COVID-19 and Sex Differences

Tu, Haitao; Vermunt, Jane; Abeykoon, Jithma P.; Ghamrawi, Ranine; Gunaratne, Madugodaralalage D. S. K.; Jayachandran, Muthuvel; Narang, Kavita; Parashuram, Santosh; Šuvakov, Sonja; Garovic, Vesna D.

doi:10.1016/j.mayocp.2020.07.024

Cited by 245 publications

(168 citation statements)

References 168 publications

(189 reference statements)

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“…We found that risk of fatal or critical care unit-treated COVID-19 in diabetes rose steeply with age and was higher in males, as has been reported in many other populations. 28 More than a third of people with diabetes who developed fatal or critical care unit-treated COVID-19 lived in residential care homes, emphasising the crucial importance of protecting such vulnerable individuals during the remainder of this pandemic. There was a strong socioeconomic gradient.…”

Section: Discussionmentioning

confidence: 99%

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland

McGurnaghan

Weir

Bishop

et al. 2021

The Lancet Diabetes & Endocrinology

288

258

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Background We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a crossvalidated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. MethodsIn this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. Findings Of the total Scottish population onMarch 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5•8%), 1082 (0•3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89•8%) were aged 60 years or older. In the population without diabetes, 4081 (0•1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1•395 (95% CI 1•304-1•494; p<0•0001, compared with the risk in those without diabetes. The OR was 2•396 (1•815-3•163; p<0•0001) in type 1 diabetes and 1•369 (1•276-1•468; p<0•0001) in type 2 diabetes. Among people with diabetes, adjusted for age, sex, and diabetes duration and type, those who developed fatal or critical care unit-treated COVID-19 were more likely to be male, live in residential care or a more deprived area, have a COVID-19 risk condition, retinopathy, reduced renal function, or worse glycaemic control, have had a diabetic ketoacidosis or hypoglycaemia hospitalisation in the past 5 years, be on more...

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Section: Discussionmentioning

confidence: 99%

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland

McGurnaghan

Weir

Bishop

et al. 2021

The Lancet Diabetes & Endocrinology

288

258

View full text Add to dashboard Cite

show abstract

“…Another study by Haitao et al on the mechanisms by which biological sex can influence the prognosis of COVID-19 disease concluded that the greater severity and mortality in men compared to women is most likely due to a combination of factors: on the one hand, differences regarding behavior and lifestyles and, on the other hand, comorbidities that affect men to a greater extent. They conclude that biological sex differences could affect the risk of contracting the disease, its physiopathogenic mechanisms, and its severity due to, among other causes, the fact that men are more likely to develop the dreaded cytokine storm associated with a higher lethality of the virus [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study

Josa-Laorden

Vieitez

Andreu

et al. 2021

JCM

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There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered.

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“…chromosomes, sex steroids) or gender aspects (e.g. social behavior) 8 . Sex differences of genetic origin are constant throughout life, while sex differences originating from hormonal effects may alter with increasing age.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 induced CYP19A1 expression in the lung correlates with increased aromatization of testosterone-to-estradiol in male golden hamsters

Stanelle-Bertram

Schaumburg

Kouassi

et al. 2020

Preprint

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SARS-CoV-2 infection is associated with increased morbidities in men compared to women. Androgens are believed to play an important role in SARS-CoV-2 pathogenesis in men due to the postulated androgen-dependency of ACE2 and TMPRSS2. However, it is yet unclear whether the sex bias is mediated by SARS-CoV-2 infection itself or by other confounding factors. Here, using the golden hamster model, we show that SARS-CoV-2 infection attacks reproductive organs, causes massive dysregulation of sex hormones and induces elevated transcription of the androgen-to-estrogen converting enzyme aromatase CYP19A1 in the lung. In male hamsters, SARS-CoV-2 infection causes severely depleted testosterone and highly elevated estradiol levels. In female hamsters, SARS-CoV-2 infection causes reduced estradiol levels. Hormonal dysregulation in infected animals is followed by severe weight loss compared to control groups treated with poly(I:C) or PBS. Lungs of SARS-CoV-2 infected animals present abundant CYP19A1 expression in the endothelium and in macrophages, particularly in males. Prominent CYP19A1 expression in endothelial cells and macrophages was verified in lung sections of deceased Covid-19 males compared to females. Our results demonstrate that SARS-CoV-2 infection leads to massive dysregulation of sex hormones, which may increase the risk for sex-specific disease outcome particularly in combination with comorbidities. These findings provide insights into the complex metabolic cross talk between SARS-CoV-2 infection and sex hormones.

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COVID-19 and Sex Differences

Cited by 245 publications

References 168 publications

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study

SARS-CoV-2 induced CYP19A1 expression in the lung correlates with increased aromatization of testosterone-to-estradiol in male golden hamsters

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