ObjectiveWe aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death.DesignSystematic review and meta-analysis.Data sourcesPubMed and Embase through 4 May 2020.Study selectionWe considered cohort and case–control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death.Data extraction and synthesisWe screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale.ResultsWe screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years.ConclusionsMeta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death.PROSPERO registration numberCRD42020180085.

To cite this article: Roach REJ, Cannegieter SC, Lijfering WM. Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment. J Thromb Haemost 2014; 12: 1593-600.Summary. Men have a higher risk of first and recurrent venous thrombosis than do women. However, the pathophysiology underlying this phenomenon is as yet unknown. In this review article, we assessed the prevalence and strength of genetic and acquired risk factors for venous thrombosis for men and women separately, because it is likely that either a difference in effect or distribution of a risk factor explains the risk difference between the sexes. We also summarized the sex-specific results of previous studies on the risk of first and recurrent venous thrombosis. Few explanations for the sex difference were found. The major factor, explaining about 20% difference in population-attributable fraction, was body height. No difference in prevalence or strength for other venous thrombosis risk factors was observed, such as plaster cast immobilization, hospitalization, surgery, trauma, malignancy, hyperhomocysteinemia, factor V Leiden, prothrombin G20210A, or blood group non-O. Alternative explanations for the sex difference are hypothesized in this review, including X-or Y-linked mutations or a mutation on a gene with a sex-specific effect. Future studies should focus on the sex-specific risk of venous thrombosis to unravel the pathophysiology and thereby improve sex-specific treatment and prevention strategies. Even so, male sex can be used as a tool through which individuals at increased risk of first or recurrent venous thrombosis may be identified.

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To cite this article: Venemans-Jellema A, Schreijer AJM, le Cessie S, Emmerich J, Rosendaal FR, Cannegieter SC. No effect of isolated longterm supine immobilization or profound prolonged hypoxia on blood coagulation. J Thromb Haemost 2014; 12: 902-9.Summary. Background: Long-distance air travel is associated with an increased risk of venous thrombosis. The most obvious factor that can explain air travel-related thrombosis is prolonged seated immobilization. In addition, hypobaric hypoxia has been shown to affect coagulation, and the lowered atmospheric pressures present in the cabin during the flight may therefore play an etiologic role. Because immobilization and hypoxic conditions are usually present simultaneously in airplanes or hypobaric chambers, their separate effects on the coagulation system or on thrombosis risk have not been studied extensively. Objectives: To investigate the separate effects of long-term immobilization and profound prolonged hypoxia on blood coagulation. Patients and Methods: We performed two studies in collaboration with European Space Agency/European Space Research and Technology Centre. In the first study, 24 healthy, non-smoking, adult women underwent 60 days of À6°head-down bed rest. In the second study, we took blood samples from 25 healthy men who participated during their stay in the Concordia station in Antarctica, where, due to the atmospheric conditions, continuous severe hypobaric hypoxia is present. In both studies, we measured markers of blood coagulation at baseline and at several time points during the exposures. Results and Conclusions: We observed no increase in coagulation markers during immobilization or in the hypobaric environment, compared with baseline measurements. Our results indicate that neither immobilization nor hypoxia per se affects blood coagulation. These results implicate that a combination of risk factors is necessary to induce the coagulation system during air travel.

Summary. Background: Airline pilots may be at increased risk of venous thromboembolism (VTE) because air travel has recently been established as a risk factor for VTE. Objectives: The aim of this study was to assess the risk of VTE in a cohort of Dutch airline pilots. Patients/Methods: Airline pilots who had been active members of the Dutch aviation society (VNV) were questioned for the occurrence of VTE, presence of risk factors for VTE and number of flight hours per year and rank. Incidence rates among pilots were compared with those of the general Dutch population and with a population of frequently flying employees of multinational organizations. Results and Conclusions: A total of 2630 male pilots were followed-up for a total of 20420 person-years (py). Six venous thromboses were reported, yielding an incidence rate of 0.3 per 1000 py. The standardized morbidity ratio, comparing these pilots with the general Dutch population adjusted for age, was 0.8. Compared with the international employee cohort, the standardized morbidity ratio was 0.7 when all employees were included and 0.6 when only the frequently travelling employees were included. The incidence rate did not increase with number of flight hours per year and did not clearly vary by rank. We conclude that the risk of VTE is not increased amongst airline pilots.