Category: Exercise

Chronic Fatigue Associated with Post-COVID Syndrome versus Transient Fatigue Caused by High-Intensity Exercise: Are They Comparable in Terms of Vascular Effects?

Abstract:

Purpose: The pathophysiology of chronic fatigue associated with post-COVID syndrome is not well recognized. It is assumed that this condition is partly due to vascular dysfunction developed during an acute phase of infection. There is great demand for a diagnostic tool that is able to clinically assess post-COVID syndrome and monitor the rehabilitation process.

Patients and methods: The Flow Mediated Skin Fluorescence (FMSF) technique appears uniquely suitable for the analysis of basal microcirculatory oscillations and reactive hyperemia induced by transient ischemia. The FMSF was used to measure vascular circulation in 45 patients with post-COVID syndrome. The results were compared with those for a group of 26 amateur runners before and after high-intensity exercise as well as for a control group of 32 healthy age-matched individuals.

Results: Based on the observed changes in the NOI (Normoxia Oscillatory Index) and RHR (Reactive Hyperemia Response) parameters measured with the FMSF technique, it was found that chronic fatigue associated with post-COVID syndrome is comparable with transient fatigue caused by high-intensity exercise in terms of vascular effects, which are associated with vascular stress in the macrocirculation and microcirculation. Acute and chronic fatigue symptomatology shared similarly altered changes in the NOI and RHR parameters and both can be linked to calcium homeostasis modification.

Conclusion: The NOI and RHR parameters measured with the FMSF technique can be used for non-invasive clinical assessment of post-COVID syndrome as well as for monitoring the rehabilitation process.

Source: Chudzik M, Cender A, Mordaka R, Zielinski J, Katarzynska J, Marcinek A, Gebicki J. Chronic Fatigue Associated with Post-COVID Syndrome versus Transient Fatigue Caused by High-Intensity Exercise: Are They Comparable in Terms of Vascular Effects? Vasc Health Risk Manag. 2022 Sep 6;18:711-719. doi: 10.2147/VHRM.S371468. PMID: 36097586; PMCID: PMC9464031.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464031/ (Full text)

Diminished Cardiopulmonary Capacity During Post-Exertional Malaise

Abstract:

Reduced functional capacity and post-exertional malaise following physical activity are hallmark symptoms of Chronic Fatigue Syndrome (CFS). That these symptoms are often delayed may explain the equivocal results for clinical cardiopulmonary exercise testing with CFS patients. The reproducibility of VO2 max in healthy subjects is well documented. This may not be the case with CFS due to delayed recovery symptoms.

Purpose: To compare results from repeated exercise tests as indicators of post-exertional malaise in CFS.

Methods: Peak oxygen consumption (VO2 peak), percentage of predicted peak heart rate (HR%), and VO2 at anaerobic threshold (AT), were compared between six CFS patients and six control subjects for two maximal exercise tests separated by 24 hours.

Results: Multivariate analysis showed no significant differences between control and CFS, respectively, for test 1: VO2 peak (28.4 ± 7.2 ml/ kg/min; 26.2 ± 4.9 ml/kg/min), AT (17.5 ± 4.8 ml/kg/min; 15.0 ± 4.9 ml/ kg/min) or HR% (87.0 ± 25.4%; 94.8 ± 8.8%). However, for test 2 the CFS patients achieved significantly lower values for both VO2 peak (28.9 ± 8.0 ml/kg/min; 20.5 ± 1.8 ml/kg/min, p = 0.031) and AT (18.0 ± 5.2 ml/kg/min; 11.0 ± 3.4 ml/kg/min, p = 0.021). HR% was not significantly different (97.6 ± 27.2%; 87.8 ± 9.3%, p = 0.07). A follow-up classification analysis differentiated between CFS patients and controls with an overall accuracy of 92%.

Conclusion: In the absence of a second exercise test, the lack of any significant differences for the first test would appear to suggest no functional impairment in CFS patients. However, the results from the second test indicate the presence of a CFS related post-exertional malaise. It might be concluded then that a single exercise test is insufficient to demonstrate functional impairment in CFS patients. A second test may be necessary to document the atypical recovery response and protracted malaise unique to CFS.

Source: J. Mark Vanness, Christopher R. Snell & Staci R. Stevens (2007) Diminished Cardiopulmonary Capacity During Post-Exertional Malaise, Journal of Chronic Fatigue Syndrome, 14:2, 77-85, DOI: 10.1300/J092v14n02_07

Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With Fatiguing Health Conditions – A Case Series

Abstract:

Purpose: Measurements obtained during maximal cardiopulmonary exercise testing (CPET) demonstrate high test–retest reliability, which indicates low error variance. However, measurements obtained from people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may depart from typically observed high reproducibility, which could represent functionally relevant biological variability that is characteristic of the underlying pathophysiology. The purpose of this case series was to document individual experiences with test–retest variability in CPET measurements in individuals with ME/CFS compared with other fatiguing health conditions.

Methods: In this case series, 6 women matched for age and body mass index underwent 2 maximal CPETs spaced 24 hours apart. Clients comprised 1 sedentary individual without fatigue, 1 active individual without fatigue, 1 individual with multiple sclerosis (MS), 1 individual diagnosed with HIV, 1 individual with ME/CFS and low maximal volume of oxygen consumed (VO2max), and 1 high-functioning individual with ME/CFS and high VO2max. Percent change in CPET measurements between tests was calculated for each client.

Results: Nondisabled clients and clients with MS and HIV reproduced or improved in their volume of oxygen consumed (VO2), workload (WL), heart rate (HR), and minute ventilation (VE) at ventilatory anaerobic threshold (VAT) and at peak exercise (except peak WL and VE for the individual with HIV). Neither individual with ME/CFS reproduced VO2, WL, HR, or VE at VAT within literature estimates.

Conclusions: Measurements during CPET for individual patients may relate to potential condition-specific deficits in cardiac, pulmonary, and metabolic functioning.

Source: Larson, Benjamin PT, DPT1; Davenport, Todd E. PT, DPT, MPH, OCS2,3; Stevens, Staci R. MA3; Stevens, Jared BS3; Van Ness, J. Mark PhD3,4; Snell, Christopher R. PhD3. Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With Fatiguing Health Conditions: A Case Series. Cardiopulmonary Physical Therapy Journal: October 2019 – Volume 30 – Issue 4 – p 145-152 doi: 10.1097/CPT.0000000000000100 https://journals.lww.com/cptj/Abstract/2019/10000/Reproducibility_of_Measurements_Obtained_D%20uring.4.aspx

Validity of 2-Day Cardiopulmonary Exercise Testing in Male Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Among the main characteristics of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are effort intolerance along with a prolonged recovery from exercise and post-exertional exacerbation of ME/CFS symptoms. The gold standard for measuring the severity of physical activity intolerance is cardiopulmonary exercise testing (CPET). Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients. A consecutive day CPET protocol has shown a difference on day 2 in ME/CFS patients in contrast to sedentary controls. Because of the low number of male ME/CFS patients in the published literature, and because of a possible gender difference in the clinical phenotype, the aim of this study was to examine whether the response to a 2-day CPET protocol in a larger sample of male ME/CFS patients was similar to that observed in females.

Methods: From 77 male patients, 25 male ME/CFS patients fulfilled the criteria of a 2-day CPET protocol for analysis. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analysed using a paired t-test.

Results: Baseline characteristics of the group were as follows. Mean age was 44 (12) years, mean BMI was 27.1 (4.4) kg/m2. Median disease duration was 10 years (IQR 7 – 13). Heart rate, systolic and diastolic blood pressure at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between <0.005 and <0.0001). All patients experienced a deterioration of performance on CPET2 as measured by the predicted and actual VO2 and workload at peak exercise and ventilatory threshold.

Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a consecutive day CPET. These results are similar to published results in female ME/CFS populations.

Source:

 

Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Background: Repeated maximal exercise separated by 24 hours may be useful in identifying possible objective markers in people with ME/CFS that are not present in healthy controls.

Aim: We aimed to synthesise studies in which the test-to-retest (24 hours) changes in VO2 and work rate have been compared between people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and controls.

Methods: Seven databases (CINAHL, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus and MEDLINE) were searched. Included studies were observational studies that assessed adults over the age of 18 years with a clinical diagnosis of ME/CFS compared to healthy controls. The methodological quality of included studies was assessed using the Systematic Appraisal of Quality for Observational Research critical appraisal framework. Data from included studies were synthesised using a random effects meta-analysis.

Results: The pooled mean decrease in peak work rate (five studies), measured at retest, was greater in ME/CFS by −8.55 (95% CI −15.38 to –1.72) W. The pooled mean decrease in work rate at anaerobic threshold (four studies) measured at retest was greater in ME/CFS by −21 (95%CI −38 to −4, tau = 9.8) W. The likelihood that a future study in a similar setting would report a difference in work rate at anaerobic threshold which would exceed a minimal clinically important difference (10 W) is 78% (95% CI 40%–91%).

Conclusion: Synthesised data indicate that people with ME/CFS demonstrate a clinically significant test–retest reduction in work rate at the anaerobic threshold when compared to apparently healthy controls.

Source: John Derek Franklin & Michael Graham (2022) Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2108628  https://www.tandfonline.com/doi/full/10.1080/21641846.2022.2108628 (Full text)

Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19

Abstract:

COVID-19 is not only a short-term infection, as patients (pts) recovering from SARS-CoV-2 infection complain of persisting symptoms, which may lead to chronic fatigue syndrome. There is currently no evidence that nutritional supplements can assist in the recovery of pts with chronic fatigue syndrome. 1-Methylnicotinamide (1-MNA) is an endogenic substance that is produced in the liver when nicotinic acid is metabolized. 1-MNA demonstrates anti-inflammatory and anti-thrombotic properties. Therefore, we investigated whether 1-MNA supplements could improve exercise tolerance and decrease fatigue among patients recovering from SARS-CoV-2.

Methods: The study population was composed of 50 pts who had recovered from symptomatic COVID-19. The selected pts were randomized into two groups: Gr 1 (NO-1-MNA)-without supplementation; Gr 2 (1-MNA) with 1-MNA supplementation. At the beginning of the study (Phase 0), in both groups, a 6-minute walk test (6MWT) was carried out and fatigue assessment was performed using the Fatigue Severity Scale (FSS). Both FSS and 6MWT were repeated after 1 month.

Results: A significant improvement in the mean distance covered in the 6MWT was noted at follow-up in Gr 1-MNA, compared with Gr NO-1-MNA. We also noted that in Gr 1-MNA, the 6MWT distance was significantly higher after 1 month of supplementation with 1-MNA, compared with the beginning of the study (515.18 m in Phase 0 vs. 557.8 m in Phase 1; p = 0.000034). In Gr 1-MNA, significantly more pts improved their distance in the 6MWT (23 out of 25 pts, equal to 92%), by a mean of 47 m, compared with Gr NO-1-MNA (15 of 25 pts, equal to 60%) (p = 0.0061). After one month, significantly more patients in the group without 1-MNA had severe fatigue (FSS ≥ 4) compared with the group with supplementation (Gr 1-MNA = 5 pts (20%) vs. Gr NO-1-MNA = 14pts (56%); p = 0.008).

Conclusions: 1-MNA supplementation significantly improved physical performance in a 6-min walk test and reduced the percentage of patients with severe fatigue after COVID-19. The comprehensive action of 1-MNA, including anti-inflammatory and anticoagulant effects, may be beneficial for the recovery of patients with persistent symptoms of fatigue and low tolerance to exercise after COVID-19.

Source: Chudzik M, Burzyńska M, Kapusta J. Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19. Nutrients. 2022 Jul 22;14(15):3004. doi: 10.3390/nu14153004. PMID: 35893858.  https://www.mdpi.com/2072-6643/14/15/3004/htm (Full text)

Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes?

Abstract:

A variety of rehabilitation programmes can be offered to Long COVID patients, specifically physical training. Indeed 90% of these patients reports impairments of verticalization, stability and spatial orientation, making difficult exercise in the gym. The aim of our study was to assess the effectiveness and safety of aquatic exercise techniques as part of a comprehensive rehabilitation program for patients with Long COVID.

The first of a two-stage program involved development of aquatic exercises technique, which was evaluated in 12 patients with impaired upright posture control before and after exercising by “Habilect” video gait analysis system. During the second phase, effectiveness and safety of aqua exercises were tested in water pool as part of a comprehensive rehabilitation programme conducted in 23 patients with Long COVID outcomes. Physical examination, 6-minute step test, Euro-QL-5D questionnaire, Borg scale, laser Doppler flowmetry, cardiointervalography, and spirometry were performed before and after the aquatic exercises program.

After the training with aquatic exercises, indices of deviations of the main body axes of the head and the body mass centre ameliorated, as well as direction of body movement vector decreased (p<0.05). This study demonstrated a statistically significant improvement in exercise tolerance in both groups, as measured by the 6-minute step test after rehabilitation. The comparison group averaged 236.7 metres [126; 380] (T=8, p=0.047) after the rehabilitation course and the intervention group averaged 233.71 metres [150; 320] (T=8.0, p=0.047). When tested with the Euro-QL-5D questionnaire, a post-treatment improvement was noted in the comparison group on the anxiety/depression subscale (3 [3;3] (T=0, p=0.043)).

In the intervention group, laser Doppler flowmetry revealed a statistically significant increase in microcirculation (6.36 standard units after rehabilitation) [5.54; 8.17] (T=7.0, p=0.004), and a decrease of oxidative metabolism index of 6.89 standard units. [4.76; 6.96] (T=4.0, p=0.03). No serious adverse events were reported. In conclusion, the developed aquatic exercises technique seems to contribute to recovery of impaired upright posture and motor function, normalizing the walking pattern.

Source: Lobanov AA, Irina A Grishechkina, Andronov SV, Gleb N Barashkov, Andrey I Popov, Anatoliy D Fesyun, Elena P Ivanova, Maccarone MC, Stefano Masiero. Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes? Eur J Transl Myol. 2022 Jul 14. doi: 10.4081/ejtm.2022.10698. Epub ahead of print. PMID: 35833897.  https://pubmed.ncbi.nlm.nih.gov/35833897/ (Full text: Follow link on page)

Inflammation during early post-acute COVID-19 is associated with reduced exercise capacity and Long COVID symptoms after 1 year

Abstract:

Background: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.

Methods: We performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection in the UCSF Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; NCT04362150 ) and correlated findings with previously measured biomarkers. We used logistic regression to estimate associations with PASC symptoms (dyspnea, chest pain, palpitations, and fatigue) adjusted for confounders and linear regression to estimate differences between those with and without symptoms adjusted for confounders.

Results: Out of 120 participants in the cohort, 46 participants (unselected for symptom status) had at least one advanced cardiac test performed at median 17 months following initial SARS-CoV-2 infection. Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), higher extracellular volume was associated with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/23 (57%) with cardiopulmonary symptoms or fatigue had reduced exercise capacity (peak VO 2 <85% predicted) compared to 2/16 (13%) without symptoms (p=0.008). The adjusted difference in peak VO 2 was 5.9 ml/kg/min lower (-9.6 to -2.3; p=0.002) or -21% predicted (-35 to -7; p=0.006) among those with symptoms. Chronotropic incompetence was the primary abnormality among 9/15 (60%) with reduced peak VO 2 . Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Inflammatory markers (hsCRP, IL-6, TNF-α) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO 2 more than 1 year later.

Conclusions: Cardiopulmonary symptoms and elevated inflammatory markers present early in PASC are associated with objectively reduced exercise capacity measured on cardiopulmonary exercise testing more than 1 year following COVID-19. Chronotropic incompetence may explain reduced exercise capacity among some individuals with PASC.

Clinical perspective: What is New? Elevated inflammatory markers in early post-acute COVID-19 are associated with reduced exercise capacity more than 1 year later. Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection. Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRI findings argue against myocardial dysfunction and myocarditis.

Clinical implications: Cardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or “Long COVID” should be performed in a manner that allows for assessment of heart rate response to exercise. Therapeutic trials of anti-inflammatory and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

Source: Durstenfeld MS, Peluso MJ, Kaveti P, Hill C, Li D, Sander E, Swaminathan S, Arechiga VM, Sun K, Ma Y, Zepeda V, Lu S, Goldberg SA, Hoh R, Chenna A, Yee BC, Winslow JW, Petropoulos CJ, Win S, Kelly JD, Glidden DV, Henrich TJ, Martin JN, Lee YJ, Aras MA, Long CS, Grandis DJ, Deeks SG, Hsue PY. Inflammation during early post-acute COVID-19 is associated with reduced exercise capacity and Long COVID symptoms after 1 year. medRxiv [Preprint]. 2022 Jun 1:2022.05.17.22275235. doi: 10.1101/2022.05.17.22275235. PMID: 35677073; PMCID: PMC9176659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176659/ (Full text)

Impaired Cardiac Autonomic Control in Women With Fibromyalgia Is Independent of Their Physical Fitness

Abstract:

Background/objective: Evidence has suggested abnormal cardiac autonomic responses to exercise in patients with fibromyalgia (FM). However, it is not clear whether the dysautonomia represents a reduced physical fitness rather directly related to FM pathogenesis. Thus, we aimed to verify the cardiac autonomic responses before, during, and after a maximal incremental exercise in women with FM and whether these hypothesized alterations would be dependent with their physical fitness.

Methods: This is a cross-sectional study with 23 FM women and 17 healthy women. The participants performed a maximal incremental cycling test to determine their maximal workload (Wmax) and were further matched by their Wmax (14 FM patients, Wmax: 128.6 ± 16.2 W; and 14 healthy women, Wmax: 131.9 ± 15.9 W). Beat-to-beat heart rate (HR) was continuously monitored to calculate HR variability indexes at rest, chronotropic reserve during exercise, and HR recovery.

Results: Heart rate variability indexes related to vagal modulation were significantly lower in FM patients than in healthy women (p < 0.05). The chronotropic reserve and the HR recovery at 30, 120, 180, 300, and 600 seconds after exercise were all lower in FM patients compared with those of healthy women (p < 0.05). Similar findings were found when analysis was performed using the matched physical fitness subgroup.

Conclusions: The documented cardiac autonomic abnormalities at rest, during, and after exercise in FM patients persist even when physical fitness status is taken in account. Thus, strategies to attenuate the dysautonomia in FM patients must be considered.

Source: Schamne JC, Ressetti JC, Lima-Silva AE, Okuno NM. Impaired Cardiac Autonomic Control in Women With Fibromyalgia Is Independent of Their Physical Fitness. J Clin Rheumatol. 2021 Sep 1;27(6S):S278-S283. doi: 10.1097/RHU.0000000000001518. PMID: 32826659. https://pubmed.ncbi.nlm.nih.gov/32826659/

Decreased Fatty Acid Oxidation and Altered Lactate Production during Exercise in Patients with Post-acute COVID-19 Syndrome

To the Editor:

After acute infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many individuals experience a range of symptoms including dyspnea, exercise intolerance, and chest pain commonly referred to as “post–COVID-19 syndrome” or as post-acute sequelae of SARS-CoV-2 infection (PASC) (). Exertional dyspnea and physical activity intolerance in PASC can be debilitating despite mild acute coronavirus disease (COVID-19) and normal resting pulmonary physiology and cardiac function (). There is an urgent need to understand the pathogenesis of PASC and find effective treatments. The cardiopulmonary exercise test (CPET) is commonly used to investigate unexplained exertional dyspnea; as such, it could provide insight into mechanisms of PASC. CPET data can be used to calculate rates of β-oxidation of fatty acids (FATox) and of lactate clearance, providing insight into mitochondrial function (). Fit individuals have better mitochondrial function and a higher rate of FATox during exercise than less fit individuals (). Our results suggest that patients with PASC have significant impairment in fat β-oxidation and increased blood lactate accumulation during exercise, regardless of previous comorbidities.

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Source: de Boer, E., Petrache, I., Goldstein, N. M., Olin, J. T., Keith, R. C., Modena, B., Mohning, M. P., Yunt, Z. X., San-Millán, I., & Swigris, J. J. (2022). Decreased Fatty Acid Oxidation and Altered Lactate Production during Exercise in Patients with Post-acute COVID-19 Syndrome. American journal of respiratory and critical care medicine, 205(1), 126–129. https://doi.org/10.1164/rccm.202108-1903LE  I https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865580/ (Full text)