Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

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.

Heart Rate Asymmetry Analysis During Head-Up Tilt Test in Healthy Men

The purpose of this study is to assess the cardiovascular system response to orthostatic stress in a group of 133 healthy men using heart rate asymmetry (HRA) methods. HRA is a feature of variability in human heart rate which is dependent upon external and internal body conditions. The initial phases of head-up tilt test (HUTT), namely, supine and tilt, were chosen as the external body affecting factors. Various calculation methods of HRA, such as Porta’s index (PI), Guzik’s index (GI), and its variance based components, were used to assess the heart rate variability (HRV) and its asymmetry. We compared 5-min ECG recordings from both supine and tilt phases of HUT test. Short-term HRA was observed in 54.1% of men in supine phase and 65.4% of men in tilt phase. The study revealed significant increase of GI (from 0.50 to 0.52, p &lt; 0.001) in the tilt phase as well as significant changes in HRV descriptors between HUTT phases. Our results showed that the variability of human heart rate and its asymmetry are sensitive to orthostatic stress. The study of short-term HRA is a potential additional tool to increase sensitivity in conditions where HUTT is a diagnostic tool, such as vasovagal syncope.

Two-Tiered Response of Cardiorespiratory-Cerebrovascular Network to Orthostatic Challenge

Dynamic interdependencies within and between physiological systems and subsystems are key for homeostatic mechanisms to establish an optimal state of the organism. These interactions mediate regulatory responses elicited by various perturbations, such as the high-pressure baroreflex and cerebral autoregulation, alleviating the impact of orthostatic stress on cerebral hemodynamics and oxygenation. The aim of this study was to evaluate the responsiveness of the cardiorespiratory-cerebrovascular networks by capturing linear and nonlinear interdependencies to postural changes. Ten young healthy adults participated in our study. Non-invasive measurements of arterial blood pressure (from that cardiac cycle durations were derived), breath-to-breath interval, cerebral blood flow velocity (BFV, recorded by transcranial Doppler sonography), and cerebral hemodynamics (HbT, total hemoglobin content monitored by near-infrared spectroscopy) were performed for 30-min in resting state, followed by a 1-min stand-up and a 1-min sit-down period. During preprocessing, noise was filtered and the contribution of arterial blood pressure was regressed from BFV and HbT signals. Cardiorespiratory-cerebrovascular networks were reconstructed by computing pair-wise Pearson-correlation or mutual information between the resampled signals to capture their linear and/or nonlinear interdependencies, respectively. The interdependencies between cardiac, respiratory, and cerebrovascular dynamics showed a marked weakening after standing up persisting throughout the sit-down period, which could mainly be attributed to strikingly attenuated nonlinear coupling. To summarize, we found that postural changes induced topological changes in the cardiorespiratory-cerebrovascular network. The dissolution of nonlinear networks suggests that the complexity of key homeostatic mechanisms maintaining cerebral hemodynamics and oxygenation is indeed sensitive to physiological perturbations such as orthostatic stress.

The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Joint Hypermobility Show Larger Cerebral Blood Flow Reductions during Orthostatic Stress Testing Than Patients without Hypermobility: A Case Control Study

Aims: An abnormal reduction in cerebral blood flow (CBF) during orthostatic stress is common in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition with more prevalent joint hypermobility than in the healthy population. As one of proposed underlying mechanisms of orthostatic intolerance in hypermobile patients is vessel laxity, reducing the normal return of blood to the heart during orthostatic stress, we hypothesized that the CBF reduction during tilt-testing would be larger in ME/CFS patients with joint hypermobility than in patients without hypermobility. Methods: In this case-control study, 100 female ME/CFS cases with joint hypermobility, who had undergone tilt-testing with CBF measurements, were compared to 100 female ME/CFS patients without joint hypermobility, matched by age and disease duration. Results: No differences in baseline characteristics were found between groups. The hypermobile patients had significantly more postural orthostatic tachycardia syndrome (POTS) during tilt testing than the non-hypermobile ones. Compared to supine CBF, the degree of CBF reduction during the tilt was significantly larger in hypermobile cases than in the non-hypermobile controls: -32 (6)% vs -23 (7)% (p<0.0001) The larger CBF reduction in hypermobile patients was not only present in POTS patients: -33 (6)% vs -24 (4)%, but also in patients with a normal heart rate and blood pressure response to tilt testing: -31 (6)% vs -22 (9)%: (both p<0.0001). Conclusions: ME/CFS patients with joint hypermobility syndromes have larger CBF reductions during orthostatic stress testing than patients without hypermobility. This larger CBF reduction is independent of the heart rate and blood pressure results of the orthostatic stress test.