-Item Health Survey 1.0 (RAND-36), Trail Making Test (A and B) (TMT-A, TMT-B), 10-Meter Walk Test (10MWT), and grip strength testing.ResultsAt baseline, participants were significantly below norms in daily function (p < 0.001), grip strength (p ≤ 0.001) gait speed (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Between pre-training and follow-up, participants showed significant improvement across function in daily life tasks (p < 0.01); grip strength in the dominant (p < 0.01) and non-dominant (p < 0.01) hands; gait speed (p < 0.05); levels of fatigue (p < 0.05); cognitive performance (p < 0.05); and quality of life (p < 0.05).ConclusionIndividuals with POTS face functional challenges that can be significantly and objectively improved through multimodal rehabilitation. There is a need for provider education and further research to optimize care and quality of life for individuals with POTS.

Postural Orthostatic Tachycardia Syndrome (POTS) is a debilitating condition of the autonomic nervous system with no clear referral, diagnosis, and treatment pathways. Patients experience high levels of symptoms and moderate levels of distress. The purpose of this study was to explore biopsychosocial factors associated with distress in those under investigation for POTS, to identify potential targets for intervention. A longitudinal, quantitative survey. Participants (n = 149) completed demographic, psychosocial, and symptom questionnaires prior to a diagnostic POTS clinic visit and 6 months follow-up (n = 98). Correlation and regression analyses were used to identify factors associated with distress at baseline (within one month before diagnostic hospital visit) and at 6 months follow up. At baseline, distress levels were moderate and greater symptom focusing, all-or-nothing and avoidance behaviours, threatening views of the illness, emotional reactivity, cardiac anxiety, POTS symptoms, number of specialists seen, lower social support, and younger age were significantly associated with higher levels of baseline distress. The baseline regression model including all demographic, clinical, and psychosocial factors explained 61.2 % of the variance in distress, with the psychosocial variables collectively explaining 55.6 % of this variance (F = 11.06, p < .001). There was no significant difference between distress levels at baseline and follow-up. Psychosocial variables explained 4.7 % of the variance (F = 0.76, p = .665) in changes in distress scores over 6 months. Baseline distress scores accounted for the vast majority of variance in distress at follow-up. This study identified key novel psychosocial factors that were significantly associated with distress which could be potential targets for intervention. Additional factors such as younger age and a higher number of specialists seen were also associated with higher levels of distress, which merits attention when assessing patients' psychological wellbeing this patient group. Distress levels did not significantly change following the specialist consultation and investigation.

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with challenging diagnosis and management. This cross-sectional, multi-national, web-based physician chart audit described clinical features and management of POTS, offering insights into disease burden and outcomes before and after the COVID-19 pandemic. Physicians (n = 153), primarily cardiologists (77.1 %), reported data from 599 patients from two cohorts: 1) POTS not triggered by COVID-19 (n = 361) and 2) POTS triggered by COVID-19 (n = 238). Overall, most patients experienced POTS symptoms onset between the ages of 18 and 39 years (33 %), with 13 % presenting symptom onset before 18 years of age. Over 70 % had at least one pre-existing medical condition. Most patients underwent 5-8 tests to define POTS diagnosis. Around 80 % received incorrect diagnoses before POTS confirmation, and 25 % waited over a year for diagnosis. Although some patients showed reduction in symptom severity over time, symptoms were still persistent at last consultation. Non-pharmacological interventions were common in the first treatment line. In subsequent lines, there was an increase in pharmacological treatments, with beta-blockers and ivabradine being the most frequently prescribed medications. Comparative analysis between pre- and post-COVID-19 POTS showed that while POTS patients triggered by COVID-19 were somewhat older and had fewer comorbidities, differences were not clinically meaningful, suggesting similar diagnostic, management and treatment patterns. Regional differences in diagnoses and treatment patterns were observed between US and Europe. This study highlights the challenges faced by POTS patients, while providing insights into the diagnostic and treatment approaches in real-world settings.

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder mainly of orthostatic intolerance, often accompanied by a spectrum of symptoms related to autonomic nervous system dysfunction. Although the diagnostic criteria require an orthostatic challenge test, the associated symptom burden can be broad and is often missed by treating healthcare professionals, resulting in significant diagnostic delay. Treatment of this highly heterogenous condition is nuanced and consists of non-pharmacologic and pharmacologic approaches. Availability of POTS care is limited, with a dearth of medical specialists or general practitioners specialising in autonomic medicine. The complexity of care for those with POTS necessitates a multidisciplinary approach due to the need for extended appointment times and frequent follow-ups to monitor therapeutic response and progress. This should include a primary team consisting of a general practitioner and trained autonomic physicians with specialist nurses, allied health professionals, and any other specialists required to manage the affected systems. This state-of-the-art review aims to cover the key aspects of diagnosing and managing POTS, including special neurological, gastroenterological, psychological, and paediatric considerations. There is an urgent need to provide services that meet the needs of the growing POTS population.

A previous study showed a high prevalence of central sensitization syndrome (CSS) in patients with autonomic symptoms. The prevalence of CSS in postural tachycardia syndrome (POTS), a form of dysautonomia, is unknown. To analyze the prevalence of CSS in POTS. This case-control study included patients with a POTS diagnosis confirmed by autonomic testing at Brigham and Women's Faulkner Hospital between 2022 and 2025. Data were analyzed from April to August 2025. POTS with and without CSS. Central Sensitization Inventory (to assess central sensitization syndrome [CSS]), COMPASS-31 (autonomic symptoms), Neuropathy Total Symptom Score-6 (NTSS-6, sensory symptoms), PROMIS (global health), and autonomic testing (Valsalva maneuver, deep breathing, sudomotor function, and head-up tilt) with skin biopsies. Primary outcome was the central sensitization inventory score with secondary outcomes individual test performances. This study included 305 patients with POTS, of whom 264 (86.6%) met criteria for CSS (mean [SD] age, 33.21 [10.75] years; 30 males [11.4%]; 234 females [88.6%]). Patients with CSS compared with those without CSS had longer duration of symptoms, were more frequently female, exhibited higher rates of anxiety (195 [73.9%] vs 20 [48.8%]; P = .002), depression (168 [63.6% vs 14 [34.1%]; P = .001), fibromyalgia (46 [17.4%] vs 0 [0%]; P = .008), irritable bowel syndrome (IBS, 90 [34.1%] vs 7 [17.1%]; P = .046), headaches (176 [66.7%] vs 12 [29.3 %]; P < .001), treatment with antihistamine medication (136 [51.5%] vs 13 [31.7%]; P = .03), psychiatric medication (163 [61.7%] vs 17 [41.5 %]; P = .02), pain medication (127 [48.1%] vs 8 [19.5%]; P = .001), and gastrointestinal medication (82 [31.1%] vs 5 [12.2 %]; P = .02), and had higher COMPASS-31 scores (51.93 [13.23] vs 31.18 [10.49]; P < .001), NTSS-6 scores (11.32 [4.86] vs 4.44 [3.32]; P < .001), NRS scores (3.26 [2.73] vs 0.54 [1.21]; P < .001), and worse PROMIS scores (20.36 [5.45] vs 27.96 [4.73]; P < .001). Autonomic tests showed lower orthostatic end-tidal carbon dioxide (27.59 [6.39] mm HG vs 29.46 [4.68] mm HG; P = .002) and a greater orthostatic decline in cerebral blood flow velocity (17.08 [8.72] cm/sec vs 13.68 [5.04] cm/sec; P < .001) in the CSS group. Both groups had similar prevalence of autonomic failure (223 [84.5%] vs. 33 [80.5%]; P = .67, mostly mild intensity), and abnormal skin biopsy (43% in both groups). These findings suggest that CSS was common in patients with POTS and may represent a higher-order sequela of cerebrovascular, respiratory, and autonomic dysregulation. This heightened central processing may amplify symptom perception through altered interoceptive signaling. Central sensitization and autonomic impairment may coexist, and management should focus on both conditions.

This report presents an unusual case of sequential, pharmacologically confirmed iatrogenic bilateral Horner syndrome followed by bilateral Adie's tonic pupil, highlighting the spectrum of ocular dysautonomia associated with long coronavirus disease 2019 (COVID-19). A 41-year-old woman with a history of coronavirus disease 2019 reinfection and multiple comorbidities developed pharmacologically confirmed bilateral Horner syndrome after bilateral stellate ganglion blocks. Subsequent worsening of long COVID-19 symptoms alongside systemic dysautonomia emerged, including postural orthostatic tachycardia syndrome, orthostatic hypotension, and mast cell activation syndrome. The patient then presented with bilateral, poorly reactive, enlarged pupils, and light-near dissociation. Bilateral Adie's tonic pupil was pharmacologically confirmed. Neuroimaging and laboratory workup were unremarkable. As more cases of long COVID-19 emerge, physicians should be aware that long COVID-19 can manifest with rare neuro-ophthalmic presentations, including bilateral pupillary autonomic dysfunction.

Orthostatic intolerance (OI) is characterized by the inability to maintain an upright posture without experiencing severe signs and symptoms, including hypotension, palpitations, light-headedness, pallor, fatigue, weakness, dizziness, impaired concentration, tremulousness, and nausea. The majority of patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) exhibit OI, which is the primary factor restricting daily functional capacity. During an upright posture, approximately 800 mL of blood is translocated from the intrathoracic venous compartment to the veins of the buttocks, pelvis, and legs. Under normal conditions, compensatory cardiovascular responses to this orthostatic stress include activation of the muscle pump through calf muscle contraction and a neurogenically mediated increase in heart rate and in systemic vascular resistance. The majority of the symptoms of OI are believed to be cardiovascular and related to reduced cerebral blood flow and excessive activation of the sympathetic nervous system. However, compensatory sympathetic activation is essential for maintaining orthostasis. Many patients have a small left ventricle and associated low cardiac output. In addition, both the renin-aldosterone and antidiuretic hormone systems that regulate circulatory blood volume were downregulated. Postural stability is necessary for maintaining the static balance critical for performing many daily activities. Recently studies have reported that postural instability or disequilibrium, potentially associated with central vestibular dysfunction, should be considered to be involved in the pathogenesis of OI among patients with ME/CFS. Disequilibrium should be recognized as an important cause of OI in those patients.

Long COVID has been an important health concern in children and adolescents, yet factors associated with its development remain incompletely understood. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely prescribed for pediatric neuropsychiatric conditions and may influence immune and autonomic pathways involved in postinfectious symptoms. Here we show associations between SSRI/SNRI use and long coronavirus disease (COVID)-related outcomes in a retrospective cohort of 110,955 children and adolescents with pre-existing neuropsychiatric conditions across 37 US health systems participating in the National Institutes of Health Researching COVID to Enhance Recovery consortium. SSRI/SNRI use was not associated with clinician-recorded long COVID diagnosis but showed heterogeneous associations with individual symptoms. Lower risks were observed for some symptoms, including fever, chills and hair loss, whereas higher risks were observed for neurological and systemic outcomes, including postural orthostatic tachycardia syndrome, cognitive dysfunction and fatigue. These findings suggest that antidepressant exposure may be associated with differing post-COVID symptom patterns in youth and warrant further investigation.

We aimed to assess the risk of incident autoimmune and inflammatory conditions during the post-acute period of COVID-19. Descriptive network cohort study. Electronic health records from the UK and Dutch primary care, Norwegian linked health registry, hospital records of specialist centres in Spain, France and Korea and healthcare claims from Estonia and the USA. We followed individuals between September 2020 and the latest available data from day 91 after a SARS-CoV-2 negative test (comparator) or a COVID-19 record (exposed patients, ie assessing patients during the post-acute phase). We further established a reinfection cohort (any further COVID-19 record among the exposed patients). We followed patients until an outcome, end of study period, death, day 365 or an infection (comparator only) or reinfection (exposed patients only). We assessed postural orthostatic tachycardia syndrome (POTS) diagnoses/symptoms, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnoses/symptoms, multi-inflammatory syndrome (MIS) and several autoimmune diseases (rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) and type 1 diabetes mellitus (T1DM)).Meta-analysed crude incidence rate ratios (IRRs) of outcomes after COVID-19 versus negative testing and after reinfection versus a previous COVID-19 record yield the ratios of respective absolute risks of each assessed outcome. We performed subgroup analyses by age, sex and predominant variant periods. We included 2 521 812 individuals with a first COVID-19 record, 4 233 145 with a first negative test and 135 551 with a reinfection. Age and sex were largely comparable between exposure groups with a shorter follow-up for the reinfection cohorts. After COVID-19 compared with test-negative patients and equally after reinfection compared with previous COVID-19 patients, we did not observe increased rates for all outcomes and all subgroup analyses. Counts of MIS and JIA were too small for meta-analyses. In our descriptive meta-analyses of crude IRRs among databases from various countries and settings, we did not observe increased rates of incident POTS, ME/CFS, RA, IBD, SLE and T1DM in COVID-19 versus test-negative or reinfection versus COVID-19 during the first 9 months of the post-acute phase of COVID-19 or reinfection (>90 days postinfection until month 12). Since causal interpretation cannot be made from this study, further causal research is warranted.

On December 10, 2014, the Food and Drug Administration (FDA) licensed the 9-valent human papillomavirus vaccine (9vHPV) for prevention of HPV-related cancers and genital warts. This study aimed to summarize and characterize the first decade of post-licensure surveillance reports of 9vHPV submitted to the Vaccine Adverse Event Reporting System (VAERS). We analyzed VAERS reports following 9vHPV administration in the U.S. during December 2014 through December 2024. Disproportionality analysis was conducted using the reporting odds ratio (ROR) to identify potential safety signals. Reports were categorized by sex, age, seriousness, and clinical outcomes. The VAERS received 23,499 reports following administration of 9vHPV: 46.7% were from females, 25.7% from males, and 27.6% with unreported sex. Overall, 92.5% of reports were nonserious. Syncope, dizziness, loss of consciousness and pallor were most common AEs among nonserious reports. Headache, dizziness, pain and syncope were commonly reported serious AEs. Disproportionality analysis identified six MedDRA PTs that were disproportionately reported following 9vHPV vaccination: anaphylactic shock, postural orthostatic tachycardia syndrome (POTS), dizziness postural, complex regional pain syndrome (CRPS), premature menopause and acute disseminated encephalomyelitis (ADEM). Deaths ( = 57) were rare and most lacked sufficient medical documentation to establish causality. The safety profile of 9vHPV over its first decade of use remains consistent with pre-licensure data, with most AEs being nonserious and self-limiting. Disproportionality analysis identified potential safety signals warranting further investigation but did not confirm causality. Continuous surveillance is necessary to further evaluate these rare events and ensure the ongoing safety of 9vHPV.

The effects of SARS-Cov-2 infection can extend beyond the acute phase of the illness, often described as Long COVID, post-COVID condition (PCC) or Post-acute sequelae of COVID (PASC). Post-acute sequelae (PAS) are also likely to be a problem for a small proportion of children and adolescents following influenza infection. However, there is no comprehensive ongoing data collection in Australian children and adolescents, and global data on both PCC during the SARS-Cov-2 Omicron variant period and PAS following influenza is limited. This study aims to determine the cumulative incidence of PCC in Australian children and adolescents five years after the start of the COVID-19 pandemic. Secondary aims include identifying the cumulative incidence of PAS in children and adolescents following influenza infection. This longitudinal cohort study will recruit children and adolescents aged 0-18 years in South Australia who tested positive for SARS-Cov-2 or influenza in the previous 2 months. Following consent, participants will complete an online baseline survey and then at 3, 6, and 12 months post-infection. The survey has been adapted from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) Paediatric COVID-19 follow-up survey. The survey includes validated assessment tools such as the Pediatric Quality of Life Inventory (PedsQL), Multidimensional Fatigue Scale, and the Malmö Postural Orthostatic Tachycardia Syndrome (POTS) Score questionnaire. PCC following COVID-19 and PAS following influenza infection will be identified according to an adapted World Health Organization definition of PCC in children and adolescents. This study addresses gaps in understanding PCC and PAS following influenza in children and adolescents during Omicron circulation. Whilst it is no longer feasible to prospectively compare post-acute sequelae in children and adolescents who have never had COVID-19, this design allows a comparison with another common viral infection, influenza, informing clinical management of children post-infection.

Background and objective Unexplained syncope remains a frequent and challenging clinical problem, even after guideline-directed cardiovascular and neurological evaluation. In a substantial proportion of patients, syncope remains without an identified etiology after conventional investigations, suggesting alternative underlying mechanisms. Autonomic nervous system (ANS) dysfunction plays a central role in cardiovascular regulation and has been increasingly recognized as a key contributor to unexplained syncope. ANS testing allows objective evaluation of cardiovascular autonomic reflexes, including sympathetic and parasympathetic responses to orthostatic and physiological stressors. The objective of this study was to assess autonomic profiles using standardized ANS testing in patients referred for unexplained syncope and to characterize dysautonomic patterns that may contribute to syncope mechanisms. Methods We conducted a retrospective mono-centric study including 90 consecutive adult patients referred to a tertiary autonomic unit for syncope remaining without an identified etiology after conventional evaluation between January 2024 and June 2025. All patients underwent a standardized ANS testing battery, including an active standing (orthostatic) test, a deep-breathing test, an isometric handgrip test, and a mental stress test. Demographic data, cardiovascular risk factors, clinical presentation, and ANS test results were systematically collected and analyzed. Results ANS testing identified autonomic abnormalities considered clinically relevant in a high proportion of patients with unexplained syncope despite routine conventional investigations. The most frequent findings included exaggerated vagal responses, orthostatic intolerance syndromes such as postural orthostatic tachycardia syndrome, sympathetic alpha-adrenergic dysfunction leading to orthostatic hypotension, and mixed autonomic profiles. Overlapping autonomic phenotypes were frequently observed within the same patient, underscoring the complexity of dysautonomic syncope. Conclusion ANS testing provides a high diagnostic yield in patients with syncope remaining without an identified etiology after standard evaluation by revealing clinically relevant autonomic dysregulation. Integration of ANS testing as a second-line diagnostic approach may improve etiological classification and support individualized management strategies in selected patients.

Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology. POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.

Postural orthostatic tachycardia syndrome (POTS) is defined by chronic orthostatic intolerance accompanied by an excessive increment in sinus heart rate on standing in the absence of significant orthostatic hypotension. Contemporary reviews and consensus statements appropriately frame POTS as involving autonomic regulation. Yet the bedside phenotype most often observed-marked tachycardia with preserved blood pressure-also supports a hemodynamic interpretation: an intact baroreflex driving tachycardia to defend cardiac output and cerebral perfusion when effective stroke volume or venous return is reduced. This narrative, hypothesis-driven review argues that the umbrella label 'dysautonomia' is frequently applied imprecisely in POTS and is often interpreted (by clinicians and patients) as autonomic failure. In many patients, the dominant physiology is not autonomic failure but compensatory activation in response to orthostatic stressors such as low central blood volume, venous pooling, impaired vasoconstriction, or deconditioning. When the label is over-interpreted, management can drift toward reflexive heart-rate suppression rather than mechanism-directed evaluation and treatment of the orthostatic stressor. We propose a pragmatic, cardiology-facing framework that (1) distinguishes compensatory orthostatic tachycardia from primary autonomic failure (neurogenic orthostatic hypotension), and (2) prioritizes mechanistic phenotyping within POTS (low-preload/pooling dominant, neuropathic, hyperadrenergic, immune-associated, and secondary structural/CSF-pressure contributors). This reframing does not minimize the severity of POTS; rather, it supports clearer counseling and more targeted therapy by treating tachycardia as a signal of orthostatic stress and asking what is driving it.

Postural Orthostatic Tachycardia Syndrome (POTS) is notoriously difficult to diagnose and successfully treat. POTS encompasses several different subtypes, but little research attention has focused on optimizing the diagnosis and treatment of specific subtypes. This study aims to identify variables potentially predictive of neuropathic POTS and determine which current medical therapies for POTS are most successful in the neuropathic population. Single-center retrospective review identified 382 patients diagnosed with POTS between 2018 and 2020. Diagnosis was established via the head-up tilt table test; neuropathic subtype was established via skin biopsy or quantitative sudomotor axon reflex test. Logistic regression identified variables predictive of the neuropathic subtype; Cox proportional hazard and Kaplan-Meier estimator modeling were employed to compare treatment response to medications between neuropathic and non-neuropathic patients. Patients with neuropathic POTS treated with ivabradine exhibited a median treatment response duration of 26.7 months in the neuropathic group vs. 10.7 months in the non-neuropathic group, reflecting a significantly reduced risk of treatment failure (hazard ratio = 0.273, = 0.028). No other studied treatments demonstrated different response. Of the clinical and demographic variables studied, only elevated baseline heart rate was significantly associated with the neuropathic POTS subtype, though with questionable clinical significance. Patients with neuropathic POTS may exhibit different medication treatment response compared to patients with non-neuropathic POTS, though prospective studies are needed for confirmation. Further study to identify optimal treatment regimens for different subtypes of POTS is a promising direction to improve the quality of care for patients with POTS.

Vaccination against high-risk HPV types is a key preventive measure. However, concerns regarding vaccine safety may hinder vaccination efforts. This study aims to evaluate adverse events (AEs) reported in the Vaccine Adverse Event Reporting System (VAERS) following HPV vaccination from 2006 to 2024, providing insights into its safety profile. We analyzed VAERS data, a spontaneous reporting system containing de-identified AE reports. Four disproportionality analyses (ROR, PRR, BCPNN, and MGPS) were applied, and adverse event signals were defined only when the positive criteria were simultaneously met across all four methods. Statistical analyses were performed using R software and Microsoft Excel, with a significance threshold of p < 0.05. A total of 77,909 HPV vaccine-related AE reports were analyzed, with 68.4% involving females and 48.7% affecting individuals under 18. Serious AEs accounted for 11,659 reports, with headache and fatigue being the most common. Syncope was the most frequent signal, while postural orthostatic tachycardia syndrome (POTS) exhibited the strongest signal strength. Approximately 90% of AEs occurred within 30 days post-vaccination. Among vaccine types, HPV4 had the highest number of reports, and intramuscular injection was the most common administration route. This study offers an updated pharmacovigilance assessment of adverse events reported following HPV vaccination, highlighting reported patterns and statistical signals that may warrant further investigation.

A significant number of physicians are unclear of the vast clinical manifestations of dysautonomia and imbalance of the autonomic nervous system, specifically the parasympathetic and sympathetic nervous systems. The major obstacle has been an inability to determine the mechanism of action as well as multisystem dysfunction and a lack of clear-cut testing. Dysautonomia, a pathophysiological malfunction of the sympathetic and parasympathetic nerves in our bodies, can present as altered clinical functions of heart rate (tachycardia/bradycardia), altered breathing patterns, blood pressure (hypertension/hypotension), sweating, digestion, syncope, etc. These symptoms have caused specialists to miss this diagnosis because of relative nonspecificity. Our current analysis of patients demonstrates significant delays in diagnosis, misdiagnosis, and the development of chronic syndromes because of the above. We demonstrate that monitoring of heart rate and blood pressure with changes in position and respiration can be easily and quickly performed without orthostatic stress and can demonstrate the entities of sympathetic withdrawal, cholinergic excessive aspects as well as tachycardia, blood pressure dips with posture, etc. This analysis takes less than an hour without the need for injections or medication, thus more quickly informing the cardiologist/neurologist of the correct diagnosis. We will attempt to demystify these issues so that clinicians and the scientific community will have a better understanding of this entity and consider a diagnosis of dysautonomia earlier in the differential diagnostic process and start treatment approaches sooner.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating disorder characterized by excessive increases in heart rate upon standing and poor orthostatic tolerance. Impairments in large artery, endothelial, and venous function may collectively, or individually, result in excessive blood pooling and impaired venous return, or other inadequate vascular response to standing, thus contributing to POTS. Herein, we tested the hypothesis that patients with POTS would exhibit reduced large artery stiffness, enhanced endothelial function, and greater lower limb venous pooling while standing, compared with healthy controls. Fourteen participants with a clinical diagnosis of POTS and 15 age-matched controls (all females; median age [interquartile range]; 21 [19-37] yr, = 0.769) were recruited. Central arterial stiffness was determined using carotid-femoral pulse wave velocity (cfPWV; SphygmoCor). Endothelial function was assessed using brachial artery flow-mediated dilation (FMD) following a 5-min forearm occlusion at 200 mmHg. Functional measures of calf venous volume and filling time (90% maximal venous filling) were acquired (air plethysmography) while standing. cfPWV was increased in people with POTS [(means ± SD) 5.5 ± 0.9 vs. 4.8 ± 0.4, = 0.031], whereas FMD was not different between groups ( = 0.854). During standing, calf venous volume was 29% greater in people with POTS ( = 0.048), and venous filling time was almost twice as long (404 ± 199 vs. 207 ± 99 s; = 0.003). These findings indicate that people with POTS exhibit increased central arterial stiffness, preserved endothelial function, and increased calf venous filling during standing. Such differences in lower limb venous filling dynamics on standing likely contribute to the orthostatic intolerance that characterizes POTS. Females with POTS and age-matched healthy controls underwent assessments of central arterial stiffness, endothelial function, and calf distensibility. Pulse wave velocity was higher in people with POTS, but brachial artery flow-mediated dilatation was not different between groups. Standing calf volume was greater in people with POTS, and maximal filling times were twice as long, suggesting altered venous and/or microvascular function. Augmented venous pooling in patients with POTS may impair venous return and orthostatic tolerance.