Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis (original) (raw)
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Evidence for treatment with estradiol for women with SARS-CoV-2 infection
2020
Background Given that an individual’s age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options? Methods An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15–49 years) and peri-/post-menopausal (> 50 years). Results The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is higher in women than men (by about + 15%) and, in contrast, the fatality rate is higher in men (about + 50%). Interestingly, the relationships between these quantities are linked to age: pre-adolescent girls and boys had the ...
Is the Severity of SARS CoV2 Infection Dependent on the Patient’s Gender?
ARS Medica Tomitana
Objective: The COVID 19 pandemic has been the biggest health problem in the last 2 years, exerting huge pressure on the global healthcare system. Studies showed a predisposition in men to develop more severe forms, with a higher mortality rate, in comparison to women. Also, men infected with SARS CoV2 would be at higher risk of hospitalization in acute intensive care units (ICU) with complications that could lead to death Methods: We conducted a retrospective cross-sectional study that included 177 hospitalized patients in a time frame of 18 months with SARS CoV2 infection confirmed by RT PCR testing in the Pneumology Department of the Clinical Hospital of Pneumophtisiology of Constanta, Romania. The information needed to conduct the study was gathered from the patient’s general clinical observation sheet and included: the smoker/ non-smoker status of the patient, age, symptoms associated with COVID19 infection, biological data, form of disease, treatment administered during hospita...
Journal of Medical Virology, 2021
Biological sex could affect the natural history of severe acute respiratory syndrome coronavirus 2 infection. We enrolled all COVID-19 patients admitted to two COVID-19 hospitals in Milan in a prospective observational study. The primary outcome was death during the study period and the secondary outcome was critical disease at hospital admission. The association(s) between clinically relevant, noncollinear variables, and the primary outcome was assessed with uni-and multivariable Logistic regression models. A total of 520 patients were hospitalized of whom 349 (67%) were males with a median age 61 (interquartile range: 50-72). A higher proportion of males presented critically ill
Encyclopedia
The existence of differences in susceptibility to SARS-CoV-2 infection between males and females in both incidence and outcomes is well documented in the scientific literature. These differences, which are still underestimated, may have important implications in terms of prevention, diagnosis, and treatment of COVID-19, with significant prognostic consequences. The greater severity of the infection observed in males, even more so if they are elderly, would seem, according to current knowledge, to be due to multiple influences: immunological and endocrinological, but also genetic and behavioral.
Journal of Personalized Medicine
Vaccine-induced immunity is a key strategy in the long-term control of the COVID-19 pandemic. The aim of our study was to explore the relationship between mRNA vaccine-induced antibodies and gender-sensitive variables among healthcare workers. Two thousand-sixty-five volunteers who received the BNT162b2 vaccine were enrolled in the study and followed up. Demographic, clinical, and social variables (educational level, marital status, occupation, childcare) were evaluated through a self-administered questionnaire. Anti-Spike (S) IgG were measured at 1 month (T1) and at 5 months (T2) after the second vaccine dose. At T1, median anti-S IgG values were 693 [394–>800] AU/mL (1 AU = 2.6 BAU). Values > 800 AU/mL (2080 BAU/mL) were directly associated with a previous COVID-19 (p < 0.001) infection and inversely with age (p < 0.001), smoking habit (p < 0.001), and autoimmune diseases (p < 0.001). At T2, a significant decreasing in anti-S IgG values was observed (187 [81–262]...
Sex-derived attributes contributing to SARS-CoV-2 mortality
American Journal of Physiology-Endocrinology and Metabolism, 2020
Epidemiological data in COVID-19 mortality indicate that men are more prone to die of SARS-CoV-2 infection than women, but biological causes for this sexual dimorphism are unknown. We discuss the prospective behavioral and biological differences between the sexes that could be attributed to this sex-based differentiation. The female sex hormones and the immune stimulatory genes, including Toll-like receptors, interleukins, and micro-RNAs present on X-chromosome, may impart lesser infectivity and mortality of the SARS-CoV-2 in females over males. The sex hormone estrogen interacts with the renin-angiotensin-aldosterone system, one of the most critical pathways in COVID-19 infectivity, and modulates the vasomotor homeostasis. Testosterone on the contrary enhances the levels of the two most critical molecules, angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine-type 2 (TMPRSS2), transcriptionally and posttranslationally, thereby increasing viral load and delayi...
An overview of sex hormones in relation to SARS-CoV-2 infection
Future Virology, 2021
Aim: Sex differences in COVID-19 outcomes might be explained from a sex hormones (SexHs) perspective. Materials & methods: PubMed, Scopus, Web of Science, EMBASE and Google Scholar were searched up to March 2021. Results: Based on the literature review, the crosstalk between SexHs (estrogens, progesterone and testosterone), their receptors (estrogen α and β, androgen, and progesterone) and the immune system shaped the sex-related differences in immune responses against COVID-19. Differential production of SexHs over the lifespan (during pregnancy, reproductive years, menopause and andropause) and over different seasons may result in disparities in body response toward COVID-19. Moreover, SexHs-specific differences might affect vaccine efficacy and response to treatment. Conclusion: The roles of SexHs need to be considered in vaccine development and even treatment of COVID-19.
An Assessment on Impact of COVID-19 Infection in a Gender Specific Manner
Stem Cell Reviews and Reports, 2020
Coronavirus disease 2019 (COVID-19) is caused by novel coronavirus Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first time reported in December 2019 in Wuhan, China and thereafter quickly spread across the globe. Till September 19, 2020, COVID-19 has spread to 216 countries and territories. Severe infection of SARS-CoV-2 cause extreme increase in inflammatory chemokines and cytokines that may lead to multi-organ damage and respiratory failure. Currently, no specific treatment and authorized vaccines are available for its treatment. Renin angiotensin system holds a promising role in human physiological system specifically in regulation of blood pressure and electrolyte and fluid balance. SARS-CoV-2 interacts with Renin angiotensin system by utilizing angiotensin-converting enzyme 2 (ACE2) as a receptor for its cellular entry. This interaction hampers the protective action of ACE2 in the cells and causes injuries to organs due to persistent angiotensin II (Ang-II) level. Patients with certain comorbidities like hypertension, diabetes, and cardiovascular disease are under the high risk of COVID-19 infection and mortality. Moreover, evidence obtained from several reports also suggests higher susceptibility of male patients for COVID-19 mortality and other acute viral infections compared to females. Analysis of severe acute respiratory syndrome coronavirus (SARS) and Middle East respiratory syndrome coronavirus (MERS) epidemiological data also indicate a gender-based preference in disease consequences. The current review addresses the possible mechanisms responsible for higher COVID-19 mortality among male patients. The major underlying aspects that was looked into includes smoking, genetic factors, and the impact of reproductive hormones on immune systems and inflammatory responses. Detailed investigations of this gender disparity could provide insight into the development of patient tailored therapeutic approach which would be helpful in improving the poor outcomes of COVID-19.
The Impact of Systemic Inflammation on Sex-based Bias Following SARS-CoV-2 Infection
European Journal of Clinical and Biomedical Sciences
Background: The unfavorable clinical outcome (higher rates of severity/morbidity/mortality) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a disproportionate bias towards the male sex despite no sexbased difference noted in the risk for the infection. These outcomes have widely been hinged on dysregulated systemic inflammation. Hence, this study was aimed to evaluate the influence of systemic inflammation on sex-based bias in SARS-CoV-2 infection among indigenes of Nigerian Methods: Patients' data with positive real-time polymerase chain reaction (RT-PCR) test for coronavirus disease 2019 (COVID-19), who were admitted/managed at the Eleme treatment center in Port Harcourt, southern Nigeria, were enrolled for this study. All relevant data was acquired from archived case notes, medical review charts, nurses' charts, and laboratory records by trained research assistants using validated data collection templates. All the collated/abstracted data were analyzed/compared between the male and female patients using both descriptive and comparative statistical tools. Results A total of eligible 598 patients were included in the analysis among them 373 (62.4%) and 225 (37.6%) males and females, respectively. The males were much older (43.63±5.93 vs. 41.15±6.09; p<0.036) with higher mean body mass index and body temperature at presentation. Significant differences were observed in terms of the age distribution, occupational, educational, marital, residential status, cigarette smoking, alcohol consumption, body mass index, comorbid, severity, and clinical outcomes between the males and females (<0.05). In addition, the males had significantly higher mean levels of creatinine, C-reactive protein (CRP), Glasgow Prognostic Score (GPS), D-dimer, total WBC, neutrophil counts, composite neutrophil/lymphocyte ratio (NLR) but lower levels of albumin, total protein, isolated platelet count, and isolated lymphocyte count (p<0.05). The males maintained a significant linear relationship with the CRP (β: 0.
Sex differences in immune responses to SARS-CoV-2 that underlie disease outcomes
2020
A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)1-4. However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. By focusing our analysis on patients with mild to moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines and chemokines including IL-8, IL-18, and CCL5, along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age. Importantly, we found that a poor T cell response negativel...