Factors Associated with Fatigue in COVID-19 ICU Survivors.

PURPOSE: Approximately 30% of people infected with COVID-19 require hospitalization and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial. METHODS: Fifty-nine patients [38-78 yr] hospitalized in ICU for COVID-19 infection for 32 [6-80] days including 23 [3-57] days of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 days after discharge and was dedicated to questionnaires, blood sampling and cardiopulmonary exercise testing, while measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 days later. RESULTS: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non- fatigued (i.e. 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 l vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in one second, respectively) and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82 ± 14% vs 91 ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression and quality of life (p < 0.05). CONCLUSIONS: COVID-19 survivors showed altered respiratory function 4 to 8 weeks after discharge, that was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e. sleep satisfaction, quality of life or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue.

Reliability of Corticospinal and Motoneuronal Excitability Evaluation During Unfatiguing and Fatiguing Cycling Exercise.

INTRODUCTION: Central nervous system excitability depends on the task performed, muscle group solicited, and contraction type. However, little is known on corticospinal and motoneuronal excitability measured during locomotor exercise. This study aimed at determining the reliability of motor-evoked potentials (MEP) and thoracic motor-evoked potentials (TMEP) in dynamic mode during unfatiguing and fatiguing cycling exercise. METHODS: Twenty-two participants completed four visits. Visit 1 comprised familiarization and a maximal incremental test to determine maximal power output (Wmax). The remaining visits encompassed unfatiguing evaluations, which included 8 brief bouts of moderate (50% Wmax) and high intensity cycling (80% Wmax). In each bout, a set of two TMEPs, five MEPs and one M-max were obtained. Subsequently, a fatiguing exercise to exhaustion at 80% Wmax was performed, with four sets of measurements 3 min through the exercise and 4 additional sets at exhaustion, both measured at 50% Wmax. RESULTS: Intraclass correlation coefficients (ICCs) for 5, 10, 15 and 20 MEP·Mmax-1 revealed excellent reliability at both intensities and during fatiguing exercise (ICC ≥ 0.92). TMEP·Mmax-1 showed ICCs ≥0.82 for moderate and high intensity, and it was not affected by fatigability. Overall standard error of measurement was 0.090 [0.083, 0.097] for MEP·Mmax-1 and 0.114 [0.105, 0.125] for TMEP·Mmax-1. A systematic bias associated to the number of stimulations, especially at high intensity, suggested the evaluation itself may be influenced by fatigability. A mean reduction of 8% was detected in TMEP·Mmax-1 at exhaustion. CONCLUSIONS: Motoneuronal and corticospinal excitability measured in dynamic mode presented good to excellent reliability in unfatiguing and fatiguing exercise. Further studies inducing greater fatigability must be conducted to assess the sensitivity of central nervous system excitability during cycling.

Alteration of skeletal muscle energy metabolism assessed by 31 P MRS in clinical routine: Part 2. Clinical application.

In this second part of a two-part paper, we intend to demonstrate the impact of the previously proposed advanced quality control pipeline. To understand its benefit and challenge the proposed methodology in a real scenario, we chose to compare the outcome when applying it to the analysis of two patient populations with significant but highly different types of fatigue: COVID-19 and multiple sclerosis (MS). 31 P-MRS was performed on a 3 T clinical MRI, in 19 COVID-19 patients, 38 MS patients, and 40 matched healthy controls. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Long and short TR acquisitions were also made at rest for T1 correction. The advanced data quality control pipeline presented in Part 1 is applied to the selected patient cohorts to investigate its impact on clinical outcomes. We first used power and sample size analysis to estimate objectively the impact of adding the quality control score (QCS). Then, comparisons between patients and healthy control groups using the validated QCS were performed using unpaired t tests or Mann-Whitney tests (p < 0.05). The application of the QCS resulted in increased statistical power, changed the values of several outcome measures, and reduced variability (standard deviation). A significant difference was found between the T1PCr and T1Pi values of MS patients and healthy controls. Furthermore, the use of a fixed correction factor led to systematically higher estimated concentrations of PCr and Pi than when using individually corrected factors. We observed significant differences between the two patient populations and healthy controls for resting [PCr]-MS only, [Pi ], [ADP], [H2 PO4 - ], and pH-COVID-19 only, and post-exercise [PCr], [Pi ], and [H2 PO4 - ]-MS only. The dynamic indicators τPCr , τPi , ViPCr , and Vmax were reduced for COVID-19 and MS patients compared with controls. Our results show that QCS in dynamic 31 P-MRS studies results in smaller data variability and therefore impacts study sample size and power. Although QCS resulted in discarded data and therefore reduced the acceptable data and subject numbers, this rigorous and unbiased approach allowed for proper assessment of muscle metabolites and metabolism in patient populations. The outcomes include an increased metabolite T1 , which directly affects the T1 correction factor applied to the amplitudes of the metabolite, and a prolonged τPCr , indicating reduced muscle oxidative capacity for patients with MS and COVID-19.

Alteration of skeletal muscle energy metabolism assessed by phosphorus-31 magnetic resonance spectroscopy in clinical routine, part 1: Advanced quality control pipeline.

Implementing a standardized phosphorus-31 magnetic resonance spectroscopy (31 P-MRS) dynamic acquisition protocol to evaluate skeletal muscle energy metabolism and monitor muscle fatigability, while being compatible with various longitudinal clinical studies on diversified patient cohorts, requires a high level of technicality and expertise. Furthermore, processing data to obtain reliable results also demands a great degree of expertise from the operator. In this two-part article, we present an advanced quality control approach for data acquired using a dynamic 31 P-MRS protocol. The aim is to provide decision support to the operator to assist in data processing and obtain reliable results based on objective criteria. We present here, in part 1, an advanced data quality control (QC) approach of a dynamic 31 P-MRS protocol. Part 2 is an impact study that will demonstrate the added value of the QC approach to explore data derived from two clinical populations that experience significant fatigue, patients with coronavirus disease 2019 and multiple sclerosis. In part 1, 31 P-MRS was performed using 3-T clinical MRI in 175 subjects from clinical and healthy control populations conducted in a University Hospital. An advanced data QC score (QCS) was developed using multiple objective criteria. The criteria were based on current recommendations from the literature enriched by new proposals based on clinical experience. The QCS was designed to indicate valid and corrupt data and guide necessary objective data editing to extract as much valid physiological data as possible. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Using QCS enabled rapid identification of subjects with data anomalies, allowing the user to correct the data series or reject them partially or entirely, as well as identify fully valid datasets. Overall, the use of the QCS resulted in the automatic classification of 45% of the subjects, including 58 participants who had data with no criterion violation and 21 participants with violations that resulted in the rejection of all dynamic data. The remaining datasets were inspected manually with guidance, allowing acceptance of full datasets from an additional 80 participants and recovery phase data from an additional 16 subjects. Overall, more anomalies occurred with patient data (35% of datasets) compared with healthy controls (15% of datasets). In conclusion, the QCS ensures a standardized data rejection procedure and rigorous objective analysis of dynamic 31 P-MRS data obtained from patients. This methodology contributes to efforts made to standardize 31 P-MRS practices that have been underway for a decade, with the goal of making it an empowered tool for clinical research.

A Comprehensive Evaluation of Multiple Sclerosis-Related Fatigue with a Special Focus on Fatigability.

INTRODUCTION: Fatigue is the most common and disabling symptom in multiple sclerosis (MS), being reported by 55% to 78% of patients with MS (PwMS). Etiology of MS-related fatigue remains poorly understood, but an increased neuromuscular fatigability (i.e., greater loss of torque during exercise) could contribute to this phenomenon. This study aimed to characterize the correlates of MS-related fatigue in PwMS using a comprehensive group of physiological and psychosocial measures, with a particular focus on fatigability. METHODS: Forty-two relapsing-remitting PwMS and 20 healthy subjects were recruited. PwMS were assigned in two groups (high (HF) and low (LF) fatigue) based on two fatigue questionnaires (Fatigue Severity Scale and Modified Fatigue Impact Scale). The main outcomes of this study are derived from incremental cycling completed to task failure (i.e., inability to pedal around 60 rpm). Maximal voluntary contraction (MVC), rating of perceived exertion, and central and peripheral parameters measured using transcranial magnetic and peripheral nerve stimulation were assessed in the knee extensor muscles before, during, and after the fatiguing task. Other potential correlates of fatigue were also tested. RESULTS: MVC torque decreased to a greater extent for the HF group than LF group after the third common stage of the incremental fatiguing exercise (-15.7% ± 6.6% vs -5.9% ± 13.0%, P < 0.05), and this occurred concurrently with a higher rating of perceived exertion for HF (11.8 ± 2.5 vs 9.3 ± 2.6, P < 0.05). Subjective parameters (depression, quality of life) were worse for HF compared with LF and healthy subjects ( P < 0.001). Moreover, MVC torque loss at the final common stage and maximal heart rate explained 29% of the variance of the Modified Fatigue Impact Scale. CONCLUSIONS: These results provide novel insight into the relationship between MS-related fatigue and fatigability among PwMS. The HF group exhibited greater performance fatigability, likely contributing to a higher perceived exertion than the LF group when measured during a dynamic task.

Elite vs. Experienced Male and Female Trail Runners: Comparing Running Economy, Biomechanics, Strength, and Power.

ABSTRACT: Besson, T, Pastor, FS, Varesco, G, Berthet, M, Kennouche, D, Dandrieux, P-E, Rossi, J, and Millet, GY. Elite vs. experienced male and female trail runners: comparing running economy, biomechanics, strength, and power. J Strength Cond Res 37(7): 1470-1478, 2023-The increased participation in trail running (TR) races and the emergence of official international races have increased the performance level of the world best trail runners. The aim of this study was to compare cost of running (Cr) and biomechanical and neuromuscular characteristics of elite trail runners with their lower level counterparts. Twenty elite (10 females; ELITE) and 21 experienced (10 females; EXP) trail runners participated in the study. Cr and running biomechanics were measured at 10 and 14 km·h-1 on flat and at 10 km·h-1 with 10% uphill incline. Subjects also performed maximal isometric voluntary contractions of knee and hip extensors and knee flexors and maximal sprints on a cycle ergometer to assess the power-torque-velocity profile (PTVP). Athletes also reported their training volume during the previous year. Despite no differences in biomechanics, ELITE had a lower Cr than EXP (p < 0.05). Despite nonsignificant difference in maximal lower-limb power between groups, ELITE displayed a greater relative torque (p < 0.01) and lower maximal velocity (p < 0.01) in the PTVP. Females displayed shorter contact times (p < 0.01) compared with males, but no sex differences were observed in Cr (p > 0.05). No sex differences existed for the PTVP slope, whereas females exhibited lower relative torque (p < 0.01) and velocity capacities (p < 0.01) compared with males. Although not comprehensively assessing all determining factors of TR performance, those data evidenced level and sex specificities of trail runners in some factors of performance. Strength training can be suggested to lower level trail runners to improve Cr and thus TR performance.

Elite Road vs. Trail Runners: Comparing Economy, Biomechanics, Strength, and Power.

ABSTRACT: Sabater Pastor, FS, Besson, T, Berthet, M, Varesco, G, Kennouche, D, Dandrieux, P-E, Rossi, J, and Millet, GY. Elite road vs. trail runners: comparing economy, biomechanics, strength, and power. J Strength Cond Res 37(1): 181-186, 2023-The purpose of this study was to determine the differences between road (ROAD) vs. trail (TRAIL) elite runners in terms of force-velocity profile (FVP), running biomechanics, lower-limb maximal isometric strength, cost of running (Cr), and training. Seventeen male elite athletes (10 TRAIL and 7 ROAD) participated in this study. Force-velocity profile was measured using a 2-sprint test on a cycle ergometer. Strength was assessed with a dynamometer measuring isometric maximum voluntary torque of the knee extensors and knee flexors. Biomechanics parameters (running kinematics and stiffness) were measured, and Cr was calculated at 10 and 14 km·h-1 at 0% slope and at 10 km·h-1 on a 10% slope on a treadmill. Athletes also reported their training duration during the previous year. Theoretical maximal torque (F0) and maximal power (Pmax) in the FVP were higher for TRAIL vs. ROAD (122 ± 13 vs. 99 ± 7 N·m, p = 0.001; and 726 ± 89 vs. 626 ± 44 W; p = 0.016). Cost of running was higher for TRAIL compared with ROAD on flat at 14 km·h-1 (4.32 ± 0.22 vs. 4.06 ± 0.29 J·kg-1·m-1; p = 0.047) but similar at 10 km·h-1 and uphill. No differences were found in maximal isometric strength or running biomechanics. ROAD spent 81% more time training than TRAIL (p = 0.0003). The specific training (i.e., "natural" resistance training) performed during graded running in trail runners and training on level surface at high speed may explain our results. Alternatively, it is possible that trail running selects stronger athletes because of the greater strength requirements of graded running.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Acute effects of quadriceps muscle versus tendon prolonged local vibration on force production capacities and central nervous system excitability.

PURPOSE: The present study aimed to directly compare the effects of 30 min muscle (VIBmuscle) vs. tendon (VIBtendon) local vibration (LV) to the quadriceps on maximal voluntary isometric contraction (MVIC) and rate of torque development (RTD) as well as on central nervous system excitability (i.e. motoneuron and cortical excitability). METHODS: Before (PRE) and immediately after (POST) LV applied to the quadriceps muscle or its tendon, we investigated MVIC and RTD (STUDY #1; n = 20) or vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) electromyography responses to thoracic electrical stimulation (TMEPs; motoneuron excitability) and transcranial magnetic stimulation (MEPs; corticospinal excitability) (STUDY #2; n = 17). MEP/TMEP ratios were further calculated to quantify changes in cortical excitability. RESULTS: MVIC decreased at POST (P = 0.017) without any difference between VIBtendon and VIBmuscle, while RTD decreased for VIBtendon (P = 0.013) but not VIBmuscle. TMEP amplitudes were significantly decreased for all muscles (P = 0.014, P < 0.001 and P = 0.004 for VL, VM and RF, respectively) for both LV sites. While no changes were observed for MEP amplitude, MEP/TMEP ratios increased at POST for VM and RF muscles (P = 0.009 and P = 0.013, respectively) for both VIBtendon and VIBmuscle. CONCLUSION: The present results suggest that prolonged muscle and tendon LV are similarly effective in modulating central nervous system excitability and decreasing maximal force. Yet, altered explosive performance after tendon but not muscle LV suggests greater neural alterations when tendons are vibrated.

Fatigue Measured in Dynamic Versus Isometric Modes After Trail Running Races of Various Distances.

PURPOSE: Fatigue has previously been investigated in trail running by comparing maximal isometric force before and after the race. Isometric contractions may not entirely reflect fatigue-induced changes, and therefore dynamic evaluation is warranted. The aim of the present study was to compare the magnitude of the decrement of maximal isometric force versus maximal power, force, and velocity after trail running races ranging from 40 to 170 km. METHODS: Nineteen trail runners completed races shorter than 60 km, and 21 runners completed races longer than 100 km. Isometric maximal voluntary contractions (IMVCs) of knee extensors and plantar flexors and maximal 7-second sprints on a cycle ergometer were performed before and after the event. RESULTS: Maximal power output (Pmax; -14% [11%], P < .001), theoretical maximum force (F0; -11% [14%], P < .001), and theoretical maximum velocity (-3% [8%], P = .037) decreased significantly after both races. All dynamic parameters but theoretical maximum velocity decreased more after races longer than 100 km than races shorter than 60 km (P < .05). Although the changes in IMVCs were significantly correlated (P < .05) with the changes in F0 and Pmax, reductions in IMVCs for knee extensors (-29% [16%], P < .001) and plantar flexors (-26% [13%], P < .001) were larger (P < .001) than the reduction in Pmax and F0. CONCLUSIONS: After a trail running race, reductions in isometric versus dynamic forces were correlated, yet they are not interchangeable because the losses in isometric force were 2 to 3 times greater than the reductions in Pmax and F0. This study also shows that the effect of race distance on fatigue measured in isometric mode is true when measured in dynamic mode.

Bedside voluntary and evoked forces evaluation in intensive care unit patients: a narrative review.

Around one third of intensive care unit (ICU) patients will develop severe neuromuscular alterations, known as intensive care unit-acquired weakness (ICUAW), during their stay. The diagnosis of ICUAW is difficult and often delayed as a result of sedation or delirium. Indeed, the clinical evaluation of both Medical Research Council score and maximal voluntary force (e.g., using handgrip and/or handheld dynamometers), two independent predictors of mortality, can be performed only in awake and cooperative patients. Transcutaneous electrical/magnetic stimulation applied over motor nerves combined with the development of dedicated ergometer have recently been introduced in ICU patients in order to propose an early and non-invasive measurement of evoked force. The aim of this narrative review is to summarize the different tools allowing bedside force evaluation in ICU patients and the related experimental protocols. We suggest that non-invasive electrical and/or magnetic evoked force measurements could be a relevant strategy to characterize muscle weakness in the early phase of ICU and diagnose ICUAW.

Task failure during sustained low-intensity contraction is not associated with a critical amount of central fatigue.

Fatigue-related mechanisms induced by low-intensity prolonged contraction in lower limb muscles are currently unknown. This study investigated central fatigue kinetics in the knee extensors during a low-intensity sustained isometric contraction. Eleven subjects sustained a 10% maximal voluntary contraction (MVC) until task failure (TF) with neuromuscular evaluation every 3 minutes. Testing encompassed transcranial magnetic stimulation to evaluate maximal voluntary activation (VATMS ), motor evoked potential (MEP), and silent period (SP), and peripheral nerve stimulation to assess M-wave. Rating of perceived exertion (RPE) was also recorded. MVC progressively decreased up to 50% of the time to TF (ie, 50%TTF ) and then plateaued, reaching ~50% at TF (P < .001). VATMS progressively decreased up to 90%TTF and then plateaued, the decrease reaching ~20% at TF (P < .001). SP was lengthened early (ie, from 20%TTF ) during the exercise and then plateaued (P < .01). No changes were reported for MEP evoked during MVC (P = .87), while MEP evoked during submaximal contractions decreased early (ie, from 20%TTF ) during the exercise and then plateaued (P < .01). RPE increased linearly during the exercise to be almost maximal at TF. M-waves were not altered (P = .88). These findings confirm that TF is due to the subjects reaching their maximal perceived effort rather than any particular central event or neuromuscular limitations since MVC at TF was far from 10% of its original value. It is suggested that strategies minimizing RPE (eg, motivational self-talk) should be employed to enhance endurance performance.