Tag: POTS

Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options

Abstract:

With the global rollout of COVID-19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID-like syndrome following vaccination, informally called long Vax and provisionally termed post-COVID-19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies.

Our review noted that PCVS typically manifests within days to weeks post-vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small-fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long-term sequelae of myocarditis, vaccine-induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea.

We also review pathophysiological hypotheses of PCVS, focussing on the vaccine-derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.

Source: Yong SJ, Kenny TA, Halim A, Munipalli B, Alhashem YN, AlSaihati H, Al-Subaie MF, Al Kaabi NA, Al Fares MA, Garout M, Sabour AA, Alshiekheid MA, Almansour ZH, Alotaibi J, Alrasheed HA, Alamri AA, Albayat H, Alamodi AS, Tombuloglu H, Mohapatra RK, Hazazi A, Rabaan AA. Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options. Rev Med Virol. 2025 Sep;35(5):e70070. doi: 10.1002/rmv.70070. PMID: 40944962. https://pubmed.ncbi.nlm.nih.gov/40944962/

Postural orthostatic tachycardia syndrome is associated with platelet storage pool deficiency

Abstract:

Mechanisms have been postulated to explain postural orthostatic tachycardia syndrome (POTS), however, the etiology of this often debilitating disorder remains unknown. We conducted a retrospective case-control study of 181 POTS patients who exhibited/reported bleeding symptoms for a specific platelet (PL) dysfunction disorder, delta granule storage pool deficiency (δ-SPD).Patients were included only if results of blood tests for δ-SPD were available.

Electron microscopy was utilized to diagnose δ-SPD. An ELISA assay was used to determine serotonin (5HT) concentration in PLs and medical record review was employed to collect patients’ clinical symptoms.The most common bleeding symptom was easy bruising (71%) but frequent nose bleeds, heavy menstrual bleeding, and a family history of bleeding were also commonly reported. Of the patients studied, 81% were diagnosed with δ-SPD.

Our investigation of 5HT concentration extracted from PLs revealed significantly lower levels of 5HT in POTS patients when compared to that of control subjects. Our data suggest that patients with POTS have significant comorbidities including bleeding symptoms and/or family bleeding histories, and have diminished PL 5HT levels supporting the hypothesis that POTS is a low 5HT level disorder.

While we describe a significant relationship with POTS and δ-SPD, this finding does not constitute an etiology for POTS.Our results establish an additional comorbidity frequently seen in POTS that could explain a number of disparate symptoms often affecting the severity of POTS.

Source: Gunning WT 3rd, Karabin BL, Blomquist TM, Grubb BP. Postural orthostatic tachycardia syndrome is associated with platelet storage pool deficiency. Medicine (Baltimore). 2016 Sep;95(37):e4849. doi: 10.1097/MD.0000000000004849. PMID: 27631244; PMCID: PMC5402587. https://pmc.ncbi.nlm.nih.gov/articles/PMC5402587/ (Full text)

Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease characterized by exertional intolerance and fatigue which is often accompanied by muscle weakness and fatiguability. A study showed efficacy of the acetylcholinesterase inhibitor pyridostigmine on cardiac output in ME/CFS patients. Pyridostigmine is currently used off-label in ME/CFS and postural orthostatic tachycardia syndrome.

Methods: We evaluated the effect of pyridostigmine on hand grip strength in 20 patients with post-infectious ME/CFS. Hand grip strength testing was performed ten times using an electric dynamometer and was repeated after 1 h. In a second test, 30 mg of pyridostigmine was given immediately after the first measurement. Orthostatic function was assessed using a passive standing test. Neurological examination and autoantibody testing were performed to rule out a diagnosis of myasthenia gravis.

Results: All patients had reduced maximum hand grip strength with a median of 16.45 kg (IQR: 11.45 kg–22.8 kg). Hand grip strength was diminished by a median of 4.65 kg after 1 h. In contrast, 1 h after pyridostigmine administration, patients showed an improvement in maximum hand grip strength with a median increase of 2.6 kg. The maximum hand grip strength after exertion was about 1.5-fold higher with then without pyridostigmine (p = 0.01). The increase in heart rate from lying to standing was median 17 beats per minute without pyridostigmine (IQR: 13 beats per minute – 23 beats per minute) and 13 beats per minute (IQR: 9 beats per minute – 20 beats per minute) (p = 0.017) with pyridostigmine. None of the patients tested positive for myasthenia gravis specific autoantibodies.

Conclusion: Pyridostigmine exerts an immediate effect on muscle strength and orthostatic function. This may be attributed to increased acetylcholine availability at neuromuscular junctions, and its augmentation of parasympathetic tone.

Source: Schlömer Ella , Stein Elisa , Kedor Claudia , Rust Rebekka , Brock Anna , Wittke Kirsten , Scheibenbogen Carmen , Kim Laura. Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in Neuroscience, Volume 19 – 2025. DOI: 10.3389/fnins.2025.1637838 ISSN: 1662-453X https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1637838/full (Full text)

Effects of recumbent isometric yoga on the orthostatic cardiovascular response of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Our previous studies demonstrated that the regular practice of recumbent isometric yoga reduced the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Some patients with ME/CFS have postural orthostatic tachycardia syndrome (POTS); however, the effects of recumbent isometric yoga on orthostatic cardiovascular responses and whether recumbent isometric yoga improves POTS remain unknown. This pilot study was done to investigate the effect of recumbent isometric yoga on the orthostatic cardiovascular response of patients with ME/CFS.

Main body: Ten adult female patients with ME/CFS performed recumbent isometric yoga for 12 weeks. Changes in their systolic blood pressure (SBP), diastolic blood pressure (DBP), and the pulse rate (PR) during an active standing test were compared before and after the 12-week regimen. Among the 10 patients, 8 manifested a normal orthostatic response and 2 manifested POTS before the yoga intervention. Patients who manifested a normal orthostatic response before yoga also manifested the normal orthostatic pattern after the yoga intervention. In contrast, the two patients who manifested POTS before the regimen showed a normal orthostatic response after completing the yoga intervention.

Conclusions: This study found that the patients who manifested POTS and performed recumbent isometric yoga for 12 weeks had a reduced increase in PR after standing up. This pilot study suggests that recumbent isometric yoga would be useful as an adjunctive nonpharmacological intervention for improving POTS in patients with ME/CFS. This finding should be confirmed in a larger number of cases.

Source: Oka T, Lkhagvasuren B. Effects of recumbent isometric yoga on the orthostatic cardiovascular response of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Biopsychosoc Med. 2025 Sep 1;19(1):16. doi: 10.1186/s13030-025-00336-w. PMID: 40890788. https://bpsmedicine.biomedcentral.com/articles/10.1186/s13030-025-00336-w (Full text)

Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries

Abstract:

Purpose. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition with no single, uniformly effective pharmacologic therapy. Dysautonomic features like orthostatic intolerance and postural tachycardia syndrome are common features in ME/CFS, severely affecting the patient´s quality-of-life. Intermittent saline infusion may reduce symptoms associated with dysautonomia, but this has not been tested scientifically in patients with ME/CFS.

In this case-series, 22 patients with ME/CFS and signs of dysautonomia and/or hypovolemia were treated every third week over 9 weeks with intravenous saline (9 mg/mL NaCl), using standard aseptic technique. Symptoms were monitored throughout the treatment regime, and a follow-up evaluation was conducted.

Results. At treatment start, patients were predominantly female (95%), at mean age 46 ± 10 years, and with a mean body hydration percentage of 48 ± 6. Self-reported health status revealed an overall symptom score of 47 ± 13 on a 0-96 scale, a median POTS score of 64 (IQR 16) on a 0-120 scale, and poor measures of quality-of-life (median 25 IQR 25, on a 0-100 scale) and abilityto-work (median 0, IQR 26, on a 0-100 scale). Following 9 weeks of intermittent saline infusion (mean volume 1600 ± 360 mL), self-reported composite symptom score, quality-of-life and POTS-related symptoms improved significantly (all p<0.001), as did ability-to-work (p<0.05).

Our data derived from a non-controlled case-series indicate health benefits from volume loading with intermittent infusion of saline among patients with ME/CFS, which may stimulate further studies on various forms of intravenous volume loading to patients with ME/CFS and dysautonomia.

Source: Per Sjogren, Helena Huhmar, Bo Christer Bertilson, Björn A Bragée, Olli Polo. Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries. Front. Neurol., Sec. Autonomic Disorders, Volume 16 – 2025 | doi: 10.3389/fneur.2025.1601599 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1601599/abstract

The Relation Between Cardiac Output and Cerebral Blood Flow in ME/CFS Patients with a POTS Response During a Tilt Test

Abstract:

Background/Objectives: Orthostatic intolerance is prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), CBF is regulated complexly, and cardiac output (CO) is an important determinant of CBF. A review in HC showed that a 30% reduction in CO results in a 10% reduction in CBF. In contrast, we showed in ME/CFS patients with a normal HR (HR) and blood pressure response during a tilt test that CO and CBF decreased to a similar extent. The relation between CO and CBF in ME/CFS patients with postural orthostatic tachycardia syndrome (POTS) is unknown.

Therefore, the aim of this study is to assess the relation between CBF and CO, in ME/CFS patients with POTS. The methods used in this retrospective study analyze this relation in a large group of patients. We also analyzed the influence of clinical data. A total of 260 ME/CFS patients with POTS underwent tilt testing with measurements of HR, BP, CBF, CO, and end-tidal PCO2. We measured CBF using extracranial Doppler flow velocity and vessel diameters obtained with a General Electric echo system, and suprasternal aortic flow velocities were measured using the same device. We recorded end-tidal PCO2 using a Nonin Lifesense device.

Results: End-tilt HR and the HR increase were significantly higher in the patients with a %CO reduction ≥ -15% than in the other group. End-tilt CO was higher and the %CO reduction was lower in patients with %CO reduction ≥ -15% than in the other group. CBF data (supine, end-tilt and the %CBF reduction) were not different between the two patient groups. The use of HR increases and %SV reductions were not as discriminative as the %CO reduction.

Conclusions: In ME/CFS patients with POTS during tilt testing with measurements of both the CO and the CBF, two different patterns were observed: (1) appr. two-thirds of patients had an almost 1:1 relation between the %CBF reduction and the %CO reduction. (2) Appr. one-third of patients showed a limited reduction in CO together with a substantial increase in HR. In these patients, there was no relation between the CO and CBF reduction. These data suggest the presence of a hyperadrenergic response.

Source: van Campen CLMC, Visser FC. The Relation Between Cardiac Output and Cerebral Blood Flow in ME/CFS Patients with a POTS Response During a Tilt Test. J Clin Med. 2025 May 22;14(11):3648. doi: 10.3390/jcm14113648. PMID: 40507411. https://www.mdpi.com/2077-0383/14/11/3648 (Full text)

Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research

Abstract:

The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients’ symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients’ psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan’s (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person’s experiences with illness.

We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia.

Consistent with Linehan’s theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay.

Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Source: Bontempo AC, Bontempo JM, Duberstein PR. Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research. Psychol Bull. 2025 Apr;151(4):399-427. doi: 10.1037/bul0000473. PMID: 40310228. https://psycnet.apa.org/fulltext/2026-10154-001.html (Full text)

Stellate Ganglion Block reduces symptoms of SARS-CoV-2-induced ME/CFS: A prospective cohort pilot study

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition characterized by fatigue, orthostatic intolerance (OI), post-exertional malaise (PEM) and unrefreshing sleep. Our previous work has shown that modulating the autonomic nervous system can alleviate symptoms of Long COVID, which shares striking similarities with ME/CFS.

Objective: Determine the effect of stellate ganglion block (SGB) on symptoms of ME/CFS.

Methods: Subjects who met the WHO criteria for Long COVID and the Institute of Medicine criteria for ME/CFS were treated with sequential bilateral SGBs separated by 18–24 hours for three consecutive weeks (n = 10). At baseline, and at 2-weeks and 2-months post-treatment, we collected subjective assessments (SF-36 and DSQ2) of symptoms, objective assessments of orthostatic intolerance and cognitive performance, and saliva to measure morning cortisol. During the entire study period, a wearable device collected physiological data several nights a week to measure sleep parameters.

Results: DSQ2 measures of PEM, Unrefreshing Sleep, Cognitive Impairment, and OI improved significantly following treatment. SF-36 measures of Vitality, Physical Function, and Social Function improved significantly following treatment. Objective symptoms of POTS associated with infectious onset resolved following treatment. Objective measures of cognitive impairment were reduced following treatment, most notably in the areas of Immediate and Delayed Recognition. Morning cortisol and measures of sleep architecture did not change significantly following treatment.

Conclusions: Symptoms of ME/CFS were reduced after treatment with SGBs in this small prospective cohort pilot study. Given the lack of FDA-approved treatments for ME/CFS, replication of results in a large clinical trial is warranted.

Source: Duricka, D. L., & Liu, L. D. (2025). Stellate Ganglion Block reduces symptoms of SARS-CoV-2-induced ME/CFS: A prospective cohort pilot study. Fatigue: Biomedicine, Health &amp; Behavior, 13(2), 97–114. https://doi.org/10.1080/21641846.2025.2455876 https://www.tandfonline.com/doi/full/10.1080/21641846.2025.2455876#d1e276 (Full text)

Two Different Hemodynamic Responses in ME/CFS Patients with Postural Orthostatic Tachycardia Syndrome During Head-Up Tilt Testing

Abstract:

Introduction: While the diagnosis of postural orthostatic tachycardia syndrome (POTS) is based on heart rate (HR) and blood pressure (BP) criteria, the pathophysiology of POTS is not fully understood as multiple pathophysiological mechanisms have been recognized. Also, cardiac function, being dependent on preload, afterload, contractility, and HR, has not been properly studied. Preload and contractility changes can be inferred from stroke volume index (SVI) changes during a tilt test. Afterload plays a minor role in POTS as a normal BP response is a prerequisite for POTS. Therefore, we analyzed the HR-SVI relation during a tilt test in myalgic encephalomyelitis (ME/CFS) patients with POTS and compared the data with ME/CFS patients with a normal HR-BP response and with that of healthy controls (HC).

Material and Methods: In ME/CFS patients with either POTS (n = 233) or a normal HR-BP response (n = 507) and healthy controls (n = 48), we measured SVI (by suprasternal echo), HR, and BP during the tilt.

Results: In all ME/CFS patients, the decrease in SVI was larger compared to HC. In patients with a normal HR-BP response and in POTS patients with a HR increase between 30-39 bpm, there was an inverse relationship between the HR increase and SVI decrease during the tilt, compatible with increased venous pooling. In POTS patients with a HR increase ≥40 bpm, this inverse relation was lost, and SVI changes were significantly less compared to POTS patients with a HR increase between 30-39 bpm, suggestive of a hyperadrenergic response.

Conclusions: In ME/CFS patients with POTS, two different hemodynamic profiles can be observed: in patients with a limited HR increase, mainly increased venous pooling is observed, while in patients with a large (≥ 40 bpm) HR increase the data are suggestive of a hyperadrenergic response. These two different profiles may have different therapeutic implications.

Source: van Campen CLMC, Rowe PC, Visser FC. Two Different Hemodynamic Responses in ME/CFS Patients with Postural Orthostatic Tachycardia Syndrome During Head-Up Tilt Testing. J Clin Med. 2024 Dec 18;13(24):7726. doi: 10.3390/jcm13247726. PMID: 39768649. https://www.mdpi.com/2077-0383/13/24/7726 (Full text)

Patient-Reported Treatment Outcomes in ME/CFS and Long COVID

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are persistent multi-system illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments are invaluable for guiding management strategies in patient care and generating new avenues for research. Here, we present the results of an ME/CFS and Long COVID treatment survey with responses from 3,925 patients.

We assessed the experiences of these patients with more than 150 treatments, as well as their demographics, symptoms, and comorbidities. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of Long COVID reported post-exertional malaise (PEM). Treatments with the greatest perceived benefits were identified, which had varied effects on different core symptoms.

In addition, treatment responses were significantly correlated (R² = 0.68) between the two patient groups. Patient subgroups with distinct profiles of symptoms and comorbidities showed varied responses to treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants.

This study underscores the symptomatic and therapeutic similarities between ME/CFS and Long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. Insights from patient-reported experiences, in the absence of approved treatments, provide urgently needed real-world evidence for targeted therapies in patient care and for developing future clinical trials.

Source: Martha Eckey, Peng Li, Braxton Morrison, Ronald W Davis, Wenzhong Xiao. Patient-Reported Treatment Outcomes in ME/CFS and Long COVID. medRxiv 2024.11.27.24317656; doi: https://doi.org/10.1101/2024.11.27.24317656 https://www.medrxiv.org/content/10.1101/2024.11.27.24317656v1.full-text (Full text)