Sex and gender differences in COVID-19: More to be learned!

Ya’qoub, Lina; Elgendy, Islam Y.; Pepine, Carl J.

doi:10.1016/j.ahjo.2021.100011

Cited by 54 publications

(74 citation statements)

References 30 publications

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“…In this sense, the double copy of the X chromosome in females is essential against viral infections. However, it is observed that female are at a higher risk of COVID-19 clinical manifestations in the long term than males [43].…”

Section: Discussionmentioning

confidence: 97%

A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death

Gutiérrez-Abejón

Herrera‐Gómez

Martín-García

et al. 2021

JCDD

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A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

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Section: Discussionmentioning

confidence: 97%

A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death

Gutiérrez-Abejón

Herrera‐Gómez

Martín-García

et al. 2021

JCDD

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“…Sex and gender strongly influence the severity and mortality of the disease, which hare higher in men than in women across the lifespan [ 41 , 42 , 43 ]. COVID-19 is more devastating in old men [ 53 ], who have a higher risk for intensive care unit admissions and mechanical ventilation [ 65 ]. Further, men die twice as much compared with women [ 65 ].…”

Section: Sex and Gender Aspects In Covid-19mentioning

confidence: 99%

“…COVID-19 is more devastating in old men [ 53 ], who have a higher risk for intensive care unit admissions and mechanical ventilation [ 65 ]. Further, men die twice as much compared with women [ 65 ]. The higher rates of mortality or severity in men are still present after adjusting for comorbidities.…”

Section: Sex and Gender Aspects In Covid-19mentioning

confidence: 99%

“…Sex differences in immunological and inflammatory diseases persist across all lifespans [ 38 ], with the aging of the immune system more pronounced in men than in women [ 39 ]. Besides, these differences can be gender-dependent because they involve the social role, lifestyles such as smoking, which is a risk factor, identity, and relations, which play a role, for example, in exposure [ 65 ]. Men tend to have habits that could be conducive to viral transmission [ 67 ].…”

Section: Sex and Gender Aspects In Covid-19mentioning

confidence: 99%

“…Generally, women are less enrolled in clinical trials, although with some exceptions [ 17 ]; in COVID-19 trials, women only represented ~1/3 of subjects [ 65 ]. The under-representation of women has been observed both in randomized clinical trials and in some observational studies [ 65 ]. The under-enrollment of women for some authors depends on the lower severity of COVID-19 in women [ 72 ].…”

Section: Sex and Gender Aspects In Drug Response In Covid-19mentioning

confidence: 99%

See 2 more Smart Citations

Just a Reflection: Does Drug Repurposing Perpetuate Sex-Gender Bias in the Safety Profile?

Campesi

Racagni

Franconi³

2021

Pharmaceuticals

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Vaccines constitute a strategy to reduce the burden of COVID-19, but the treatment of COVID-19 is still a challenge. The lack of approved drugs for severe COVID-19 makes repurposing or repositioning of approved drugs a relevant approach because it occurs at lower costs and in a shorter time. Most preclinical and clinical tests, including safety and pharmacokinetic profiles, were already performed. However, infective and inflammatory diseases such as COVID-19 are linked with hypoalbuminemia and downregulation of both phase I and phase II drug-metabolizing enzymes and transporters, which can occur in modifications of pharmacokinetics and consequentially of safety profiles. This appears to occur in a sex- and gender-specific way because of the sex and gender differences present in the immune system and inflammation, which, in turn, reflect on pharmacokinetic parameters. Therefore, to make better decisions about drug dosage regimens and to increases the safety profile in patients suffering from infective and inflammatory diseases such as COVID-19, it is urgently needed to study repurposing or repositioning drugs in men and in women paying attention to pharmacokinetics, especially for those drugs that are previously scarcely evaluated in women.

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Exploratory analysis of interleukin‐38 in hospitalized COVID‐19 patients

Graaf

Teufel

Nooijer

et al. 2022

Immunity Inflam & Disease

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Introduction A major contributor to coronavirus disease 2019 (COVID‐19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin‐38 (IL−38) is an IL‐1 family member with broad anti‐inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL‐38 in COVID‐19 patients in comparison to healthy controls, whereas two other studies report no differences in IL‐38 concentrations. Methods Here, we present an exploratory, retrospective cohort study of circulating IL‐38 concentrations in hospitalized COVID‐19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age‐ and sex‐matched healthy subjects. Plasma IL‐38 concentrations were measured by enzyme‐linked immunosorbent assay, disease‐related proteins by proximity extension assay, and clinical data were retrieved from hospital records. Results IL‐38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL‐38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL‐38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL‐38 and the inflammatory biomarker d‐dimer was observed in men of the validation cohort. In women of the validation cohort, IL‐38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL‐38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL‐10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein. Conclusions These data indicate that IL‐38 is not associated with disease outcomes in hospitalized COVID‐19 patients. However, moderate correlations between IL‐38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL‐38 concentrations are not indicative of COVID‐19 severity, its anti‐inflammatory effects may reduce COVID‐19 severity and should be experimentally investigated.

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Sex and gender differences in COVID-19: More to be learned!

Cited by 54 publications

References 30 publications

A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death

A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death

Just a Reflection: Does Drug Repurposing Perpetuate Sex-Gender Bias in the Safety Profile?

Exploratory analysis of interleukin‐38 in hospitalized COVID‐19 patients

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