BUSCADOR RECOLECTA

Background: physical exercise induces a coordinated response of multiple organ systems, including the immune
system. In fact, it has been proposed that physical exercise may modulate the immune system. However, the potential
effect of an exercise program on COVID-19 survivors has not been investigated. Thus, the aim of this study is to evaluate
the modifications in immunological parameters, physical condition, inflammatory profile, and perceived persistent
symptoms after 6 weeks of supervised resistance training (RT), in addition to the standard care on the clinical status
of patients with persistent COVID-19 symptoms. The objective of this protocol is to describe the scientific rationale in
detail and to provide information about the study procedures.
Methods/design: a total of 100 patients with postdischarge symptoms after COVID-19 will be randomly allocated
into either a group receiving standard care (control group) or a group performing a multicomponent exercise
program two times a week over a period of 6 weeks. The main hypothesis is that a 6-week multicomponent exercise
program (EXER-COVID Crossover Study) will improve the immunological and inflammatory profile, physical condition,
and persistent perceived symptoms (fatigue/tiredness, musculoskeletal pain, and shortness of breath) in patients with
postdischarge symptoms after COVID-19.
Discussion: our results will provide insights into the effects of a multicomponent exercise program on immunological
parameters, physical condition, inflammatory profile, and persistent perceived symptoms in patients with postdischarge
symptoms after COVID-19. Information obtained by this study will inform future guidelines on the exercise
training rehabilitation of patients with postdischarge symptoms after COVID-19., The EXER-COVID Crossover Study was supported by «Proyectos de I+D+i» de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RB-I00).

Esta tesis doctoral se basa en un ensayo clínico cruzado, realizado dentro del grupo E-FIT (Ejercicio Físico, Salud y Calidad de Vida) denominado 'Efectos de un programa de ejercicio físico multicomponente sobre el sistema inmune, el perfil inflamatorio, la condición física y los síntomas percibidos persistentes (fatiga/cansancio, dolor musculoesquelético, dificultad para respirar) en sobrevivientes a la enfermedad por coronavirus (COVID-19): Un ensayo clínico cruzado'.
Nuestra hipótesis de trabajo es que con la aplicación de un programa de ejercicio multicomponente de 6 semanas de duración podríamos reducir el grado de percepción de los síntomas percibidos persistentes (fatiga/cansancio, dolor musculoesquelético, dificultad para respirar), a través de la modulación del sistema endocannabinoide, mejoraríamos el perfil inmunológico a través de la modificación gradual del sistema inmune provocado ya sea por el avance natural de la edad o por la infección de la COVID-19, incrementaríamos la condición física (capacidad funcional, fitness aeróbico y fuerza muscular) por efecto de la acción mecánica y endocrina, y reduciríamos la producción de citoquinas inflamatorias derivadas de mononucleares de sangre periférica tales como IL-1 beta, IL-6 y TNF-alfa a través del aumento de la producción y liberación de citocinas antiinflamatorias debido a la contracción del músculo esquelético, lo cual podría contribuir a reducir el proceso inflamatorio que habitualmente se instaura en la infección por la COVID-19.
Los objetivos de este estudio fueron: evaluar la modificación en parámetros inmunológicos, condición física, perfil inflamatorio y cambios en síntomas percibidos persistentes (fatiga/cansancio, dolor musculoesquelético, dificultad para respirar) después de 6 semanas de ejercicio físico multicomponente y supervisado, adicionales al esquema de tratamiento médico estándar en pacientes con síntomas persistentes de la COVID-19.
Antecedentes: La condición post-COVID-19 es una condición novedosa para la cual las guías recomiendan ejercicio supervisado, pero la evidencia que guía intervenciones seguras y efectivas es limitada. El objetivo de este estudio fue investigar los efectos de un programa de ejercicio adaptado (ensayo EXER-COVID) sobre la aptitud cardiorrespiratoria, la fuerza muscular, los síntomas COVID prolongados, el rendimiento cognitivo, la calidad de vida, la depresión y la angustia psicológica.
Métodos: Este estudio cruzado incluyó 100 participantes con condiciones post-COVID-19 (edad media 48 años; 68% mujeres) en un único centro en España desde el 1 de marzo de 2021 hasta el 30 de septiembre de 2022. Los participantes fueron aleatorizados 1:1 a 6 semanas de entrenamiento de resistencia a la potencia muscular (PRT) seguido de 6 semanas de atención habitual (Grupo 1 [AB], n=50) o 6 semanas de atención habitual seguidas de 6 semanas de RT de potencia muscular (Grupo 2 [BA], n=50).
Resultados: La intervención mejoró significativamente el pico de VO2 en 2,10 ml/kg/min [IC 95%: 1,25 a 2,94], P<0,001. Los análisis por protocolo revelaron resultados similares (2,40 ml/kg/min [IC del 95%: 1,56 a 3,25]), P<0,001. No se detectaron efectos de arrastre ni de período. Después de la PRT de potencia, la fuerza (1RM) mejoró para la prensa pectoral, la prensa bilateral de piernas, la extensión de rodillas y la prensa de espalda (P<0,001). Se encontraron disminuciones significativas en las puntuaciones de angustia psicológica (P<0,001). La intervención también mejoró la calidad de vida (P=0,041), las capacidades cognitivas (P=0,014) y el rendimiento cognitivo (P=0,036). Además, el programa de ejercicios redujo siete de los 22 síntomas de la COVID prolongada, entre ellos debilidad (RR= 0,75 [IC 95%: 0,59 a 0,95]), disnea (RR= 0,56 [IC 95%: 0,39 a 0,82]), pérdida de audición/tinnitus (RR= 0,86 [IC 95%: 0. 75 a 0,98]), cambios en el apetito (RR= 0,84 [IC 95%: 0,72 a 0,97]), pérdida de memoria (RR= 0,84 [IC 95%: 0,72 a 0,97]), estrés (RR= 0,80 [IC 95%: 0,64 a 0,99]) y apatía/depresión (RR= 0,80 [IC 95%: 0,64 a 0,99]).
Conclusiones: Un programa de intervención PRT supervisado de 6 semanas mejoró de forma segura la aptitud cardiorrespiratoria, la fuerza y la salud mental en participantes con afecciones posteriores al COVID-19. Estos hallazgos proporcionan a los médicos pruebas para apoyar el ejercicio como co-terapia estándar y justifican estudios adicionales. Registro del ensayo: NCT04797871. Registrado el 15 de marzo de 2021., This Doctoral Thesis is based on a crossover clinical trial, conducted within the E-FIT (Physical Exercise, Health and Quality of Life) group entitled 'Effects of a multicomponent physical exercise programme on the immune system, inflammatory profile, physical fitness and persistent perceived symptoms (fatigue/tiredness, musculoskeletal pain, shortness of breath) in survivors of coronavirus disease (COVID-19): A crossover clinical trial'.
Our working hypothesis is that with the application of a 6-week multicomponent exercise programme we could reduce the degree of perception of persistent perceived symptoms (fatigue/tiredness, musculoskeletal pain, shortness of breath), through modulation of the endocannabinoid system, improve the immune profile through gradual modification of the immune system caused by either natural age progression or COVID-19 infection, increase physical fitness (functional capacity, aerobic fitness and muscular strength) through mechanical and endocrine action, and reduce the production of inflammatory cytokines derived from blood mononuclear peripheral vascular monocytes, increase physical fitness (functional capacity, aerobic fitness and muscle strength) through mechanical and endocrine action, and reduce the production of peripheral blood mononuclear derived inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha through increased production and release of anti-inflammatory cytokines due to skeletal muscle contraction, which could contribute to reducing the inflammatory process that typically occurs in COVID-19 infection.
The objectives of this study were: to evaluate the modification in immunological parameters, physical condition, inflammatory profile and changes in perceived persistent symptoms (fatigue/tiredness, musculoskeletal pain, shortness of breath) after 6 weeks of multicomponent and supervised physical exercise, in addition to the standard medical treatment scheme in patients with persistent symptoms of COVID-19.
Background: The post-COVID-19 condition is a novel condition for which guidelines recommend supervised exercise, but evidence guiding safe and effective interventions is limited. The aim of this study was to investigate the effects of a tailored exercise program (EXER-COVID trial) on cardiorespiratory fitness, muscle strength, long COVID symptoms, cognitive performance, quality of life, depression, and psychological distress.
Methods: This crossover study included 100 participants with post-COVID-19 conditions (mean age 48 years; 68% women) at a single center in Spain from March 1, 2021, to September 30, 2022. Participants were randomized 1:1 to 6 weeks of muscle power resistance training (PRT) followed by 6 weeks of usual care (Group 1 [AB], n=50) or 6 weeks of usual care followed by 6 weeks of muscle power RT (Group 2 [BA], n=50).
Results: The intervention significantly improved the peak VO2 by 2.10 mL/kg/min [95% CI 1.25 to 2.94], P<0.001. Per-protocol analyses revealed similar results (2.40 mL/kg/min [95% CI 1.56 to 3.25]), P<0.001. No carry-over or period effects were detected. After power PRT, strength (1RM) was improved for pectoral press, bilateral leg-press, knee extension, and back press (P<0.001). Significant decreases were found in psychological distress scores (P<0.001). The intervention also improved quality of life (P=0.041), cognitive capabilities (P=0.014) and cognitive performance (P=0.036). Furthermore, the exercise program reduced seven of the 22 long-COVID symptoms, including weakness (RR= 0.75 [95% CI 0.59 to 0.95]), dyspnea (RR= 0.56 [95% CI 0.39 to 0.82]), hearing loss/tinnitus (RR= 0.86 [95% CI 0.75 to 0.98]), change in appetite (RR= 0.84 [95% CI 0.72 to 0.97]), memory loss (RR= 0.84 [95% CI 0.72 to 0.97]), stress (RR= 0.80 [95% CI 0.64 to 0.99]) and apathy/depression (RR= 0.80 [95% CI 0.64 to 0.99]).
Conclusions: A supervised 6-week PRT intervention program safely improved cardiorespiratory fitness, strength, and mental health in participants with post-COVID-19 conditions. These findings provide clinicians with evidence to support exercise as standard co-therapy and warrant further study. Trial registration: NCT04797871. Registered March 15, 2021., Beca doctoral del Centro de Investigación Biomédica Navarrabiomed. Este proyecto ha sido subvencionado por 'Proyectos de I+D+I' de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RB-I00)., Programa de Doctorado en Ciencias de la Salud (RD 99/2011), Osasun Zientzietako Doktoretza Programa (ED 99/2011)

Exercise intolerance remains a major unmet medical need in patients with heart failure (HF). Skeletal myopathy
is currently considered as the major limiting factor for exercise capacity in HF patients. On the other hand,
emerging evidence suggest that physical exercise can decrease morbidity and mortality in HF patients. Therefore,
mechanistic insights into skeletal myopathy may uncover critical aspects for therapeutic interventions to
improve exercise performance in HF. Emerging data reviewed in this article suggest that the assessment of
circulating myokines (molecules synthesized and secreted by skeletal muscle in response to contraction that
display autocrine, paracrine and endocrine actions) may provide new insights into the pathophysiology, phenotyping
and prognostic stratification of HF-related skeletal myopathy. Further studies are required to determine
whether myokines may also serve as biomarkers to personalize the modality and dose of physical training
prescribed for patients with HF and exercise intolerance. In addition, the production and secretion of myokines in
patients with HF may interact with systemic alterations (e.g., inflammation and metabolic disturbances),
frequently present in patients with HF. Furthermore, myokines may exert beneficial or detrimental effects on
cardiac structure and function, which may influence adverse cardiac remodelling and clinical outcomes in HF
patients. Collectively, these data suggest that a deeper knowledge on myokines regulation and actions may lead
to the identification of novel physical exercise-based therapeutic approaches for HF patients., Instituto de Salud Carlos III (Spain) (CB16/11/00483 to JD, PI18/01469 co-financed by “Fondos Europeos de Desarrollo Regional to AG, CP18/0150 Miguel Servet Fellow to AG-H); Ministerio de Ciencia e Innovación (Spain) (PID2020-113098RB-I00 to MI); European Commission CRUCIAL project (grant agreement 848109 to AG). Open access funding provided by Universidad Pública de Navarra.

Background: Long-COVID-19 syndrome (LCS) exhibits neurological problems such as peripheral neuropathy and autonomic nervous system (ANS) dysfunction. Exercise intolerance and, consequently, low cardiorespiratory fitness (CRF) are some of the most common symptoms of LCS. We describe a series of individuals exhibiting LCS symptoms compared to a control group and posit that this condition may be related to the exercise capacity¿mediated disruption of the ANS resulting particularly in exercise intolerance. Methods: This study included 87 individuals with LCS and 71 control participants without COVID-19 diagnoses. Heart rate variability (HRV) in supine position is commonly measured to diagnose autonomic dysregulation and subsequently analyzed using the Kubios software (Kuopio, Finland). CRF (peak VO2), post-COVID-19 patient-reported symptoms, maximal muscle strength (grip strength, bilateral leg press, leg extension, pectoral press, and back press exercises), and body composition were also measured. Analysis of covariance (ANCOVA) and mediation analysis were employed to assess the associations among LCS, peak VO2, and HRV indicators. Two-sided p < 0.05 was considered as significant. Results: The HRV parameters¿RR interval, RMSSD, SDNN, PNS index, LF, HF, total power, SD1, and SD2¿were significantly elevated (p < 0.05) in the control group when compared to the LCS patients. In contrast, the HR, stress index, and SNS index parameters were significantly higher (p < 0.05) in the LCS group. When adjusted for RR intervals, these parameters remained statistically significant (p < 0.05). A partially mediated effect was found between peak VO2 and RMSSD (mediation effect = 24.4%) as well as peak VO2 and SDNN (mediation effect = 25.1%) in the LCS patients. CONCLUSIONS: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO2 observed in long COVID-19 patients., The EXER-COVID study was supported by the “Proyectos de I+D+i” of the Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, within the framework of the Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RB-I00). They lack the power or authority to impact the gathering, handling, analysis, and interpretation of data; the composition of the report; and the decision to present the report for publication.

Background & aims: Long COVID syndrome (LCS) involves persistent symptoms experienced by many
patients after recovering from coronavirus disease 2019 (COVID-19). We aimed to assess skeletal muscle
energy metabolism, which is closely related to substrate oxidation rates during exercise, in patients with
LCS compared with healthy controls. We also examined whether muscle power output mediates the
relationship between COVID-19 and skeletal muscle energy metabolism.
Methods: In this cross-sectional study, we enrolled 71 patients with LCS and 63 healthy controls. We
assessed clinical characteristics such as body composition, physical activity, and muscle strength. We
used cardiopulmonary exercise testing to evaluate substrate oxidation rates during graded exercise. We
performed statistical analyses to compare group characteristics and peak fat oxidation differences based
on power output.
Results: The two-way analysis of covariance (ANCOVA) results, adjusted for covariates, showed that the
patients with LCS had lower absolute maximal fatty acid oxidation (MFO), relative MFO/fat free mass
(FFM), absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen uptake (V__O2) at
maximum fat oxidation (g min1
) than the healthy controls (P < 0.05). Moderation analysis indicated that
muscle power output significantly influenced the relationship between LCS and reduced peak fat
oxidation (interaction b ¼ 0.105 [95% confidence interval 0.174; 0.036]; P ¼ 0.026). Therefore, when
muscle power output was below 388 W, the effect of the LCS on MFO was significant (62% in our study
sample P ¼ 0.010). These findings suggest compromised mitochondrial bioenergetics and muscle function, represented by lower peak fat oxidation rates, in the patients with LCS compared with the healthy
controls.
Conclusion: The patients with LCS had lower peak fat oxidation during exercise compared with the
healthy controls, potentially indicating impairment in skeletal muscle function. The relationship between
peak fat oxidation and LCS appears to be mediated predominantly by muscle power output. Additional
research should continue investigating LCS pathogenesis and the functional role of mitochondria., The EXER-COVID study was supported by «Proyectos de I+D+i» de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I + D + i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 (PID2020-113098RB-I00)

Aging, a universal and inevitable process, is characterized by a progressive accumulation of physiological alterations and functional decline over time, leading to increased vulnerability to diseases and ultimately mortality as age advances. Lifestyle factors, notably physical activity (PA) and exercise, significantly modulate aging phenotypes. Physical activity and exercise can prevent or ameliorate lifestyle-related diseases, extend health span, enhance physical function, and reduce the burden of non-communicable chronic diseases including cardiometabolic disease, cancer, musculoskeletal and neurological conditions, and chronic respiratory diseases as well as premature mortality.
Physical activity influences the cellular and molecular drivers of biological aging, slowing aging rates¿a foundational aspect of geroscience. Thus, PA serves both as preventive medicine and therapeutic agent in pathological states. Sub-optimal PA levels correlate with increased disease prevalence in aging populations. Structured exercise prescriptions should therefore be customized and monitored like any other medical treatment, considering the dose-response relationships and specific adaptations necessary for intended outcomes. Current guidelines recommend a multifaceted exercise regimen that includes aerobic, resistance, balance, and flexibility training through structured and incidental (integrated lifestyle) activities.
Tailored exercise programs have proven effective in helping older adults maintain their functional capacities, extending their health span, and enhancing their quality of life. Particularly important are anabolic exercises, such as Progressive resistance training (PRT), which are indispensable for maintaining or improving functional capacity in older adults, particularly those with frailty, sarcopenia or osteoporosis, or those hospitalized or in residential aged care. Multicomponent exercise interventions that include cognitive tasks significantly enhance the hallmarks of frailty (low body mass, strength, mobility, PA level, and energy) and cognitive function, thus preventing falls and optimizing functional capacity during aging. Importantly, PA/exercise displays dose-response characteristics and varies between individuals, necessitating personalized modalities tailored to specific medical conditions. Precision in exercise prescriptions remains a significant area of further research, given the global impact of aging and broad effects of PA.
Economic analyses underscore the cost benefits of exercise programs, justifying broader integration into health care for older adults. However, despite these benefits, exercise is far from fully integrated into medical practice for older people. Many healthcare professionals, including geriatricians, need more training to incorporate exercise directly into patient care, whether in settings including hospitals, outpatient clinics, or residential care. Education about the use of exercise as isolated or adjunctive treatment for geriatric syndromes and chronic diseases would do much to ease the problems of polypharmacy and widespread prescription of potentially inappropriate medications. This intersection of prescriptive practices and PA/exercise offers a promising approach to enhance the well-being of older adults. An integrated strategy that combines exercise prescriptions with pharmacotherapy would optimize the vitality and functional independence of older people whilst minimizing adverse drug reactions.
This consensus provides the rationale for the integration of PA into health promotion, disease prevention, and management strategies for older adults. Guidelines are included for specific modalities and dosages of exercise with proven efficacy in randomized controlled trials. Descriptions of the beneficial physiological changes, attenuation of aging phenotypes, and role of exercise in chronic disease and disability management in older adults are provided. The use of exercise in cardiometabolic, Dr. Mikel Izquierdo was supported in part by «Proyectos de I+D+i» de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RB-I00) and by the European Union and Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI), Unión Europea NextGenerationEU/PRTR with number PLEC2021-0080171 and by EU Funded H2020-DIABFRAIL-LATAM (H2020-SC1-BHC-825546). Dr. Fielding was supported in part by the US Department of Agriculture under agreement No. 58-1950-4-003. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA.

Background: the post-COVID-19 condition is a novel condition for which guidelines recommend supervised exercise, but evidence guiding safe and effective interventions is limited. The aim of this study was to investigate the effects of a tailored exercise program (EXER-COVID 5 trial) on cardiorespiratory fitness, muscle strength, long COVID symptoms, cognitive performance, quality of life, depression, and psychological distress. Methods: this crossover study included 100 participants with post-COVID-19 conditions (mean 8 age 48 years; 68% women) at a single center in Spain from March 1, 2021, to September 30, 2022. Participants were randomized 1:1 to 6 weeks of muscle power resistance training (PRT) followed by 6 weeks of usual care (Group 1 [AB], n=50) or 6 weeks of usual care followed by 6 weeks of muscle power RT (Group 2 [BA], n=50). Results: the intervention significantly improved the peak VO2 by 2.10 mL/kg/min [95% CI 1.25 to 2.94], P<0.001. Per-protocol analyses revealed similar results (2.40 mL/kg/min [95% CI 1.56 to 3.25]), P<0.001. No carry-over or period effects were detected. After power PRT, strength (1RM) was improved for pectoral press, bilateral leg-press, knee extension, and back press (P<0.001). Significant decreases were found in psychological distress scores (P<0.001). The intervention also improved quality of life (P=0.041), cognitive capabilities (P=0.014) and cognitive performance (P=0.036). Furthermore, the exercise program reduced seven of the 22 long-COVID symptoms, including weakness (RR= 0.75) dyspnea (RR= 0.56), hearing loss/tinnitus (RR= 0.86), change in appetite (RR= 0.84), memory loss (RR= 0.84), stress (RR= 0.80) and apathy/depression (RR= 0.80), (all Ps<0.05). Conclusions: a supervised 6-week PRT intervention program safely improved cardiorespiratory fitness, strength, and mental health in participants with post-COVID-19 conditions. These findings provide clinicians with evidence to support exercise as standard co-therapy and warrant further study., The EXER-COVID Crossover Study was supported by Proyectos de I+D+i de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 (PID2020-113098RB-I00).

Immersion water sports involve long-term apneas; therefore, athletes must physiologically
adapt to maintain muscle oxygenation, despite not performing pulmonary ventilation.
Breath-holding (i.e., apnea) is common in water sports, and it involves a decrease and
increases PaO2 and PaCO2, respectively, as the primary signals that trigger the end of
apnea. The principal physiological O2 sensors are the carotid bodies, which are able to
detect arterial gases and metabolic alterations before reaching the brain, which aids in
adjusting the cardiorespiratory system. Moreover, the principal H+/CO2 sensor is the
retrotrapezoid nucleus, which is located at the brainstem level; this mechanism contributes
to detecting respiratory and metabolic acidosis. Although these sensors have been
characterized in pathophysiological states, current evidence shows a possible role for
these mechanisms as physiological sensors during voluntary apnea. Divers and swimmer
athletes have been found to displayed longer apnea times than land sports athletes, as well
as decreased peripheral O2 and central CO2 chemoreflex control. However, although
chemosensitivity at rest could be decreased, we recently found marked
sympathoexcitation during maximum voluntary apnea in young swimmers, which could
activate the spleen (which is a reservoir organ for oxygenated blood). Therefore, it is
possible that the chemoreflex, autonomic function, and storage/delivery oxygen organ(s)
are linked to apnea in immersion water sports. In this review, we summarized the available
evidence related to chemoreflex control in immersion water sports. Subsequently, we
propose a possible physiological mechanistic model that could contribute to providing
new avenues for understanding the respiratory physiology of water sports., This study was supported by Minera Escondida Ltda. MEL2203; the Agencia Nacional de Investigación y Desarrollo (ANID), through Fondecyt de Iniciación #11220870 and Anillo ACT210083. MI was funded in part by grant from the Spanish Ministry of Economy, Ministerio
de Ciencia e Innovación (PID 2020-113098RB-I00).

The presence of persistent coronavirus disease 2019 (COVID-19) might beassociated with significant levels of psychological distress that would meet thethreshold for clinical relevance. The Center for Epidemiologic Studies DepressionScale (CES-D) version 10 has been widely used in assessing psychological distressamong general and clinical populations from different cultural backgrounds. To ourknowledge, however, researchers have not yet validated these findings amongpatients with persistent COVID-19. A cross-sectional validation study wasconducted with 100 patients from the EXER-COVID project (69.8% women;mean (±standard deviation) ages: 47.4 ± 9.5 years). Confirmatory factor analyses(CFAs) were performed on the 10-item CES-D to test four model fits: (a)unidimensional model, (b) two-factor correlated model, (c) three-factor correlatedmodel, and (d) second-order factor model. The diagonal-weighted least-squares estimator was used, as it is commonly applied to latent variable modelswith ordered categorical variables. The reliability indices of the 10-item CES-D in patients with persistent COVID-19 were as follows: depressive affect factor(α=0.82Ord;ω=0.78u−cat), somatic retardation factor (α=0.78Ord;ω=0.56u−cat),and positive affect factor (α=0.56Ord;ω=0.55u−cat). The second‐order model fitshowed good Omega reliability (ω=0.87ho). Regarding CFAs, the unidimensional‐factor model shows poor goodness of fit, especially residuals analysis (root meansquare error of approximation [RMSEA] = 0.081 [95% confidence interval,CI = 0.040–0.119]; standardized root mean square residual [SRMR] = 0.101). The two‐factor correlated model, three‐factor correlated model, and second‐order factormodel showed adequate goodness of fit, and theχ2difference test (∆X2) did not show significant differences between the goodness of fit for these models(∆X= 4.11282;p= 0.127). Several indices showed a good fit with the three‐factor correlated model: goodness‐of‐fit index = 0.974, comparative fit index = 0.990,relative noncentrality index = 0.990, and incremental fit index = 0.990, which were all above 0.95, the traditional cut‐off establishing adequate fit. On the other hand RMSEA = 0.049 (95% CI = 0.000–0.095), where an RMSEA < 0.06–0.08 indicates anadequate fit. Item loadings on the factors were statistically significant (λ≥0.449j;p's < 0.001), indicating that the items loaded correctly on the corresponding factors and the relationship between factors (φ≥0.382;p's≤0.001. To our knowledge, thisis the first study to provide validity and reliability to 10‐item CES‐D in a persistentCOVID‐19 Spanish patient sample. The validation and reliability of this shortscreening tool allow us to increase the chance of obtaining complete data in aparticular patient profile with increased fatigue and brain fog that limit patients' capacity to complete questionnaires., The EXER‐COVID study was supported by “Proyectos de I+D+i” de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientadaa los Retos de la Sociedad, en el marco del Plan Estatal deInvestigación Científica y Técnica y de Innovación 2017‐2020(PID2020‐113098RB‐I00). Open access funding provided by Uni-versidad Pública de Navarra.

As the global population continues to age, an urgent question arises:
how can we improve the quality of life for older adults while reducing the
burden of age-related diseases and disabilities? A growing body of
evidence suggests that evidence-based exercise, used as both preventive
and therapeutic medicine, may hold the key to extending healthy
As the global population continues to age, an urgent question arises: howcanweimprovethequalityoflifeforolderadultswhilereducingthe burden of age-related diseases and disabilities? A growing body of evidence suggests that evidence-based exercise, used as both preventive and therapeutic medicine, may hold the key to extending healthy longevity, preventing chronic conditions, and preserving physical and cognitive function. The “Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR)” emphasizes the importance of integrating tailored exercise regimens into geriatric care, positioning exercise not only as preventive medicine but also as a therapeutic cornerstone in managing age-related decline. The updated consensus document introduces several advancements that distinguish it from the previous consensus published a few years ago. It emphasizes more personalized, evidence-based exercise prescriptions that align with individual health profiles and conditions, moving beyond genericactivityguidelines., Prof. Mikel Izquierdo was supported in part by «Proyectos de I+D+i» de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RBI00) and by the European Union and Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI), Unión Europea NextGenerationEU/PRTR with number PLEC2021-0080171 and by EU Funded H2020-DIABFRAIL-LATAM (H2020-SC1-BHC-825546).

Background. Physical exercise improves mental and physical health of individuals with severe mental illness (SMI); however, its impact on metabolic syndrome remains unclear.
Aims. To evaluate the effects of exercise interventions on metabolic syndrome components in individuals with SMI and explore interactions between exercise and antipsychotic medications on metabolic outcomes.
Methods. Following PRISMA guidelines, we systematically searched PubMed, CINAHL, Web of Science, and APA PsycINFO through October 10, 2023, for randomized controlled trials (RCTs) assessing the effects of exercise on waist circumference, blood pressure, glucose, triglycerides, and HDL cholesterol in SMI. Risk of bias was evaluated using the Cochrane RoB-2 tool. Data were pooled using random-effects models in Comprehensive Meta-Analysis and JASP.
Results. Ten RCTs (N = 773; mean age 39.9 ± 7.36 years; 38.7% female; 71.5% schizophrenia spectrum disorders) met inclusion criteria. Pooled analyses revealed no significant effects of exercise on waist circumference (SMD = 0.206, 95% CI [-0.118, 0.530], p = 0.171), systolic blood pressure (SMD = 0.194, 95% CI [-0.115, 0.504], p = 0.219), diastolic blood pressure (SMD = -0.21, 95% CI [-0.854, 0.434], p = 0.522), HDL (SMD = 0.157, 95% CI [-0.36, 0.674], p = 0.551), triglycerides (SMD = -0.041, 95% CI [-0.461, 0.38], p = 0.849), or glucose (SMD = -0.071, 95% CI [-0.213, 0.071], p = 0.326). Heterogeneity was moderate to high.
Conclusions. Exercise interventions did not significantly improve metabolic syndrome components in SMI. Future trials must prioritize tailored regimens, adjunctive therapies, and rigorous control of medication effects., Prof. Mikel Izquierdo was supported in part by “Proyectos de I + D + i”» de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I + D + i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 (PID2020-113098RB-I00) and by the European Union and Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI), Unión Europea NextGenerationEU/PRTR with number PLEC2021-0080171 and by EU Funded H2020-DIABFRAIL-LATAM (H2020-SC1-BHC-825546).

Background: acute hospitalisation is a recognised risk factor for adverse outcomes in older adults, including hospital-associated disability. Post-discharge exercise interventions might mitigate physical and cognitive decline, although the few meta-analyses performed previously present limitations. This systematic review and meta-analysis aimed to evaluate the effect of post-discharge exercise interventions on health-related outcomes in older adults.
Methods: a systematic search of PubMed, Scopus, Web of Science, and ScienceDirect was conducted following PRISMA 2020 guidelines on May 16, 2025. Randomised controlled trials published from Jan 1, 2000, to May 16, 2025, were included. These studies assessed the effectiveness of muscular strength and endurance exercises in older adults (aged 60 years and older) discharged from acute hospitalisation. There were no language filters. Two reviewers independently screened studies using the PICOS framework, extracted data from published reports, and assessed methodological quality using the Physiotherapy Evidence Database scale. Data were pooled using a random-effects model. This systematic review and meta-analysis is registered with PROSPERO, CRD42025630147.
Findings: the search yielded 2868 results, of which 17 articles (1458 participants) met inclusion criteria, with a mean Physiotherapy Evidence Database score of 7·3 (SD 0·9) out of 10, indicating moderate to high quality. Post-discharge exercise significantly improved physical function (standardised mean difference [SMD] 0·78 [95% CI 0·52 to 1·05], p<0·0001). No significant effects were observed for health-related quality of life (SMD 0·23 [−0·04 to 0·51], p=0·098) or readmission risk (risk ratio 0·64 [95% CI 0·39 to 1·05], p=0·076). Exercise effects on functional independence, cognitive function, frailty, and mortality were synthesised descriptively due to insufficient data for meta-analysis. The main sources of heterogeneity were the outcome assessment tools and the exercise protocols. No evidence of risk of bias was found using either selection models (p>0·05) or Egger’s test (p>0·05) for any of the outcomes.
Interpretation: post-discharge exercise interventions are effective at improving physical function in older adults following acute hospitalisation; however, effects on other health-related outcomes remain inconclusive. Future studies should establish optimal post-discharge exercise modalities, dosages, and delivery strategies tailored to individual patient needs. Advancing these priorities could improve patient outcomes and health-care system efficiency., MI was supported in part by R&D&I Projects of the State Programme for Knowledge Generation and Scientific and Technological Strengthening of the R&D&I System, within the framework of the Spanish State Plan for Scientific and Technical Research and Innovation 2017-20 (PID2020-113098RBI00); and by the EU Ministry of Science and Innovation NextGenerationEU Recovery, Transformation and Resilience Plan (PLEC2021-0080171) and Horizon 2020 Diabetes and Frailty in LatinAmerica Project (H2020-SC1-BHC-825546).

Esta tesis doctoral se basa en la línea de base del proyecto EXER-COVID study proyecto financiado por Proyectos de I+D+i de Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, dentro del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RBI00).
El objetivo general del presente estudio fue evaluar la condición física de pacientes con síntomas persistentes de COVID-19 en Pamplona-Navarra y compararla con la de un grupo control de personas sanas, pertenecientes cohorte de vigilancia epidemiológica de enfermedades crónicas no trasmisibles, adscrito al centro de investigación biomédica del Gobierno de Navarra (Navarrabiomed) y al Hospital Universitario de Navarra (HUN), dentro de los proyectos estratégicos de I+D 2019-2021 en el reto GEMA de Genómica y Medicina Avanzada, estrategia navarra en medicina genómica aplicada a hipercolesterolemia (NAGENCOL) (PI_2019/39). Con este fin, se analizaron específicamente la eficiencia ventilatoria, la fuerza muscular del tren superior e inferior, la función autonómica y el metabolismo oxidativo de los pacientes, contrastando estos parámetros con los obtenidos en individuos sanos. Esta Tesis Doctoral se compone de cuatro estudios publicados en revistas científicas internacionales. A continuación, se resumen los resultados más pertinentes:
Capítulo 1: Eficiencia ventilatoria en respuesta al ejercicio máximo en pacientes con síndrome persistente de COVID-19: un estudio transversal. Conclusiones: Considerando el papel central de la capacidad de ejercicio en pacientes con COVID-19 persistente, la rehabilitación física podría ser fundamental en esta situación nueva y poco conocida. Por lo tanto, es esencial establecer estrategias con programas multicomponentes para optimizar la recuperación en estos pacientes.
Capítulo 2: La reducción de la fuerza muscular en pacientes con síndrome de COVID-19 prolongado está mediada por la masa muscular de las extremidades. Conclusiones: Nuestros hallazgos proporcionan nuevas perspectivas sobre los mecanismos subyacentes a la relación entre el síndrome de COVID prolongado y los niveles de fuerza de agarre/extensión de pierna, respaldando los efectos negativos del síndrome de COVID prolongado sobre la función muscular.
Capítulo 3: La capacidad oxidativa máxima durante el ejercicio está asociada con la producción de potencia muscular en pacientes con síndrome de COVID-19 prolongado. Un análisis de moderación. Conclusión: Los pacientes con LCS presentaron una oxidación máxima de grasa más baja durante el ejercicio en comparación con los controles sanos, lo que posiblemente indique un deterioro en la función muscular esquelética. La relación entre la oxidación máxima de grasa y el LCS parece estar mediada predominantemente por la producción de potencia muscular. Se debe continuar investigando la patogénesis del LCS y el papel funcional de las mitocondrias.
Capítulo 4: La función autonómica reducida en pacientes con síndrome de COVID-19 prolongado está mediada por la aptitud cardiorrespiratoria. Conclusiones: Estos hallazgos aportan nuevas perspectivas sobre la interacción entre la ACR y los indicadores de VFC, y sugieren que la disautonomía podría estar relacionada con el bajo VO2 pico observado en los pacientes con COVID-19 prolongado., This Doctoral Thesis is based on the baseline data from the EXER-COVID study project, funded by the Proyectos de I+D+i de Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, dentro del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RB-I00). The general objective of this study was to evaluate the physical condition of patients with persistent COVID-19 symptoms in Pamplona-Navarra and to compare it with that of a control group of healthy individuals from the epidemiological surveillance cohort for non-communicable chronic diseases. This cohort is associated with the Biomedical Research Center of the Government of Navarre (Navarrabiomed) and the University Hospital of Navarre (HUN), under the 2019-2021 strategic R&D projects within the GEMA challenge on Genomics and Advanced Medicine, the Navarrese strategy in genomic medicine applied to hypercholesterolemia (NAGENCOL) (PI_2019/39). To this end, the study specifically analyzed ventilatory efficiency, upper and lower body muscle strength, autonomic function, and oxidative metabolism in patients, comparing these parameters with those obtained from healthy individuals. This Doctoral Thesis comprises four studies published in international scientific journals. The following summarizes the most relevant results:
Chapter 1: Ventilatory efficiency in response to maximal exercise in persistent COVID-19 syndrome patients: a cross-sectional study. Conclusions: Considering the central role of exercise capacity in patients with persistent COVID-19, exercise rehabilitation could be fundamental in this new and little-known situation. Therefore, it is essential to establish strategies with multicomponent programs, to optimize recovery in these patients.
Chapter 2: Reduced muscle strength in patients with long-COVID-19 syndrome is mediated by limb muscle mass. Conclusions: Our findings provide novel insights into the mechanisms underlying the relationship between long-COVID syndrome and grip/leg strength levels, supporting the negative effects of long-COVID syndrome on muscle function.
Chapter 3: Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation análisis. Conclusion: The patients with LCS had lower peak fat oxidation during exercise compared with the healthy controls, potentially indicating impairment in skeletal muscle function. The relationship between peak fat oxidation and LCS appears to be mediated predominantly by muscle power output. Additional research should continue investigating LCS pathogenesis and the functional role of mitochondria.
Chapter 4: Reduced autonomic function in patients with long-COVID-19
syndrome is mediated by cardiorespiratory fitness. Conclusions: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO2 observed in long COVID-19 patients., The EXER-COVID study was supported by the Proyectos de I+D+i of the Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i Orientada a los Retos de la Sociedad, within the framework of the Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2020-113098RB-I00)., Programa de Doctorado en Ciencias de la Salud (RD 99/2011), Osasun Zientzietako Doktoretza Programa (ED 99/2011)