Molecular mechanisms of sex bias differences in COVID-19 mortality.
Ontology highlight
ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC7347256 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
Molecular mechanisms of sex bias differences in COVID-19 mortality.
Li Yuchong Y Jerkic Mirjana M Slutsky Arthur S AS Zhang Haibo H
Critical care (London, England) 20200709 1
More men than women have died from COVID-19. Genes encoded on X chromosomes, and sex hormones may explain the decreased fatality of COVID-19 in women. The angiotensin-converting enzyme 2 gene is located on X chromosomes. Men, with a single X chromosome, may lack the alternative mechanism for cellular protection after exposure to SARS-CoV-2. Some Toll-like receptors encoded on the X chromosomes can sense SARS-CoV-2 nucleic acids, leading to a stronger innate immunity response in women. Both estro ...[more]
Similar Datasets
Project description:Men are consistently overrepresented in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and coronavirus disease 2019 (COVID-19) severe outcomes, including higher fatality rates. These differences are likely due to gender-specific behaviors, genetic and hormonal factors, and sex differences in biological pathways related to SARS-CoV-2 infection. Several social, behavioral, and comorbid factors are implicated in the generally worse outcomes in men compared with women. Underlying biological sex differences and their effects on COVID-19 outcomes, however, have received less attention. The present review summarizes the available literature regarding proposed molecular and cellular markers of COVID-19 infection, their associations with health outcomes, and any reported modification by sex. Biological sex differences characterized by such biomarkers exist within healthy populations and also differ with age- and sex-specific conditions, such as pregnancy and menopause. In the context of COVID-19, descriptive biomarker levels are often reported by sex, but data pertaining to the effect of patient sex on the relationship between biomarkers and COVID-19 disease severity/outcomes are scarce. Such biomarkers may offer plausible explanations for the worse COVID-19 outcomes seen in men. There is the need for larger studies with sex-specific reporting and robust analyses to elucidate how sex modifies cellular and molecular pathways associated with SARS-CoV-2. This will improve interpretation of biomarkers and clinical management of COVID-19 patients by facilitating a personalized medical approach to risk stratification, prevention, and treatment.
| S-EPMC7402208 | biostudies-literature
Project description:IntroductionSince the first reports of COVID-19 cases, sex-discrepancies have been reported in COVID-19 mortality. We provide a detailed description of these sex differences in relation to age and comorbidities among notified cases as well as in relation to age and sex-specific mortality in the general Dutch population.MethodsData on COVID-19 cases and mortality until May 31st 2020 was extracted from the national surveillance database with exclusion of healthcare workers. Association between sex and case fatality was analyzed with multivariable logistic regression. Subsequently, male-female ratio in standardized mortality ratios and population mortality rates relative to all-cause and infectious disease-specific mortality were computed stratified by age.ResultsMale-female odds ratio for case fatality was 1.33 [95% CI 1.26-1.41] and among hospitalized cases 1.27 [95% CI 1.16-1.40]. This remained significant after adjustment for age and comorbidities. The male-female ratio of the standardized mortality ratio was 1.70 [95%CI 1.62-1.78]. The population mortality rate for COVID-19 was 35.1 per 100.000, with a male-female rate ratio of 1.25 (95% CI 1.18-1.31) which was higher than in all-cause population mortality and infectious disease mortality.ConclusionOur study confirms male sex is a predisposing factor for severe outcomes of COVID-19, independent of age and comorbidities. In addition to general male-female-differences, COVID-19 specific mechanisms likely contribute to this mortality discrepancy.
| S-EPMC9151564 | biostudies-literature
Project description:Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (COVID-19) across the world revealed a distinct sex bias in the disease morbidity as well as the mortality - both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce; however, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.
| S-EPMC8353216 | biostudies-literature
Project description:AimTo examine the magnitude of sex differences in survival from the coronavirus disease 2019 (COVID-19) in Europe across age groups and regions. We hypothesized that men have a higher mortality than women at any given age but that sex differences will decrease with age as only the healthiest men survive to older ages.MethodsWe used population data from the Institut National D'Études Démographiques on cumulative deaths due to COVID-19 from February to June 2020 in 10 European regions: Denmark, Norway, Sweden, The Netherlands, England and Wales, France, Germany, Italy, Spain and Portugal. For each region, we calculated cumulative mortality rates stratified by age and sex and corresponding relative risks for men vs. women.ResultsThe relative risk of dying from COVID-19 was higher for men than for women in almost all age groups in all regions. The overall relative risk ranged from 1.11 (95% confidence interval, CI 1.01-1.23) in Portugal to 1.54 (95% CI 1.49-1.58) in France. In most regions, sex differences increased until the ages of 60-69 years, but decreased thereafter with the smallest sex difference at age 80+ years.ConclusionDespite variability in data collection and time coverage among regions, the study showed an overall similar pattern of sex differences in COVID-19 mortality in Europe.
| S-EPMC7755064 | biostudies-literature
Project description:Aim: To examine the magnitude of sex differences in survival from the Coronavirus Disease 2019 (COVID-19) in Europe across age and countries. We hypothesise that men have higher mortality than women at any given age, but that sex differences will decrease with age as only the strongest men survive to older ages. Methods: We used population data from Institut National D'Études Démographiques on cumulative deaths due to COVID-19 from February to June 2020 in 10 European countries: Denmark, Norway, Sweden, The Netherlands, England & Wales, France, Germany, Italy, Spain and Portugal. For each country, we calculated cumulative mortality rates stratified by age and sex and corresponding relative risks for men vs. women. Results: The relative risk of dying from COVID-19 was higher for men than for women in almost all age groups in all countries. The overall relative risk ranged from 1.11 (95% CI 1.01-1.23) in Portugal to 1.54 (95% CI 1.49-1.58) in France. In most countries, sex differences increased until ages 60-69 years, but decreased thereafter with the smallest sex difference at ages 80+. Conclusions: Despite variability in data collection and time coverage among countries, we illustrate an overall similar pattern of sex differences in COVID-19 mortality in Europe.
| S-EPMC7444295 | biostudies-literature
Project description:Gender-specific differences in thrombosis have been reported in hospitalized patients with COVID-19. We sought to investigate the influence of age on the relation between gender and incident thrombosis or death in COVID-19. We identified consecutive adults aged ≥18 years hospitalized with COVID-19 from March 1, 2020, to April 17, 2020, at a large New York health system. In-hospital thrombosis and all-cause mortality were evaluated by gender and stratified by age group. Logistic regression models were generated to estimate the odds of thrombosis or death after multivariable adjustment. In 3,334 patients hospitalized with COVID-19, 61% were men. Death or thrombosis occurred in 34% of hospitalizations and was more common in men (36% vs 29% in women, p <0.001; adjusted odds ratio [aOR] 1.61, 95% confidence interval [CI] 1.36 to 1.91). When stratified by age, men had a higher incidence of death or thrombosis in younger patients (aged 18 to 54 years: 21% vs 9%, aOR 3.17, 95% CI 2.06 to 5.01; aged 55 to 74 years: 39% vs 28%, aOR 1.63, 95% CI 1.28 to 2.10), but not older patients (aged ≥75 years: 55% vs 48%; aOR 1.20, 95% CI 0.90 to 1.59) (interaction p value: 0.01). For the individual end points, men were at higher risk of thrombosis (19% vs 12%; aOR 1.65, 95% CI 1.33 to 2.05) and mortality (26% vs 23%; aOR 1.41, 95% CI 1.17 to 1.69) than women, and gender-specific differences were attenuated with older age. Associations between thrombosis and mortality were most striking in younger patients (aged 18 to 54 years, aOR 8.25; aged 55 to 74 years, aOR 2.38; aged >75 years, aOR 1.88; p for interaction <0.001) but did not differ by gender. In conclusion, the risk of thrombosis or death in COVID-19 is higher in men compared with women and is most apparent in younger age groups.
| S-EPMC8908016 | biostudies-literature
Project description:BackgroundThere is a worrying lack of epidemiological data on the sex differential in COVID-19 infection and death rates between the regions of Peru.MethodsUsing cases and death data from the national population-based surveillance system of Peru, we estimated incidence, mortality and fatality, stratified by sex, age and geographic distribution (per 100,000 habitants) from March 16 to November 27, 2020. At the same time, we calculated the risk of COVID-19 death.ResultsDuring the study period, 961894 cases and 35913 deaths were reported in Peru. Men had a twofold higher risk of COVID-19 death within the overall population of Peru (odds ratio (OR), 2.11; confidence interval (CI) 95%; 2.06-2.16; p<0.00001), as well as 20 regions of Peru, compared to women (p<0.05). There were variations in incidence, mortality and fatality rates stratified by sex, age, and region. The incidence rate was higher among men than among women (3079 vs. 2819 per 100,000 habitants, respectively). The mortality rate was two times higher in males than in females (153 vs. 68 per 100,000 habitants, respectively). The mortality rates increased with age, and were high in men 60 years of age or older. The fatality rate was two times higher in men than in women (4.96% vs. 2.41%, respectively), and was high in men 50 years of age or older.ConclusionsThese findings show the higher incidence, mortality and fatality rates among men than among women from Peru. These rates vary widely by region, and men are at greater risk of COVID-19 death. In addition, the mortality and fatality rates increased with age, and were most predominant in men 50 years of age or older.
| S-EPMC8202928 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.
| S-EPMC7498997 | biostudies-literature
Project description:Cardiovascular disease (CVD) is still the leading cause of illness and death in the Western world. Cardiovascular aging is a progressive modification occurring in cardiac and vascular morphology and physiology where increased endothelial dysfunction and arterial stiffness are observed, generally accompanied by increased systolic blood pressure and augmented pulse pressure. The effects of biological sex on cardiovascular pathophysiology have long been known. The incidence of hypertension is higher in men, and it increases in postmenopausal women. Premenopausal women are protected from CVD compared with age-matched men and this protective effect is lost with menopause, suggesting that sex-hormones influence blood pressure regulation. In parallel, the heart progressively remodels over the course of life and the pattern of cardiac remodeling also differs between the sexes. Lower autonomic tone, reduced baroreceptor response, and greater vascular function are observed in premenopausal women than men of similar age. However, postmenopausal women have stiffer arteries than their male counterparts. The biological mechanisms responsible for sex-related differences observed in cardiovascular aging are being unraveled over the last several decades. This review focuses on molecular mechanisms underlying the sex-differences of CVD in aging.
| S-EPMC9261391 | biostudies-literature
Project description:BackgroundThe differential effect of comorbidities on COVID-19 severe outcomes by sex has not been fully evaluated.ObjectiveTo examine the association of major comorbidities and COVID-19 mortality in men and women separately.MethodsWe performed a retrospective cohort analysis using a large electronic health record (EHR) database in the U.S. We included adult patients with a clinical diagnosis of COVID-19 who also had necessary information on demographics and comorbidities from January 1, 2016 to October 31, 2021. We defined comorbidities by the Charlson Comorbidity Index (CCI) using ICD-10 codes at or before the COVID-19 diagnosis. We conducted logistic regressions to compare the risk of death associated with comorbidities stratifying by sex.ResultsA total of 121,342 patients were included in the final analysis. We found significant sex differences in the association between comorbidities and COVID-19 death. Specifically, moderate/severe liver disease, dementia, metastatic solid tumor, and heart failure and the increased number of comorbidities appeared to confer a greater magnitude of mortality risk in women compared to men.ConclusionsOur study suggests sex differences in the effect of comorbidities on COVID-19 mortality and highlights the importance of implementing sex-specific preventive or treatment approaches in patients with COVID-19.
| S-EPMC9412184 | biostudies-literature