Post-HPV-Vaccination Mast Cell Activation Syndrome: Possible Vaccine-Triggered Escalation of Undiagnosed Pre-Existing Mast Cell Disease?

For nearly a decade, case reports and series have emerged regarding dysautonomias—particularly postural orthostatic tachycardia syndrome (POTS)—presenting soon after vaccination against human papilloma virus (HPV). We too have observed a number of such cases (all following vaccination with the Gardasil product), and have found several to have detectable mast cell activation syndrome (MCAS) as well as histories suggesting that MCAS was likely present long before vaccination. We detail 11 such cases here, posing a hypothesis that HPV vaccination (at least with the Gardasil product) may have triggered or exacerbated MCAS in teenagers previously not recognized to have it. Only recently recognized, MCAS is being increasingly appreciated as a prevalent and chronic multisystem disorder, often emerging early in life and presenting with inflammatory ± allergic phenomena following from known mast cell (MC) mediator effects. There is rising recognition, too, of associations of MCAS with central and peripheral neuropathic disorders, including autonomic disorders such as POTS. Given the recognized potential for many antigens to trigger a major and permanent escalation of baseline MC misbehavior in a given MCAS patient, we hypothesize that in our patients described herein, vaccination with Gardasil may have caused pre-existing (but not yet clinically recognized) MCAS to worsen to a clinically significantly degree, with the emergence of POTS and other issues. The recognition and management of MCAS prior to vaccinations in general may be a strategy worth investigating for reducing adverse events following HPV vaccinations and perhaps even other types of vaccinations.

Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients

Background and objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Exact numbers on syncopal spells especially if they are on a weekly or even daily basis are not described. Although not a frequent phenomenon, this symptomatology is of very high burden to the patient if present. To explore whether patients with very frequent (pre)syncope spells diagnosed elsewhere with conversion or psychogenic pseudosyncope (PPS) might have another explanation of their fainting spells than behavioral psychiatric disorders, we performed a case–control study comparing ME/CFS patients with and without PPS spells. Methods and results: We performed a case–control study in 30 ME/CFS patients diagnosed elsewhere with PPS and compared them with 30 control ME/CFS patients without syncopal spells. Cases were gender, age and ME/CFS disease duration matched. Each underwent a tilt test with extracranial Doppler measurements for cerebral blood flow (CBF). ME/CFS cases with PPS had a significant larger CBF reduction at end tilt than controls: 39 (6)% vs. 25 (4)%; (p < 0.0001). Cases had more severe disease compared with controls (chi-square p < 0.01 and had a p = 0.01) for more postural orthostatic tachycardia syndrome in cases compared with controls. PETCO2 end-tilt differed also, but the magnitude of difference was smaller than compared with the CBF reduction: there were no differences in heart rate and blood pressure at either end-tilt testing period. Compared with the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 25 (5) mmHg versus 29 (4) mmHg (p < 0.005). Conclusions: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background.

Orthostatic intolerance in adults with long COVID was not associated with postural orthostatic tachycardia syndrome

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults with long COVID. Participants underwent a 3-minute active stand (AS) with Finapres NOVA, followed by a 10-minute unmedicated 70-degree head-up tilt test. 85 participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the 1st minute post-stand (mean HRnadir: 88 vs 75 bpm, P=0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR=1.09, 95% CI: 1.01-1.18, P=0.027). 22 participants had initial (iOH) and 5 classical (cOH) orthostatic hypotension, but neither correlated with OIAS. 71 participants proceeded to tilt, of which 28 had OI during tilt (OItilt). Of the 53 who had a 10-minute tilt, 7 (13%) fulfilled hemodynamic postural orthostatic tachycardia syndrome (POTS) criteria, but 6 did not report OItilt. OIAS was associated with a higher initial HR on AS, which after 1 minute equalized with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent and largely asymptomatic. ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).

Characteristics of Patients Referred to a Cardiovascular Disease Clinic for Post-Acute Sequelae of SARS-CoV-2 Infection

ABSTRACTThere is limited literature on the cardiovascular manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC). We aimed to describe the characteristics, diagnostic evaluations, and cardiac diagnoses in patients referred to a cardiovascular disease clinic designed for patients with PASC from May 2020 to September 2021. Of 126 patients, average age was 46 years (range 19-81 years), 43 (34%) were male. Patients presented on average five months after COVID-19 diagnosis. 30 (24%) patients were hospitalized for acute COVID-19. Severity of acute COVID-19 was mild in 37%, moderate in 41%, severe in 11%, and critical in 9%. Patients were also followed for PASC by pulmonology (53%), neurology (33%), otolaryngology (11%), and rheumatology (7%). Forty-three patients (34%) did not have significant comorbidities. The most common symptoms were dyspnea (52%), chest pain/pressure (48%), palpitations (44%), and fatigue (42%), commonly associated with exertion or exercise intolerance. The following cardiovascular diagnoses were identified: nonischemic cardiomyopathy (5%); new ischemia (3%); coronary vasospasm (2%); new atrial fibrillation (2%), new supraventricular tachycardia (2%); myocardial involvement (15%) by cardiac MRI, characterized by late gadolinium enhancement (LGE; 60%) or inflammation (48%). The remaining 97 patients (77%) exhibited common symptoms of fatigue, dyspnea on exertion, tachycardia, or chest pain, which we termed “cardiovascular PASC syndrome.” Three of these people met criteria for postural orthostatic tachycardia syndrome. Lower severity of acute COVID-19 was a significant predictor of cardiovascular PASC syndrome. In this cohort of patients referred to cardiology for PASC, 23% had a new diagnosis, but most displayed a pattern of symptoms associated with exercise intolerance.

Remotely Supervised Home-Based Resistance Training and Orthostatic Tolerance in Young Physically Inactive Women During COVID-19

Introduction: Orthostatic intolerance (OI) is the inability of the cardiovascular system to adequately adjust to gravity upon standing, resulting in lightheadedness or syncope. OI can be characteristic of pathology (e.g. postural orthostatic tachycardia syndrome), which disproportionately affect women, and is compounded by inactivity. Thus, we tested the effects of remotely supervised home-based, 4-week resistance training (RT) program vs. control on the orthostatic stress response of previously inactive young females using the NASA Lean Test (NLT). Methods: Systolic (SBP) and diastolic (DBP) blood pressures, and heart rate (HR) were assessed during the NLT, pre- and post-training, along with fitness and body composition in females randomized to RT or control (n=7). Results: RT improved fitness (group*intervention, p=0.047) and fat-mass (-3.4±2.9 vs. +0.3±0.7Δlbs, p=0.037) over control. The NLT significantly altered SBP, DBP, and HR (all, p<0.01). For SBP, the interaction of group*intervention approached significance (p=0.071), lowering SBP in the RT group with the intervention. In DBP, the group*intervention was not significant (p=0.558). For HR, the group*intervention interaction approached significance (p=0.066). Conclusions: In the current study, short-term remotely-supervised RT using bands tended to decrease SBP and HR during orthostatic stress in young, otherwise healthy, previously inactive females, suggesting improved health but perhaps not orthostatic tolerance.