Remote Exercise Training Intervention During the COVID-19 Pandemic: Randomized Controlled Trial.

BACKGROUND: Societal measures to contain the spread of COVID-19 (eg, lockdown and contact restrictions) have been associated with decreased health and well-being. A multitude of prepandemic studies identified the beneficial effects of physical exercise on both physical and mental health. OBJECTIVE: We report on the feasibility of a remote physical exercise intervention and its stress-buffering potential in 2 untrained cohorts: a pre-COVID-19 cohort that completed the intervention in 2019 and a lockdown cohort that started the intervention shortly before pandemic-related restrictions were implemented. METHODS: In a randomized controlled trial, participants were assigned to either an intervention group (IG; pre-COVID-19 cohort: n=7 and lockdown cohort: n=9) or a control group (CG; pre-COVID-19 cohort: n=6 and lockdown cohort: n=6). IG participants received weekly individualized training recommendations delivered via web-based support. The intervention period was initially planned for 8 weeks, which was adhered to in the pre-COVID-19 cohort (mean 8.3, SD 0.5 weeks) but was extended to an average of 17.7 (SD 2.0) weeks in the lockdown cohort. Participants' health parameters were assessed before and after the intervention: aerobic capacity was measured as peak oxygen uptake (VO2peak) via cardiopulmonary exercise testing. Depressive symptoms were scored via the depression subscale of the Brief Symptom Inventory-18. RESULTS: Dropout rates were low in both cohorts in the IG (pre-COVID-19 cohort: n=0, 0% and lockdown cohort: n=2, 16.7%) and the CG (pre-COVID-19 cohort: n=0, 0% and lockdown cohort: n=2, 20%). The mean adherence to the training sessions of the IG for both cohorts was 84% (pre-COVID-19 cohort: SD 5.5% and lockdown cohort: SD 11.6%). Aligned rank transform ANOVAs in the lockdown cohort indicated deterioration of VO2peak and depressive symptoms from before to after the intervention in the CG but no longitudinal changes in the IG. Analyses in the pre-COVID-19 cohort revealed significant increases in VO2peak for the IG compared to the CG (P=.04) but no intervention effects on depressive symptoms. CONCLUSIONS: With low dropout rates and high adherence, the remote intervention was feasible for healthy adults under regular conditions and in the face of pandemic-related stressors. Moreover, our results hint at a stress-buffering effect as well as a buffering of a lockdown-induced deconditioning of remote physical exercise interventions in the pandemic scenario, which can be used in future studies to overcome equally stressful periods of life. However, due to limited statistical power, these findings should be replicated in similar scenarios. TRIAL REGISTRATION: German Clinical Trials Register DRKS00018078; https://drks.de/search/en/trial/DRKS00018078.

Physical activity specifically evokes release of cell-free DNA from granulocytes thereby affecting liquid biopsy.

Physical activity impacts immune homeostasis and leads to rapid and marked increase in cell-free DNA (cfDNA). However, the origin of cfDNA during exercise remains elusive and it is unknown if physical activity could improve or interfere with methylation based liquid biopsy. We analyzed the methylation levels of four validated CpGs representing cfDNA from granulocytes, lymphocytes, monocytes, and non-hematopoietic cells, in healthy individuals in response to exercise, and in patients with hematological malignancies under resting conditions. The analysis revealed that physical activity almost exclusively triggered DNA release from granulocytes, highlighting the relevance as a pre-analytical variable which could compromise diagnostic accuracy.

Validating quantitative PCR assays for cfDNA detection without DNA extraction in exercising SLE patients.

Circulating cell-free DNA (cfDNA) has been investigated as a screening tool for many diseases. To avoid expensive and time-consuming DNA isolation, direct quantification PCR assays can be established. However, rigorous validation is required to provide reliable data in the clinical and non-clinical context. Considering the International Organization for Standardization, as well as bioanalytical method validation guidelines, we provide a comprehensive procedure to validate assays for cfDNA quantification from blood plasma without DNA isolation. A 90 and 222 bp assay was validated to study the kinetics of cfDNA after exercise in patients with systemic lupus erythematosus (SLE). The assays showed ultra-low limit of quantification (LOQ) with 0.47 and 0.69 ng/ml, repeatability ≤ 11.6% (95% CI 8.1-20.3), and intermediate precision ≤ 12.1% (95% CI 9.2-17.7). Incurred sample reanalysis confirmed the precision of the procedure. The additional consideration of pre-analytical factors shows that centrifugation speed and temperature do not change cfDNA concentrations. In SLE patients cfDNA increases ~ twofold after a walking exercise, normalizing after 60 min of rest. The established assays allow reliable and cost-efficient quantification of cfDNA in minute amounts of plasma in the clinical setting. Additionally, the assay can be used as a tool to determine the impact of pre-analytical factors and validate cfDNA quantity and quality of isolated samples.

Association of Innate and Acquired Aerobic Capacity With Resilience in Healthy Adults: Protocol for a Randomized Controlled Trial of an 8-Week Web-Based Physical Exercise Intervention.

BACKGROUND: Physical activity alleviates chronic stress. The latest research suggests a relationship between resilience and physical fitness. Beneficial adaptations of the hypothalamic-pituitary-adrenal axis, sympathetic nervous system, endocannabinoid system, and tryptophan pathway, which are induced by an active lifestyle, are considered to be conducive to resilience. However, detailed knowledge on the molecular link between the effects of acute and chronic physical exercise and improved resilience to stress in humans is missing. Moreover, the relationship between innate and acquired aerobic capacity and resilience is poorly understood. OBJECTIVE: The aim of this study is to implement a human exercise intervention trial addressing the following main hypotheses: a high innate aerobic capacity is associated with high resilience to stress, and web-based physical exercise training improves aerobic capacity of physically inactive adults, which is accompanied by improved resilience. In this setting, we will analyze the relationship between resilience parameters and innate and acquired aerobic capacity as well as circulating signaling molecules. METHODS: A total of 70 healthy, physically inactive (<150 minutes/week of physical activity) adults (aged 18-45 years) will be randomly assigned to an intervention or control group. Participants in the intervention group will receive weekly training using progressive endurance and interval running adapted individually to their remotely supervised home training performance via web-based coach support. A standardized incremental treadmill exercise test will be performed before and after the intervention period of 8 weeks to determine the innate and acquired aerobic capacity (peak oxygen uptake). Before and after the intervention, psychological tests and questionnaires that characterize parameters implicated in resilience will be applied. Blood and saliva will be sampled for the analysis of cortisol, lactate, endocannabinoids, catecholamines, kynurenic acid, and further circulating signal transducers. Statistical analysis will provide comprehensive knowledge on the relationship between aerobic capacity and resilience, as well as the capacity of peripheral factors to mediate the promoting effects of exercise on resilience. RESULTS: The study was registered in October 2019, and enrollment began in September 2019. Of the 161 participants who were initially screened via a telephone survey, 43 (26.7%) fulfilled the inclusion criteria and were included in the study. Among the 55% (17/31) of participants in the intervention group and 45% (14/31) of participants in the control group who completed the study, no serious adverse incidents were reported. Of 43 participants, 4 (9%) withdrew during the program (for individual reasons) and 8 (19%) have not yet participated in the program; moreover, further study recruitment was paused for an indeterminate amount of time because of the COVID-19 pandemic. CONCLUSIONS: Our study aims to further define the physiological characteristics of human resilience, and it may offer novel approaches for the prevention and therapy of mental disorders via an exercise prescription. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29712.