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The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Background: Despite known clinical benefits, guideline-recommended heart rate (HR) control is not achieved for a significant proportion of patients with HF with reduced ejection fraction. The wearable cardioverter-defibrillator (WCD) provides continuous HR monitoring and alerts that could aid medication titration.
Objective: This study sought to evaluate sex differences in achieving guideline-recommended HR control during a period of WCD use.
Methods: Data from patients fitted with a WCD from 2015 to 2018 were obtained from the manufacturer’s database (ZOLL). The proportion of patients with adequate nighttime resting HR control at the beginning of use (BOU) and at the end of use (EOU) were compared by sex. Adequate HR control was defined as having a nighttime median HR <70 beats/min.
Results: A total of 21,440 women and a comparative sample of 17,328 men (median 90 [IQR 59–116] days of WCD wear) were included in the final dataset. Among patients who did not receive a shock, over half had insufficient HR control at BOU (59% of women, 53% of men). Although the proportion of patients with resting HR ≥70 beats/min improved by EOU, 43% of women and 36% of men did not achieve guideline-recommended HR control.
Conclusion: A significant proportion of women and men did not achieve adequate HR control during a period of medical therapy optimization. Compared with men, a greater proportion of women receiving WCD shocks had insufficiently controlled HR in the week preceding ventricular tachyarrhythmia/ventricular fibrillation and 43% of nonshocked women, compared with 36% of men, did not reach adequate HR control during the study period. The WCD can be utilized as a remote monitoring tool to record HR and inform adequate uptitration of beta-blockers, with particular focus on reducing the treatment gap in women.