Reply to Jakovac: Sex differences in COVID-19 course and outcome: progesterone should not be neglected.
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ABSTRACT:
SUBMITTER: Gargaglioni LH
PROVIDER: S-EPMC7607497 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Reply to Jakovac: Sex differences in COVID-19 course and outcome: progesterone should not be neglected.
Gargaglioni Luciane H LH Marques Danuzia A DA
Journal of applied physiology (Bethesda, Md. : 1985) 20201101 5
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Project description: Not available
| S-EPMC6999112 | biostudies-literature
Project description:Background: Smaller studies suggest lower morbidity and mortality associated with coronavirus disease 2019 (COVID-19) in women. Our aim is to assess the impact of female sex on outcomes in a large cohort of patients hospitalized with COVID-19. Materials and Methods: This is a retrospective observational cohort study of 10,630 adult patients hospitalized with a confirmed COVID-19 polymerase chain reaction between March 1, 2020 and April 27, 2020, with follow-up conducted through June 4, 2020. Logistic regression was used to examine the relationship between sex and the primary outcomes, including length of stay, admission to intensive care unit (ICU), need for mechanical ventilation, pressor requirement, and all-cause mortality as well as major adverse events and in-hospital COVID-19 treatments. Results: In the multivariable analysis, women had 27% lower odds of in-hospital mortality (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.66-0.81; p < 0.001), 24% lower odds of ICU admission (OR = 0.76, 95% CI 0.69-0.84; p < 0.001), 26% lower odds of mechanical ventilation (OR = 0.74, 95% CI 0.66-0.82; p < 0.001), and 25% lower odds of vasopressor requirement (OR = 0.75, 95% CI 0.67-0.84; p < 0.001). Women had 34% less odds of having acute cardiac injury (OR = 0.66, 95% CI 0.59-0.74; p < 0.001; n = 7,289), 16% less odds of acute kidney injury (OR = 0.84, 95% CI 0.76-0.92; p < 0.001; n = 9,840), and 27% less odds of venous thromboembolism (OR = 0.73, 95% CI 0.56-0.96; p < 0.02; c-statistic 0.85, n = 9,407). Conclusions: Female sex is associated with lower odds of in-hospital outcomes, major adverse events, and all-cause mortality. There may be protective mechanisms inherent to female sex, which explain differences in COVID-19 outcomes.
| S-EPMC8182657 | biostudies-literature
Project description:Many countries have been affected by the worldwide outbreak of COVID-19. Among Western countries, Italy has been particularly hit at the beginning of the pandemic, immediately after China. In Italy and elsewhere, women seem to be less affected than men by severe/fatal COVID-19 infection, regardless of their age. Although women and men are affected differently by this infection, very few studies consider different therapeutic approaches for the two sexes. Understanding the mechanisms underlying these differences may help to find appropriate and sex specific therapies. Here, we consider that other mechanisms are involved to explain this difference, in addition to the protection attributable to oestrogens. Several X-linked genes (such as ACE2) and Y-linked genes (SRY and SOX9) may explain sex differences. Cardiovascular comorbidities are among the major enhancers of virus lethality. In addition, the number of sex-independent, non-genetic factors that can change susceptibility and mortality is enormous, and many other factors should be considered, including gender and cultural habits in different countries.
| S-EPMC7405496 | biostudies-literature
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:COVID-19 infection affects different organs of the human body, and blood cells are not an exception. Peripheral blood smear (PBS) is a simple and available method to investigate blood cells' morphologic changes. In this study, we aimed to determine the morphologic changes and abnormalities of COVID-19 patients and their relation to the patients' clinical course. In this prospective cross-sectional study, we included 89 PCR-positive COVID-19 patients. A pathologist examined the PBS findings of these patients. The patients' clinical course, including severity, outcome, intubation, and ICU admission, was extracted from their profiles. The statistical analyses were done to find out the relation between PBS findings and patients' clinical course. Results showed that smudge cells are the most frequent abnormality in our participants. Other findings were schistocyte; atypical lymphocytes; and increased large granular lymphocytes, shift to left of granulocytes, giant platelets, and leukoerythroblastic reaction. Our results did not show any statistically significant relationship between PBS findings and their clinical course. Although other studies suggested PBS as a possible predictive tool for COVID-19 disease, our study showed that these findings could not predict nor relate to the patients' clinical course.Supplementary informationThe online version contains supplementary material available at 10.1007/s12308-021-00459-3.
| S-EPMC8255335 | biostudies-literature
Project description:BackgroundCOVID-19 causes high morbidity and mortality in adult lung transplant (LTX) recipients. Data on COVID-19 in children after LTX is limited. We report the clinical presentation and outcome of SARS-CoV-2 infection in 19 pediatric LTX recipients.MethodsBetween March 2020 and June 2022, SARS-CoV-2 testing was performed on all pediatric LTX patients with COVID-19 symptoms or contact with a SARS-CoV-2 infected person. Positive patients were prospectively evaluated for symptoms, treatment and outcome. Vaccination status and immune response were recorded.ResultsNineteen out of 51 pediatric LTX recipients had a SARS-CoV-2 infection. Mean age was 12.3 years (IQR 9-17), 68% were female, 84% had preexisting comorbidities. Mean time between LTX and SARS-CoV-2 infection was 4.8 years (IQR 2-6). No patients experienced severe COVID-19: 11% were asymptomatic, and 89% had mild symptoms, primarily rhinitis (74%), fever (47%), and cough (37%). One SARS-CoV-2 positive patient was hospitalized due to combined fungal and bacterial infection. Mean duration of symptoms was 10.5 days (IQR 3-16), whereas mean period of positivity by antigen test was 21 days (IQR 9-27, p = 0.013). Preventive antiviral therapy was initiated in 3 patients. After a mean follow-up of 2.5 months (IQR 1.1-2.4), no patient reported persistent complaints related to COVID-19. Lung function tests remained stable.ConclusionsUnlike adult LTX recipients, children and adolescents are at low risk for severe COVID-19, even with risk factors beyond immunosuppression. Our findings cast doubt on the necessity of excessive isolation for these patients and should reassure clinicians and caregivers of LTX patients.
| S-EPMC9719846 | biostudies-literature
Project description:Although some studies reported the comprehensive mRNA expression analysis of coronavirus disease 2019 (COVID-19) using blood samples to understand its pathogenesis, the characteristics of RNA expression in COVID-19 and sepsis have not been compared. We compared the transcriptome expression of whole blood samples from patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with sepsis caused by other bacteria who entered the intensive care unit to clarify the COVID-19-specific RNA expression and understand its pathogenesis. Transcriptomes related to mitochondria were upregulated in COVID-19, whereas those related to neutrophils were upregulated in sepsis. However, the transcriptomes related to neutrophils were upregulated in both COVID-19 and sepsis compared to in healthy controls, whereas the mitochondrial transcriptomes were upregulated in COVID-19 and downregulated in sepsis compared to in healthy controls. Moreover, sepsis showed sub-optimal intrinsic apoptotic features compared with COVID-19. The transcriptome expression of COVID-19 has been examined in vitro but has not been widely validated using human specimens. This study improves the understanding of the pathogenesis of COVID-19 and can contribute to the development of treatments.
2022-11-29 | GSE199816 | GEO
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:Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
| S-EPMC9652109 | biostudies-literature
Project description:BackgroundMales and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration.MethodsWe performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.ResultsWe found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3-3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients.ConclusionsMales had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.
| S-EPMC8256650 | biostudies-literature