Sex differences in viral entry protein expression and host transcript responses to SARS-CoV-2.

Epidemiological studies suggest that men exhibit a higher mortality rate to COVID-19 than women, yet the underlying biology is largely unknown. Here, we seek to delineate sex differences in the gene expression of viral entry proteins ACE2 and TMPRSS2, and host transcriptional responses to SARS-CoV-2 through large-scale analysis of genomic and clinical data. We first compiled 220,000 human gene expression profiles from three databases and completed the meta-information through machine learning and manual annotation.

Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets.

Background: Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. "CKD Patch" is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures.

Methods: Utilizing data from 4,143,535 adults from 35 datasets, we developed several "CKD Patches" incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE).

SGLT2 Inhibitors: Emerging Roles in the Protection Against Cardiovascular and Kidney Disease Among Diabetic Patients.

Purpose Of Review: Type 2 diabetes mellitus (T2DM) is a prevalent disease with the severe clinical implications including myocardial infarction, stroke, and kidney disease. Therapies focusing on glycemic control in T2DM such as biguanides, sulfonylureas, thiazolidinediones, and insulin-based regimens have largely failed to substantially improve cardiovascular and kidney outcomes. We review the recent findings on sodium-glucose co-transporter type 2 (SGLT2) inhibitors which have shown to have beneficial cardiovascular and kidney-related effects.

Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: a cross-sectional study.

Objective: Multiple clinical trials fail to identify clinically measurable health benefits of daily multivitamin and multimineral (MVM) consumption in the general adult population. Understanding the determinants of widespread use of MVMs may guide efforts to better educate the public about effective nutritional practices. The objective of this study was to compare self-reported and clinically measurable health outcomes among MVM users and non-users in a large, nationally representative adult civilian non-institutionalised population in the USA surveyed on the use of complementary health practices.

Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19.

Background: Patients with pre-existing heart failure (HF) are likely at higher risk for adverse outcomes in coronavirus disease-2019 (COVID-19), but data on this population are sparse.

Objectives: This study described the clinical profile and associated outcomes among patients with HF hospitalized with COVID-19.

Methods: This study conducted a retrospective analysis of 6,439 patients admitted for COVID-19 at 1 of 5 Mount Sinai Health System hospitals in New York City between February 27 and June 26, 2020.

Hospitalised COVID-19 patients of the Mount Sinai Health System: a retrospective observational study using the electronic medical records.

Objective: To assess association of clinical features on COVID-19 patient outcomes.

Design: Retrospective observational study using electronic medical record data.

Setting: Five member hospitals from the Mount Sinai Health System in New York City (NYC).

Utilization of Deep Learning for Subphenotype Identification in Sepsis-Associated Acute Kidney Injury.

Background And Objectives: Sepsis-associated AKI is a heterogeneous clinical entity. We aimed to agnostically identify sepsis-associated AKI subphenotypes using deep learning on routinely collected data in electronic health records.

Design, Setting, Participants, & Measurements: We used the Medical Information Mart for Intensive Care III database, which consists of electronic health record data from intensive care units in a tertiary care hospital in the United States.

Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program.

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability.

Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls.

Gastrointestinal involvement attenuates COVID-19 severity and mortality.

Unlabelled: Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of coronavirus disease 2019 (COVID-19), we investigated intestinal infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its effect on disease pathogenesis. SARS-CoV-2 was detected in small intestinal enterocytes by immunofluorescence staining or electron microscopy, in 13 of 15 patients studied. High dimensional analyses of GI tissues revealed low levels of inflammation in general, including active downregulation of key inflammatory genes such as and and reduced frequencies of proinflammatory dendritic cell subsets.

Tissue-specific genetic features inform prediction of drug side effects in clinical trials.

Adverse side effects often account for the failure of drug clinical trials. We evaluated whether a phenome-wide association study (PheWAS) of 1167 phenotypes in >360,000 U.K.

Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition.

The Polygenic and Monogenic Basis of Blood Traits and Diseases.

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics.

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro.

AKI in Hospitalized Patients with COVID-19.

Background: Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described.

Methods: This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020.

Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19.

Background: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings.

Objectives: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies.

Sex Differences in Age and Comorbidities for COVID-19 Mortality in Urban New York City.

Previous studies demonstrated a higher COVID-19 fatality rate in men. The aim of this study was to compare age and comorbidities between women and men who died from COVID-19. We retrospectively analyzed data of COVID-19 patients hospitalized to a large academic hospital system in New York City between March 1 and May 9, 2020.

Author Correction: Sampling the host response to SARS-CoV-2 in hospitals under siege.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Federated Learning of Electronic Health Records Improves Mortality Prediction in Patients Hospitalized with COVID-19.

Machine learning (ML) models require large datasets which may be siloed across different healthcare institutions. Using federated learning, a ML technique that avoids locally aggregating raw clinical data across multiple institutions, we predict mortality within seven days in hospitalized COVID-19 patients. Patient data was collected from Electronic Health Records (EHRs) from five hospitals within the Mount Sinai Health System (MSHS).