Helping patients discuss CINV management : development of a patient charter

In April 2012, an Expert Group of specialist cancer nurses working in a variety of settings (e.g. chemotherapy delivery, chemotherapy service design, research, nurse leadership and patient information/advocacy) participated in telephone/web-based meetings, with the aim of sharing current experience of chemotherapy-induced nausea and vomiting (CINV) management, and reaching a consensus on the development of a Patient Charter, designed to help patients understand CINV management, and setting out key questions they may wish to ask their healthcare professionals

Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol

COVID-19; Cardiologia; PronòsticCOVID-19; Cardiología; PronósticoCOVID 19; Cardiology; PrognosisBackground Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. Study and design This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. Conclusion The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.SB. Research grant (COV20/00040) from the Carlos III Institute, Madrid, Spain

Economic impact of the first pass effect in mechanical thrombectomy for acute ischaemic stroke treatment in Spain: a cost-effectiveness analysis from the national health system perspective

Health economics; Neuroradiology; StrokeEconomia de la salut; Neuroradiologia; IctusEconomía de la Salud; Neurorradiología; IctusObjective The mechanical thrombectomy (MT) benefit is related to the degree of reperfusion achieved. First pass effect (FPE) is defined as complete/near revascularisation of the large-vessel occlusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) after a single device pass. This study assessed the health benefit and economic impact of achieving FPE for acute ischaemic stroke (AIS) patients from the Spanish National Health System (NHS) perspective. Design A lifetime Markov model was used to estimate incremental costs and health outcomes (measured in quality-adjusted life-years (QALYs)) of patients that achieve FPE. A subanalysis of the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischaemic Stroke (STRATIS) registry was performed to obtain clinical outcomes. The base case included all patients that achieved at least a final mTICI ≥2 b, while the alternative scenario included all patients regardless of their final mTICI (0–3). Treatment costs were updated to reflect current practice based on expert panel consensus, while other acute and long-term costs were obtained from a previous cost-effectiveness analysis of MT performed in Spain. Sensitivity analyses were performed to assess the model’s robustness. Setting Spanish healthcare perspective. Participants AIS patients in Spain. Interventions FPE following MT. Outcome measures The model estimated QALYs, lifetime costs and net monetary benefit for the FPE and non-FPE group, depending on the inclusion of reperfusion groups and formal care costs. Results STRATIS subanalysis estimated significantly better clinical outcomes at 90 days for the FPE group in all scenarios. In the base case, the model estimated lifetime cost saving per patient of €16 583 and an incremental QALY gain of 1.2 years of perfect health for the FPE group. Cost savings and QALY gains were greater in the alternative scenario (-€44 289; 1.75). In all scenarios, cost savings were driven by the long-term cost reduction. Conclusion Achieving FPE after MT can lead to better health outcomes per AIS patient and important cost savings for the Spanish NHS.This study was sponsored by Medtronic

Development of an updated, standardized, patient-centered outcome set for lung cancer

BACKGROUND: In 2016, the International Consortium for Health Outcomes Measurement (ICHOM) defined an international consensus recommendation of the most important outcomes for lung cancer patients. The European Health Outcomes Observatory (H2O) initiative aimed to develop an updated patient-centered core outcome set (COS) for lung cancer, to capture the patient perspective of the impact of lung cancer and (novel) treatments using a combination of patient-reported outcome (PRO) instruments and clinical data as a means to drive value-based health-care. MATERIAL AND METHODS: An international, expert team of patient representatives, multidisciplinary healthcare professionals, academic researchers and pharmaceutical industry representatives (n = 17) reviewed potential outcomes generated through literature review. A broader group of patients/patient representatives (n = 31), healthcare professionals / academic researchers (n = 83), pharmaceutical industry representatives (n = 26), and health authority representatives (n = 6) participated in a Delphi study. In two survey rounds, participants scored the relevance of outcomes from a preliminary list. The threshold for consensus was defined as ≥ 70 % of participants scoring an outcome as 'highly relevant'. In concluding consensus-meeting rounds, the expert multidisciplinary team finalized the COS. RESULTS: The preliminary list defined by the core group consisted of 102 outcomes and was prioritized in the Delphi procedure to 64. The final lung cancer COS includes: 1) case-mix factors (n = 27); 2) PROs related to health-related quality of life (HRQoL) (n = 25); 3) clinical outcomes (n = 12). Patient-reported symptoms beyond domains included in the ICHOM lung cancer set in 2016 were insomnia, nausea, vomiting, anxiety, depression, lack of appetite, gastric problems, constipation, diarrhoea, dysphagia, and haemoptysis. CONCLUSIONS: We will implement the lung cancer COS in Europe within the H2O initiative by collecting the outcomes through a combination of clinician-reported measures and PRO measures. The COS will support the adoption and reporting of lung cancer measures in a standardized way across Europe and empower patients with lung cancer to better manage their health care

Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol

Background: Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. Study and design: This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. Conclusion: The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19

Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina

PurposeThe aim of this study was to investigate, the neuroprotective effects of a new Gramine derivative named: ITH12657, in a model of retinal excitotoxicity induced by intravitreal injection of NMDA.MethodsAdult Sprague Dawley rats received an intravitreal injection of 100 mM NMDA in their left eye and were treated daily with subcutaneous injections of ITH12657 or vehicle. The best dose–response, therapeutic window study, and optimal treatment duration of ITH12657 were studied. Based on the best survival of Brn3a + RGCs obtained from the above-mentioned studies, the protective effects of ITH12657 were studied in vivo (retinal thickness and full-field Electroretinography), and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs and their subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs.ResultsAdministration of 10 mg/kg ITH12657, starting 12 h before NMDA injection and dispensed for 3 days, resulted in the best significant protection of Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-treated rats showed significant preservation of retinal thickness and functional protection against NMDA-induced retinal excitotoxicity. Ex vivo results showed that ITH12657 afforded a significant protection against NMDA-induced excitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, but not for the population of αOFF-RGC, while the population of α-ONtRGC was fully resistant to NMDA-induced excitotoxicity.ConclusionSubcutaneous administration of ITH12657 at 10 mg/kg, initiated 12 h before NMDA-induced retinal injury and continued for 3 days, resulted in the best protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-induced RGC death. The population of αOFF-RGCs was extremely sensitive while α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Effect of an Intensive Weight-Loss Lifestyle Intervention on Kidney Function: A Randomized Controlled Trial

Introduction: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. Methods: Randomized controlled "PREvención con DIeta MEDiterránea-Plus"(PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDiet, PA promotion, and behavioral support (intervention) or usual-care advice to adhere to an energy-unrestricted MedDiet (control) between September 2013 and December 2016. The primary outcome was 1-year change in estimated glomerular filtration rate (EGFR). Secondary outcomes were changes in urine albumin-to-creatinine ratio (UACR), incidence of moderately/severely impaired EGFR (<60 mL/min/1.73 m2) and micro-to macroalbuminuria (UACR ≥30 mg/g), and reversion of moderately (45 to <60 mL/min/1.73 m2) to mildly impaired GFR (60 to <90 mL/min/1.73 m2) or micro-to macroalbuminuria. Results: After 1 year, EGFR declined by 0.66 and 1.25 mL/min/1.73 m2 in the intervention and control groups, respectively (mean difference, 0.58 mL/min/1.73 m2; 95% CI: 0.15-1.02). There were no between-group differences in mean UACR or micro-to macroalbuminuria changes. Moderately/severely impaired EGFR incidence and reversion of moderately to mildly impaired GFR were 40% lower (HR 0.60; 0.44-0.82) and 92% higher (HR 1.92; 1.35-2.73), respectively, in the intervention group. Conclusions: The PREDIMED-Plus lifestyle intervention approach may preserve renal function and delay CKD progression in overweight/obese adults.This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is cofunded by the European Regional Development Fund (5 coordinated FIS projects leaded by J.S.-S and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926; PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332); the Especial Action Project entitled Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S.; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to M.Á.M.-G.; the Recercaixa (No. 2013ACUP00194) grant to J.S.-S.; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; funds from the European Regional Development Fund (CB06/03); International Nut & Dried Fruit Council – FESNAD (Long-term effects of an energyrestricted Mediterranean diet on mortality and cardiovascular disease 2014–2015, No. 201302) (PI: M.Á.M.-G.); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (PI: D.R.); grant of support to research groups No. 35/2011 (Balearic Islands Gov.; FEDER funds) (J.A.T. and C.B.); the JR17/00022 (ISCIII) grant to O.C.; the Boosting young talent call grant program for the development of IISPV research projects 2019–2021 (Ref.: 2019/IISPV/03 grant to A.D.-L.); the Societat Catalana d’Endocrinologia i Nutrició (SCEN) Clinical-Research Grant 2019 (IPs: J.S.-S. and A.D.-L.). Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 supported by CIBEROBN entitled Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant to A.D.-L

CALIFA, the Calar Alto Legacy Integral Field Area survey III. Second public data release

CALIFA is the first legacy survey being performed at Calar Alto. The CALIFA collaboration would like to thank the IAA-CSIC and MPIA-MPG as major partners of the observatory, and CAHA itself, for the unique access to telescope time and support in manpower and infrastructures. The CALIFA collaboration thanks also the CAHA staff for the dedication to this project. R.G.B., R.G.D., and E.P. are supported by the Spanish Ministerio de Ciencia e Innovacion under grant AYA2010-15081. S.Z. is supported by the EU Marie Curie Integration Grant "SteMaGE" Nr. PCIG12-GA-2012-326466 (Call Identifier: FP7-PEOPLE-2012 CIG). J.F.B. acknowledges support from grants AYA2010-21322-C03-02 and AIB-2010-DE-00227 from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as from the FP7 Marie Curie Actions of the European Commission, via the Initial Training Network DAGAL under REA grant agreement number 289313. Support for L.G. is provided by the Ministry of Economy, Development, and Tourism's Millennium Science Initiative through grant IC12009, awarded to The Millennium Institute of Astrophysics, M.A.S.L.G. also acknowledges support by CONICYT through FONDECYT grant 3140566. A.G. acknowledges support from the FP7/2007-2013 under grant agreement n. 267251 (AstroFIt). J.M.G. acknowledges support from the Fundacao para a Ciencia e a Tecnologia (FCT) through the Fellowship SFRH/BPD/66958/2009 from FCT (Portugal) and research grant PTDC/FIS-AST/3214/2012. RAM was funded by the Spanish programme of International Campus of Excellence Moncloa (CEI). J.M.A. acknowledges support from the European Research Council Starting Grant (SEDmorph; P.I. V. Wild). I.M., J.M. and A.d.O. acknowledge the support by the projects AYA2010-15196 from the Spanish Ministerio de Ciencia e Innovacion and TIC 114 and PO08-TIC-3531 from Junta de Andalucia. AMI acknowledges support from Agence Nationale de la Recherche through the STILISM project (ANR-12-BS05-0016-02). M.M. acknowledges financial support from AYA2010-21887-C04-02 from the Ministerio de Economia y Competitividad. P.P. is supported by an FCT Investigador 2013 Contract, funded by FCT/MCTES (Portugal) and POPH/FSE (EC). P.P. acknowledges support by FCT under project FCOMP-01-0124-FEDER-029170 (Reference FCT PTDC/FIS-AST/3214/2012), funded by FCT-MEC (PIDDAC) and FEDER (COMPETE). T.R.L. thanks the support of the Spanish Ministerio de Educacion, Cultura y Deporte by means of the FPU fellowship. PSB acknowledges support from the Ramon y Cajal program, grant ATA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO). C.J.W. acknowledges support through the Marie Curie Career Integration Grant 303912. V.W. acknowledges support from the European Research Council Starting Grant (SEDMorph P.I. V. Wild) and European Career Re-integration Grant (Phiz-Ev P.I.V. Wild). Y.A. acknowledges financial support from the Ramon y Cajal programme (RyC-2011-09461) and project AYA2013-47742-C4-3-P, both managed by the Ministerio de Economia y Competitividad, as well as the "Study of Emission-Line Galaxies with Integral-Field Spectroscopy" (SELGIFS) programme, funded by the EU (FP7-PEOPLE-2013-IRSES-612701) within the Marie-Sklodowska-Curie Actions scheme. We thank the referee David Wilman for very useful comments that improved the presentation of the paper.This paper describes the Second Public Data Release (DR2) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. The data for 200 objects are made public, including the 100 galaxies of the First Public Data Release (DR1). Data were obtained with the integral-field spectrograph PMAS/PPak mounted on the 3.5 m telescope at the Calar Alto observatory. Two different spectral setups are available for each galaxy, (i) a lowresolution V500 setup covering the wavelength range 3745–7500 Å with a spectral resolution of 6.0 Å (FWHM); and (ii) a medium-resolution V1200 setup covering the wavelength range 3650–4840 Å with a spectral resolution of 2.3 Å (FWHM). The sample covers a redshift range between 0.005 and 0.03, with a wide range of properties in the color–magnitude diagram, stellar mass, ionization conditions, and morphological types. All the cubes in the data release were reduced with the latest pipeline, which includes improved spectrophotometric calibration, spatial registration, and spatial resolution. The spectrophotometric calibration is better than 6% and the median spatial resolution is 200 : 4. In total, the second data release contains over 1.5 million spectra.Instituto de Salud Carlos III Spanish Government AYA2010-15081 AYA2010-15196European Union (EU) PCIG12-GA-2012-326466Spanish Ministry of Economy and Competitiveness (MINECO) AYA2010-21322-C03-02 AIB-2010-DE-00227FP7 Marie Curie Actions of the European Commission, via the Initial Training Network DAGAL under REA 289313Ministry of Economy, Development, and Tourism's Millennium Science Initiative IC12009Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 3140566Fundacao para a Ciencia e a Tecnologia (FCT) from FCT (Portugal) SFRH/BPD/66958/2009Spanish programme of International Campus of Excellence Moncloa (CEI)European Research Council (ERC)Junta de Andalucia TIC 114 PO08-TIC-3531French National Research Agency (ANR) ANR-12-BS05-0016-02Spanish Government AYA2010-21887-C04-02FCT Investigador Contract - FCT/MCTES (Portugal)European Commission Joint Research Centre European Social Fund (ESF)FCT - FCT-MEC (PIDDAC) FCOMP-01-0124-FEDER-029170 FCT PTDC/FIS-AST/3214/2012European Union (EU)Spanish Ministerio de Educacion, Cultura y Deporte by FPURamon y Cajal program from the Spanish Ministry of Economy and Competitiveness (MINECO) ATA2010-21322-C03-02European Union (EU) 303912European Career Re-integration GrantSpanish Government RyC-2011-09461 AYA2013-47742-C4-3-PEuropean Union (EU) FP7-PEOPLE-2013-IRSES-612701PTDC/FIS-AST/3214/2012Science & Technology Facilities Council (STFC) ST/K000985/

Novel genes and sex differences in COVID-19 severity

[EN] 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