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).

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 & 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)

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.