Are sex hormones promising candidates to explain sex disparities in the COVID-19 pandemic?

Brandi, Maria Luisa

doi:10.1007/s11154-021-09692-8

Cited by 30 publications

(32 citation statements)

References 135 publications

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“…Similar to other studies, we found age ( 21 ), male gender ( 28 ), and underlying chronically illness ( 29 ) were risk factors of in-hospital mortality of patients with COVID-19. Our study also found that D-dimer, representing thrombotic risk ( 30 ), and LDH, representing systemic inflammation ( 31 ), were also associated with prognosis in multivariable logistic regression analysis.…”

Section: Discussionsupporting

confidence: 89%

Relationship Between Platelet Count and In-hospital Mortality in Adult Patients With COVID-19: A Retrospective Cohort Study

et al. 2022

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BackgroundThe coronavirus disease 2019 (COVID-19) has become a global pandemic. Systemic inflammation in COVID-19 patients has been associated with poor clinical outcome. This study aims to determine the relationship between platelet count and in-hospital mortality.MethodsThe original data of this study were from article development and validation of a predictive model of in-hospital mortality in COVID-19 patients. In this secondary analysis, we adopted multi-variable logistic regression analyses and smooth curve fitting to assess the independent association between platelet count and in-hospital mortality. We further applied a two-piecewise linear regression model to examine the nonlinear association between platelet count and in-hospital mortality.ResultsOf the 2006 patients, the average age of the participants was 65.9 ± 16.5 years and 42.6% were women. We observed a U-shaped relationship between platelet count and in-hospital mortality. We found two different slopes, the correlations between platelet count and in-hospital mortality of COVID-19 patients were totally different below and above the inflection point which was around 370 × 109/L. On the left side of the inflection point, the OR was 0.996 (OR: 0.996, 95%CI: 0.994–0.998, p < 0.001). On the right side of the inflection point, the OR was 1.011 (OR: 1.011, 95%CI: 1.001–1.021, p = 0.029).ConclusionsA U-shaped association between platelet count and in-hospital mortality was found in the patients with COVID-19. The optimal of platelet count associated with the lowest risk of in-hospital mortality was around 370 × 109/L.

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Section: Discussionsupporting

confidence: 89%

Relationship Between Platelet Count and In-hospital Mortality in Adult Patients With COVID-19: A Retrospective Cohort Study

et al. 2022

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“…Analogously to CAP, the difference between men and women can partially be explained by gender-related factors. Male sex tends to have lifestyle habits which increase risk (e.g., smoking [ 111 ], alcohol, and drugs abuse) and also a higher burden of comorbidities (especially T2DM, COPD, hypertension, cardiovascular diseases, and chronic kidney disease) [ 111 ]; men were also found to wash their hand less frequently than women [ 112 ] and, after retirement, spend more time in public places than women, who are, conversely, prone to living alone and experiencing social isolation [ 113 ].…”

Section: Covid-19 Pneumoniamentioning

confidence: 99%

Sex and gender differences in community-acquired pneumonia

et al. 2022

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Awareness of the influence of sex ands gender on the natural history of several diseases is increasing. Community-acquired pneumonia (CAP) is the most common acute respiratory disease, and it is associated with both morbidity and mortality across all age groups. Although a role for sex- and gender-based differences in the development and associated complications of CAP has been postulated, there is currently high uncertainty on the actual contribution of these factors in the epidemiology and clinical course of CAP. More evidence has been produced on the topic during the last decades, and sex- and gender-based differences have also been extensively studied in COVID-19 patients since the beginning of the SARS-CoV-2 pandemic. This review aims to provide an extensive outlook of the role of sex and gender in the epidemiology, pathogenesis, treatment, and outcomes of patients with CAP, and on the future research scenarios, with also a specific focus on COVID-19.

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“…At the same time, the ratio of male vs. female mortality is 1.51, as 60.2% of deaths include men, and 39.8% are in female patients. So far, there is no single explanation for this disparity; most probably, several reasons are behind this statistic, observed in all countries and continents included in the analysis with the exception of Pakistan and Australia [ 12 , 14 ]. Not one but a combination of several reasons is considered to be a possible explanation for sex-dependent Covid-19 susceptibility.…”

Section: Introductionmentioning

confidence: 99%

“…Not one but a combination of several reasons is considered to be a possible explanation for sex-dependent Covid-19 susceptibility. Among them, lifestyle habits, time until medical care initiation, the prevalence of comorbidities, smoking habits, sex-dependent differences in immune system responsiveness and expression of genes related to Covid-19 progression very likely contribute to a less effective response to Covid-19 challenge in males compared to females [ 12 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Effect of 17β-estradiol on the daily pattern of ACE2, ADAM17, TMPRSS2 and estradiol receptor transcription in the lungs and colon of male rats

Herichová

Jendrisková²,

Pidíková³

et al. 2022

PLoS ONE

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Covid-19 progression shows sex-dependent features. It is hypothesized that a better Covid-19 survival rate in females can be attributed to the presence of higher 17β-estradiol (E2) levels in women than in men. Virus SARS-CoV-2 is enabled to enter the cell with the use of angiotensin converting enzyme 2 (ACE2). The expression of several renin-angiotensin system components has been shown to exert a rhythmic pattern, and a role of the circadian system in their regulation has been implicated. Therefore, the aim of the study is to elucidate possible interference between E2 signalling and the circadian system in the regulation of the expression of ACE2 mRNA and functionally related molecules. E2 was administered at a dosage of 40 μg/kg/day for 7 days to male Wistar rats, and sampling of the lungs and colon was performed during a 24-h cycle. The daily pattern of expression of molecules facilitating SARS-CoV-2 entry into the cell, clock genes and E2 receptors was analysed. As a consequence of E2 administration, a rhythm in ACE2 and TMPRSS2 mRNA expression was observed in the lungs but not in the colon. ADAM17 mRNA expression showed a pronounced rhythmic pattern in both tissues that was not influenced by E2 treatment. ESR1 mRNA expression exerted a rhythmic pattern, which was diminished by E2 treatment. The influence of E2 administration on ESR2 and GPER1 mRNA expression was greater in the lungs than in the colon as a significant rhythm in ESR2 and GPER1 mRNA expression appeared only in the lungs after E2 treatment. E2 administration also increased the amplitude of bmal1 expression in the lungs, which implicates altered functioning of peripheral oscillators in response to E2 treatment. The daily pattern of components of the SARS-CoV-2 entrance pathway and their responsiveness to E2 should be considered in the timing of pharmacological therapy for Covid-19.

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Are sex hormones promising candidates to explain sex disparities in the COVID-19 pandemic?

Cited by 30 publications

References 135 publications

Relationship Between Platelet Count and In-hospital Mortality in Adult Patients With COVID-19: A Retrospective Cohort Study

Relationship Between Platelet Count and In-hospital Mortality in Adult Patients With COVID-19: A Retrospective Cohort Study

Sex and gender differences in community-acquired pneumonia

Effect of 17β-estradiol on the daily pattern of ACE2, ADAM17, TMPRSS2 and estradiol receptor transcription in the lungs and colon of male rats

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