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The Physiological Mechanisms of the Sex-Based Difference in Outcomes of COVID19 Infection.

ABSTRACT: The scale of the SARS-CoV-2 pandemic has thrust a spotlight on the sex-based differences in response to viral diseases; morbidity and mortality are greater in men than women. We outline the mechanisms by which being female offers a degree of protection from COVID19, that persists even when confounders such as comorbidities are considered. The physiological and immunological mechanisms are fascinating and range from incomplete X chromosome inactivation of immune genes, a crucial role for angiotensin converting enzyme 2 (ACE2), and regulation of both immune activity and ACE2 by sex steroids. From this flows understanding of why lung and other organs are more susceptible to COVID19 damage in men, and how their distinct immunological landscapes need to be acknowledged to guide prognosis and treatment. Pregnancy, menopause, and hormone replacement therapy bring changed hormonal environments and the need for better stratification in COVID19 studies. We end by noting clinical trials based on increasing estrogens or progesterone or anti-testosterone drugs; excellent examples of translational physiology.

SUBMITTER: Wray S

PROVIDER: S-EPMC7900431 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The Physiological Mechanisms of the Sex-Based Difference in Outcomes of COVID19 Infection.

Wray Susan S Arrowsmith Sarah S

Frontiers in physiology 20210209

The scale of the SARS-CoV-2 pandemic has thrust a spotlight on the sex-based differences in response to viral diseases; morbidity and mortality are greater in men than women. We outline the mechanisms by which being female offers a degree of protection from COVID19, that persists even when confounders such as comorbidities are considered. The physiological and immunological mechanisms are fascinating and range from incomplete X chromosome inactivation of immune genes, a crucial role for angioten ...[more]

PMID: 33633588

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Project description:While the effect of a variety of exercises on postural balance control has been extensively studied, less attention has been paid to those requiring sport-specific skills. Therefore there is a need to analyze the literature and elucidate changes in postural balance control after exercises performed in conditions close to a particular sport. This scoping review aims (i) To map the literature that addresses postural sway aspects of acute responses to general and sport-specific exercises and their underlying physiological mechanisms, and (ii) To identify gaps in the existing literature and propose future research on this topic. The main literature search conducted on MEDLINE, Web of Science, Scopus, PubMed, and Cochrane Library databases was completed by SpringerLink, Elsevier, and Google Scholar. A total of 60 articles met the inclusion criteria. Findings identified that among a variety of studies evaluating the effects of exercise on postural balance control, only few of them were conducted under sport-specific conditions (i.e., while shooting in biathlon or pentathlon, and after simulated or match-induced protocols in combat and team sports). Therefore, more research is still needed to address this gap in the literature and aim research at investigation of postural sway response to sport-specific exercises. Further analysis of the literature showed that the type, intensity and duration of exercise play a key role in increased postural sway. Whole body and localized muscular fatigue of the trunk, neck and lower limbs is considered to be a main factor responsible for the magnitude of balance impairment in an initial phase of recovery and speed of its readjustment to a pre-exercise level. Other likely factors affecting postural stability are hyperventilation and deterioration of sensorimotor functions, though some contribution of muscle damage, dehydration, hyperthermia or dizziness cannot be excluded. A better understanding of the physiological mechanisms of balance impairment after exercises performed under simulated fatigue induced protocol, close to conditions specific to a particular sport, has implications for designing smart exercise programs tailored to individual needs to improve athlete performance with high demands on postural stability and/or decrease their risk of injuries.

Project description:BackgroundMechanisms of sex-based differences in outcomes following cardiac resynchronization therapy (CRT) are poorly understood.ObjectiveTo use cardiac magnetic resonance (CMR) to define mechanisms of sex-based differences in outcomes after CRT and describe distinct CMR-based phenotypes of CRT candidates based on sex and non-ischemic/ischemic cardiomyopathy type.Materials and methodsIn a prospective study, sex-based differences in three short-term CRT response measures [fractional change in left ventricular end-systolic volume index 6 months after CRT (LVESVI-FC), B-type natriuretic peptide (BNP) 6 months after CRT, change in peak VO2 6 months after CRT], and long-term survival were evaluated with respect to 39 baseline parameters from CMR, exercise testing, laboratory testing, electrocardiograms, comorbid conditions, and other sources. CMR was also used to quantify the degree of left-ventricular mechanical dyssynchrony by deriving the circumferential uniformity ratio estimate (CURE-SVD) parameter from displacement encoding with stimulated echoes (DENSE) strain imaging. Statistical methods included multivariable linear regression with evaluation of interaction effects associated with sex and cardiomyopathy type (ischemic and non-ischemic cardiomyopathy) and survival analysis.ResultsAmong 200 patients, the 54 female patients (27%) pre-CRT had a smaller CMR-based LVEDVI (p = 0.04), more mechanical dyssynchrony based on the validated CMR CURE-SVD parameter (p = 0.04), a lower frequency of both late gadolinium enhancement (LGE) and ischemic cardiomyopathy (p < 0.0001), a greater RVEF (p = 0.02), and a greater frequency of LBBB (p = 0.01). After categorization of patients into four groups based on cardiomyopathy type (ischemic/non-ischemic cardiomyopathy) and sex, female patients with non-ischemic cardiomyopathy had the lowest CURE-SVD (p = 0.003), the lowest pre-CRT BNP levels (p = 0.01), the lowest post-CRT BNP levels (p = 0.05), and the most favorable LVESVI-FC (p = 0.001). Overall, female patients had better 3-year survival before adjustment for cardiomyopathy type (p = 0.007, HR = 0.45) and after adjustment for cardiomyopathy type (p = 0.009, HR = 0.67).ConclusionCMR identifies distinct phenotypes of female CRT patients with non-ischemic and ischemic cardiomyopathy relative to male patients stratified by cardiomyopathy type. The more favorable short-term response and long-term survival outcomes in female heart failure patients with CRT were associated with lower indexed CMR-based LV volumes, decreased presence of scar associated with prior myocardial infarction and ICM, and greater CMR-based dyssynchrony with the CURE-SVD.

Dataset Information

The Physiological Mechanisms of the Sex-Based Difference in Outcomes of COVID19 Infection.

Publications

The Physiological Mechanisms of the Sex-Based Difference in Outcomes of COVID19 Infection.

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