Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome.

Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play a pivotal role. Thus, we aimed to measure the muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and assess mitochondrial morphology in CFS and PCS patients in comparison to healthy controls (HCs). Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers using high-resolution respirometry. Mitochondrial morphology (subsarcolemmal/intermyofibrillar mitochondrial form/cristae/diameter/circumference/area) and content (number and proportion/cell) were assessed via electron microscopy. Analyses included differences in OXPHOS between HC, CFS, and PCS, whereas comparisons in morphology/content were made for CFS vs. PCS. OXPHOS capacity of complex I, which was reduced in PCS compared to HC. While the subsarcolemmal area, volume/cell, diameter, and perimeter were higher in PCS vs. CFS, no difference was observed for these variables in intermyofibrillar mitochondria. Both the intermyofibrillar and subsarcolemmal cristae integrity was higher in PCS compared to CFS. Both CFS and PCS exhibit increased fatigue and impaired mitochondrial function, but the progressed pathological morphological changes in CFS suggest structural changes due to prolonged inactivity or unknown molecular causes. Instead, the significantly lower complex I activity in PCS suggests probably direct virus-induced alterations.

Longitudinal course of endocannabinoids and N-acylethanolamines in hair of mothers and their children in the first year postpartum: investigating the relevance of maternal childhood maltreatment experiences.

BACKGROUND: Childhood maltreatment (CM) exerts long-lasting psychological and biological alterations in affected individuals and might also affect the endocannabinoid (eCB) system which modulates inflammation and the endocrine stress response. Here, we investigated the eCB system of women with and without CM and their infants using hair samples representing eCB levels accumulated during the last trimester of pregnancy and 10-12 months postpartum. METHODS: CM exposure was assessed with the Childhood Trauma Questionnaire. At both timepoints, 3 cm hair strands were collected from mothers and children (N = 170 resp. 150) to measure anandamide (AEA), 2/1-arachidonoylglycerol (2-AG/1-AG), stearoylethanolamide (SEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA). RESULTS: Maternal hair levels of 2-AG/1-AG increased and SEA levels decreased from late pregnancy to one year postpartum. Maternal CM was associated with lower SEA levels in late pregnancy, but not one year later. In the children's hair, levels of 2-AG/1-AG increased while levels of SEA, OEA, and PEA decreased from late pregnancy to one year later. Maternal CM was not consistently associated with the eCB levels measured in children's hair. CONCLUSIONS: We provide first evidence for longitudinal change in the eCB system of mothers and infants from pregnancy to one year later. While maternal CM influenced the maternal eCB system, we found no consistent intergenerational effects on early regulation of the eCB system in children. Longitudinal research on the importance of the eCB system for the course and immunoregulation of pregnancy as well as for the children's development.

SARS-CoV-2 Altered Hemorheological and Hematological Parameters during One-Month Observation Period in Critically Ill COVID-19 Patients.

Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0-T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients.

Relationship Between Objective and Subjective Markers of Muscle Recovery in Professional Handball Players.

PURPOSE: To evaluate the relationship between items of the Short Recovery and Stress Scale (SRSS) related to physical stress and recovery and the biomarker creatine kinase (CK) in professional handball. METHODS: CK and SRSS items (physical performance capability, overall recovery, muscular stress, and overall stress) were assessed in an observational study of 16 adult male professional handball players from a team in the highest German league during the 2019-20 preseason. Their preseason training schedule included several microcycles, each consisting of 3 consecutive days of intense training followed by a rest day. On 5 of these rest days, when players were classified as nonrested, and the 5 immediately following days, when players were classified as rested, players completed the SRSS between 8:00 and 9:00 AM, followed by blood sampling. Correlations between SRSS items were performed using Kendall τ. The relationship between each SRSS item and CK levels over time was examined using a mixed-effects model with a random intercept. RESULTS: CK levels and SRSS stress items were significantly higher and SRSS recovery items were significantly lower in nonrested players. SRSS items were significantly positively or negatively correlated (all items: P < .001) and showed a significant effect indicating lower CK levels in rested players (all items: P ≤ .001; ηp2=.1-.32). CONCLUSIONS: The investigated SRSS items may be a viable option for assessing muscle recovery in adult male professional handball players in a cost-effective and noninvasive manner. They can be used as a single monitoring tool or as part of a multimodal approach.

The Influence of a Polyphenol-Rich Red Berry Fruit Juice on Recovery Process and Leg Strength Capacity after Six Days of Intensive Endurance Exercise in Recreational Endurance Athletes.

BACKGROUND: Various nutritional strategies are increasingly used in sports to reduce oxidative stress and promote recovery. Chokeberry is rich in polyphenols and can reduce oxidative stress. Consequently, chokeberry juices and mixed juices with chokeberry content are increasingly used in sports. However, the data are very limited. Therefore, this study investigates the effects of the short-term supplementation of a red fruit juice drink with chokeberry content or a placebo on muscle damage, oxidative status, and leg strength during a six-day intense endurance protocol. METHODS: Eighteen recreational endurance athletes participated in a cross-over high intensity interval training (HIIT) design, receiving either juice or a placebo. Baseline and post-exercise assessments included blood samples, anthropometric data, and leg strength measurements. RESULTS: A significant increase was measured in muscle damage following the endurance protocol in all participants (∆ CK juice: 117.12 ± 191.75 U/L, ∆ CK placebo: 164.35 ± 267.00 U/L; p = 0.001, η2 = 0.17). No group effects were detected in exercise-induced muscle damage (p = 0.371, η2 = 0.010) and oxidative status (p = 0.632, η2 = 0.000). The reduction in strength was stronger in the placebo group, but group effects are missing statistical significance (∆ e1RM juice: 1.34 ± 9.26 kg, ∆ e1RM placebo: -3.33 ± 11.49 kg; p = 0.988, η2 = 0.000). CONCLUSION: Although a reduction in strength can be interpreted for the placebo treatment, no statistically significant influence of chokeberry could be determined. It appears that potential effects may only occur with prolonged application and a higher content of polyphenols, but further research is needed to confirm this.

Decreased physical performance despite objective and subjective maximal exhaustion in post-COVID-19 individuals with fatigue.

INTRODUCTION: Fatigue is a common symptom in post-COVID-19 patients. Individuals with fatigue often perform less well compared to healthy peers or without fatigue. It is not yet clear to what extent fatigue is related to the inability to reach maximum exhaustion during physical exercise. METHODS: A symptom-based questionnaire based on the Carruthers guidelines (2003) was used for reporting the presence of fatigue and further symptoms related to COVID-19 from 85 participants (60.0% male, 33.5 ± 11.9 years). Cardiopulmonary exercise testing (CPET) and lactate measurement at the end of the test were conducted. Objective and subjective exhaustion criteria according to Wasserman of physically active individuals with fatigue (FS) were compared to those without fatigue (NFS). RESULTS: Differences between FS and NFS were found in Peak V̇O2/BM (p < 0.001) and Max Power/BM (p < 0.001). FS were more likely to suffer from further persistent symptoms (p < 0.05). The exhaustion criterion Max. lactate was reached significantly more often by NFS individuals. CONCLUSION: Although the aerobic performance (Max Power/BM) and the metabolic rate (Peak V̇O2/BM and Max. lactate) of FS were lower compared to NFS, they were equally able to reach objective exhaustion criteria. The decreased number of FS who reached the lactate criteria and the decreased V̇O2 peak indicates a change in metabolism. Other persistent post-COVID-19 symptoms besides fatigue may also impair performance, trainability and the ability to reach objective exhaustion. Trial registration Trial registration: DRKS00023717; date of registration: 15.06.2021 (retrospectively registered).

Blood Profiling of Athletes after COVID-19: Differences in Blood Profiles of Post-COVID-19 Athletes Compared to Uninfected Athletic Individuals-An Exploratory Analysis.

Blood profiling data in athletic populations and their respective responses to SARS-CoV-2 infection are lacking. Thus, this exploratory pilot study aimed to analyze and compare clinical blood markers in previously infected trained athletes (ATH; 30 m/29 f) and a not previously infected healthy athletic control group (HC; 12 m/19 f). The ATH group undertook a sports medical examination which included extended blood analyses. Blood profiles with a total of 74 variables were assessed (blood counts, pro-/inflammatory and immunological markers, and micronutrients), and the ATH group was compared to the age-matched, vaccinated HC group with comparable athletic back grounds, though without previous SARS-CoV-2-infections. The ATH group showed lower IgG, Troponin-T levels, and they had a lower complement/acute-phase protein activation. Furthermore, Vitamin D levels were lower and electrolyte/micronutrient concentrations were higher in ATH. Soluble transferrin receptor as a marker of erythrocyte turnover was decreased whereas PTT as a coagulation marker was increased. Subgroup analyses according to sex revealed more differences between the women of the ATH and HC groups (for 25 different variables) than between the men (for 5 different variables), especially for immunological and metabolic variables. In particular, the immune system and electrolyte/micronutrient status should be observed frequently and sex-specifically in this athletic cohort.

Left Ventricular Global Longitudinal Strain as a Parameter of Mild Myocardial Dysfunction in Athletes after COVID-19.

Whether symptoms during COVID-19 contribute to impaired left ventricular (LV) function remains unclear. We determine LV global longitudinal strain (GLS) between athletes with a positive COVID-19 test (PCAt) and healthy control athletes (CON) and relate it to symptoms during COVID-19. GLS is determined in four-, two-, and three-chamber views and assessed offline by a blinded investigator in 88 PCAt (35% women) (training at least three times per week/>20 MET) and 52 CONs from the national or state squad (38% women) at a median of two months after COVID-19. The results show that the GLS is significantly lower (GLS -18.53 ± 1.94% vs. -19.94 ± 1.42%, p < 0.001) and diastolic function significantly reduces (E/A 1.54 ± 0.52 vs. 1.66 ± 0.43, p = 0.020; E/E'l 5.74 ± 1.74 vs. 5.22 ± 1.36, p = 0.024) in PCAt. There is no association between GLS and symptoms like resting or exertional dyspnea, palpitations, chest pain or increased resting heart rate. However, there is a trend toward a lower GLS in PCAt with subjectively perceived performance limitation (p =0.054). A significantly lower GLS and diastolic function in PCAt compared with healthy peers may indicate mild myocardial dysfunction after COVID-19. However, the changes are within the normal range, so that clinical relevance is questionable. Further studies on the effect of lower GLS on performance parameters are necessary.

Randomized controlled trial investigating potential effects of relaxation on mitochondrial function in immune cells: A pilot experiment.

This study aimed to investigate the effect of a relaxation response induced by hypnosis on the mitochondrial energy production of immune cells compared to an everyday relaxing situation. Chronically stressed individuals (88% women) with at least moderate suggestibility were randomized to a hypnosis (20 min relaxation hypnosis; n = 20) or a control condition (20 min documentary; n = 22). Before and after intervention, peripheral blood was collected. The primary outcomes were mitochondrial respiration and density in immune cells measured by high-resolution respirometry and citrate synthase activity assays. As secondary outcome, perceived stress, anxiety, and depressive mood were assessed. The intervention led to no significant Group × Time effects on mitochondrial bioenergetic parameters but a significant Time effect (ηp2 = .09 -.10). Thus, there were no differences in the experimental conditions concerning the measured parameters of mitochondrial bioenergetics. Exploratory subanalyses indicated that stress, anxiety, and depressive mood were linked to lower mitochondrial respiration. Individuals with higher anxiety had less decrease in routine respiration over time than those with lower anxiety (ηp2 = .09). This study explores the effects of relaxation in the form of hypnosis compared to watching a video on the energy metabolism of immune cells. Relaxation, whether in targeted (hypnosis) or untargeted (documentary) form, affected mitochondrial respiration. Further research should focus on the long-term effects of relaxation on bioenergetics. The trial was retrospectively registered on 07/12/2021, DRKS00027356, https://drks.de/search/de/trial/DRKS00027356.

Relationship between physical performance and perception of stress and recovery in daily life post COVID-19-An explorative study.

INTRODUCTION: COVID-19 is a multi-systemic disease which can target the lungs and the cardiovascular system and can also affect parts of the brain for prolonged periods of time. Even healthy athletes without comorbidities can be psychologically affected long-term by COVID-19. OBJECTIVE: This study aimed to investigate athletes' perceived mental stress and recovery levels in daily life, and their maximal aerobic power, at three different time points, post COVID-19. METHODS: In total, 99 athletes (62.6% male), who had been infected by COVID-19, filled out the Recovery Stress Questionnaire for Athletes (REST-Q-Sport) and completed cardiopulmonary exercise testing (endpoint maximal aerobic power output (Pmax)) at the initial screening (t1: 4 months after infection). Follow-up assessments occurred three (t2, n = 37) and seven months after t1 (t3, n = 19). RESULTS: Subgroup means from the Recovery category were significantly below the reference value of four at all three time points, except "General Recovery" (3.76 (± 0.96), p = 0.275, d = 0.968) at t3."Overtiredness" (2.34 (± 1.27), p = 0.020, r = 0.224) was significantly above the reference value of two at t1, while all other Stress subgroups were not significantly different from the reference value or were significantly below the maximum threshold of two at t1, t2 and t3. Spearman's ρ revealed a negative association between Pmax and the subcategories of stress (ρ = -0.54 to ρ = -0.11, p < 0.050), and positive correlations between Pmax and "Somatic Recovery" (ρ = 0.43, p < 0.001) and "General Recovery" (ρ = 0.23, p = 0.040) at t1. Pmax (t1: 3.83 (± 0.99), t2: 3.78 (± 1.14), ß = 0.06, p < 0.003) increased significantly from t1 to t2. In addition, REST-Q-Sport indicated a decrease in "Sleep" (t2 = 2.35 (± 0.62), t3 = 2.28(± 0.61), ß = -0.18, p < 0.023) at t3, when compared to t2. CONCLUSION: The perceived recovery seems to be negatively affected in post COVID-19 athletes. Physical performance post COVID-19 correlates with both "Emotional and Somatic Stress" and "Somatic and General Recovery", indicating potential mental and physical benefits of exercise. While it is evident that COVID-19, like other viral infections, may have an influence on physical performance, monitoring stress and recovery perceptions of athletes is critical to facilitate their return-to-sports, while minimizing long-term COVID-19 induced negative effects like the athletic objective and subjective perceived recovery and stress levels.

An exploratory study of hypnosis-induced blood count changes in chronically stressed individuals.

Hypnosis is a clinically accepted relaxation technique known for stress reduction. Results from hematological research provide evidence of changes in blood components through hypnosis. However, these hematological effects have been rarely examined. Hence, we exploratively investigated the effect of a single relaxation hypnosis on the hemogram in stressed individuals, assuming a reduction of leukocytes, thrombocytes, and erythrocytes (primary outcomes). Additionally, a reduction in the erythrocyte-related parameters (hemoglobin, hematocrit), and an increase in plasma volume was hypothesized (secondary outcomes). Forty-four either individuals (89 % women) with chronic stress and moderate to high hypnotic suggestibility were randomized to a hypnosis condition (20 min relaxation hypnosis; n = 20) or a control condition (20 min documentary; n = 24). Venous blood was drawn before and after the intervention and used to generate a differential hemogram and determine the plasma volume. The relaxation hypnosis led to a significant reduction in erythrocytes (Cohen's d=0.23) and consequently to a decrease in erythrocyte-related parameters (hemoglobin, d=0.27; hematocrit, d=0.37) as well as to a reduction in thrombocytes (d=0.15) in the hypnosis compared to the control condition. Putatively, this could be the consequence of an increased plasma volume (d=0.10), estimated by the hematocrit concentration and body weight. A hypnosis-induced change in leukocyte count could not be confirmed. Thus, a single session of relaxation hypnosis already alters specific blood count parameters. While relaxation-induced vasodilatation might explain these changes, it is still not completely clear how these changes affect our stress response system.

Inflammation and severity of depressive symptoms in physically active individuals after COVID-19 - An exploratory immunopsychological study investigating the effect of inflammation on depressive symptom severity.

Background: SARS-CoV-2 infection is a risk factor for the development of depressive symptoms such as lack of energy, loss of interest, and depressed mood. Inflammatory processes might underline this association. The aim of this study was to investigate the association between inflammatory markers and the severity of depression after SARS-CoV-2 infection and the predictive effect of inflammatory markers on the severity of depressive symptoms. Lifestyle factors and lifestyle-related diseases can influence inflammation and depressive symptoms. As these lifestyle factors and lifestyle-related diseases are less common in physically active individuals, they are a suitable population for investigating this research question. Methods: We investigated 61 at least moderate physically active individuals on average ∼6 months (SD = 4.22, range = 0.5-19 months) after SARS-CoV-2 infection (t0) and performed a follow-up after 3 months (t1). Depressive symptoms and biomarkers of inflammation (interleukin [IL]-1ß, IL-8, IL-10, Ferritin, Lipopolysaccharide-binding-protein [LBP], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR]) and kynurenine [KYN] were measured at both time points. Concentrations of inflammatory markers at t0 were used to predict the severity of depressive symptoms at t0 and t1. Results: Concentrations of KYN were negatively related to the severity of depressive symptoms at t0. Concentrations of LMR predicted higher depressive symptoms at t0 as well as at t1. Furthermore, individuals with lower concentrations of LBP at t0 showed a higher severity of depressive symptoms at t1. No correlation was found between severity of depressive symptoms and IL-1ß, IL-8, IL-10, ferritin, NLR, and PLR at both time points. Conclusions: KYN, LBP and LMR might be useful as a predictive factor of depressive symptoms in physically active individuals after SARS-CoV-2 infection. While the results for KYN confirm the current scientific evidence, our results highlight the importance of the innovative inflammatory markers LMR and LBP. LMR and LBP might be interesting targets for predicting the development of depressive symptoms in SARS-CoV-2 infected populations and should be further investigated in future studies.

Recovery of performance and persistent symptoms in athletes after COVID-19.

INTRODUCTION: After the acute Sars-CoV-2-infection, some athletes suffer from persistent, performance-impairing symptoms, although the course of the disease is often mild to moderate. The relation between cardiopulmonary performance and persistent symptoms after the acute period is still unclear. In addition, information about the development of this relationship is lacking. OBJECTIVE: To assess the prevalence of persistent symptoms over time and their association with the performance capability of athletes. METHODS: We conducted two cardiopulmonary exercise tests (CPET) in a three months interval with 60 athletes (age: 35.2±12.1 years, 56.7% male) after infection with Sars-CoV-2 (t0: study inclusion; t1: three months post t0). At each examination, athletes were asked about their persistent symptoms. To evaluate the change of Peak VO2/BM (Body Mass) between the time before infection and the first examination, the VO2/BM (predVO2) before infection was predicted based on anthropometric data and exercise history of the athletes. For data analysis, athletes were grouped according to their symptom status (symptom-free, SF; persistent symptoms, PS) and its progression from the first to the second examination 1) SF-SF, 2) PS-SF and 3) PS-PS. RESULTS: Comparing the SF and PS groups at t0, significant differences for Max Power/BM, Max Power/lbm (lean body mass), Peak VO2, Peak VO2/BM, Peak VO2/lbm, Peak VO2/HR, Peak VE, Peak Vt and VE/VCO2-Slope were observed. Regarding the progression over three months, an increase in Max Power/BM was shown in SF-SF and PS-SF (tendency). Max Power/lbm increased in SF-SF and PS-PS (tendency). A decrease of VE/VCO2-Slope in PS-PS was found. CONCLUSION: COVID-19 led to a decline in performance that was greater in PS than in SF. Additionally, PS had decreased ventilatory parameters compared to SF. Furthermore, an improvement over time was observed in some CPET parameters and a partial recovery was observed judging by the decrease in various symptoms.

Atypical maternal interaction is associated with elevated levels of hair cortisol in children.

The quality of maternal caregiving is an important factor in the healthy development of a child. One consequence of prolonged insensitive and atypical maternal interaction behavior (e.g., withdrawing from interactions with the child and role-reversal, i.e., the takeover of the parental role or parts of it by the child) in mother-child-dyads can cause alteration of the child's stress response system. Higher salivary cortisol concentrations were reported in infants and toddlers directly after negative interactions with their parents. However, no study to date has examined the association between atypical maternal interaction behavior and hair cortisol concentrations (HCC) in infants. Here, we studied the association of maternal interaction behavior with HCC of the child. Mother-child dyads (N = 112) participated in the longitudinal study My Childhood-Your Childhood. The AMBIANCE scale and its subscales were used to assess atypical maternal interaction behavior during the Strange Situation Procedure. Chronic stress levels in the child were assessed by HCC of 3 cm hair strands at the age of 12 months. Maternal educational level (operationalized in highest education level) served as a control variable. Robust multiple linear regression analyses revealed that role/boundary confusion was associated with HCC, i.e., the higher atypical interaction behavior of the mother the higher the HCC in the children. By measuring hair cortisol in this study, it is possible to determine the average long-term activity of the child's stress response system.Thus, atypical maternal interaction behavior could be a risk factor for persistent stress in children, contributing to a higher risk for negative health outcomes in later life. The results of this study highlight the importance of early intervention programs that focus on the relationship between mother and child.

Therapists' Experiences With the Effectiveness and Feasibility of Videoconference-Based Eye Movement Desensitization and Reprocessing.

Research on the effectiveness and applicability of eye movement desensitization and reprocessing (EMDR) via videoconference is sparse. Considering the emerging use of internet-based psychotherapy during the COVID-19 pandemic, information on videoconference-based EMDR (eEMDR) would be beneficial for many therapists. In this study, 23 therapists from the EMDR-Institute in Germany provided information about their experiences with eEMDR in a questionnaire-based survey. Information on the effectiveness and the course of 102 eEMDR sessions was recorded. Results showed the potential of eEMDR as an effective and viable method. The decrease in the subjective unit of disturbance (SUD), which is an important indicator of treatment outcome, was found to be at a similar level compared to that of previous EMDR studies that were not administered in eEMDR format. The most important predictor of the SUD decrease was the type of bilateral stimulation used in eEMDR sessions. Eye movements resulted in significantly greater SUD reductions than tapping. Perceived disadvantages and impediments for the implementation of eEMDR were mainly of bureaucratic and technical concerns. In addition, about one-third of the therapists stated that some patients were not willing to engage in eEMDR. In our study, eEMDR proved to be a practically applicable therapy method and therefore, therapists can consider using eEMDR. These findings will hopefully encourage EMDR therapists and their patients to use eEMDR due to its effectiveness and viability as an online treatment approach.