49 research outputs found
Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of
Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N.
340541.
The Richards research group is supported by the Canadian Institutes of Health Research
(CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the
Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK,
Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in
Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported
by a research fellowship of the Japan Society for the Promotion of Science for Young
Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of
Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research
Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is
funded by the Welcome Trust, the Medical Research Council, the European Union, the
National Institute for Health Research-funded BioResource and the Clinical Research Facility
and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in
partnership with King’s College London. The Biobanque Québec COVID19 is funded by FRQS,
Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary
Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding
agencies had no role in the design, implementation or interpretation of this study.
The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of
Excellence 2167 “Precision Medicine in Chronic Inflammation (PMI)” (DFG Grant: “EXC2167”).
The COVID19-Host(a)ge study was supported by the German Federal Ministry of Education
and Research (BMBF) within the framework of the Computational Life Sciences funding
concept (CompLS grant 031L0165). Genotyping in COVID19-Host(a)ge was supported by a
philantropic donation from Stein Erik Hagen.
The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by
"Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by
the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from
COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de
Salud y Familias" of the Andalusian Government. DMM is currently funded by the the
Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018).
The Columbia University Biobank was supported by Columbia University and the National
Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official
views of the NIH or Columbia University.
The SPGRX study was supported by the Consejería de Economía, Conocimiento, Empresas y
Universidad #CV20-10150.
The GEN-COVID study was funded by: the MIUR grant “Dipartimenti di Eccellenza 2018-2020”
to the Department of Medical Biotechnologies University of Siena, Italy; the “Intesa San Paolo
2020 charity fund” dedicated to the project NB/2020/0119; and philanthropic donations to the
Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics
research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by
Tuscany Region “Bando Ricerca COVID-19 Toscana” grant to the Azienda Ospedaliero
Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA
consortium for providing computational resources; the Network for Italian Genomes (NIG)
(http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative
(https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon
Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for
managing specimens.
Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was
supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione
Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the
Dolce&Gabbana Fashion Firm is gratefully acknowledged.
Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione
IRCCS Cà Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca
Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS
Ca’ Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon
2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation:
Testing Marker Utility in Steatohepatitis”, Programme “Photonics” under grant agreement
“101016726” for the project “REVEAL: Neuronal microscopy for cell behavioural examination
and manipulation”, Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361. DP was
supported by Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della
Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV).
Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds
Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2)
study was supported by grants from Fondation Léon Fredericq and from Fonds de la
Recherche Scientifique (FNRS).
The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones
Científicas.
KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project
grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert
Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus
Bergvalls Stiftelse.
The COMRI cohort is funded by Technical University of Munich, Munich, Germany.
Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of
Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki,
Helsinki, Finland.
These funding agencies had no role in the design, implementation or interpretation of this
study.Background: There is considerable variability in COVID-19 outcomes amongst younger
adults—and some of this variation may be due to genetic predisposition. We characterized the
clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent
effect, using individual-level data in a large international multi-centre consortium.
Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by
the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive
patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this
genetic marker with mortality, COVID-19-related complications and laboratory values. We next
examined if the magnitude of these associations varied by age and were independent from
known clinical COVID-19 risk factors.
Findings: We found that rs10490770 risk allele carriers experienced an increased risk of
all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19
related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several
COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6),
venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI
1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure
(OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction
p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory
COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers,
compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes.
Prediction of death or severe respiratory failure among those ≤ 60 years improved when
including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770
risk allele was similar to, or better than, most established clinical risk factors.
Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with
increased risks of morbidity and mortality—and these are more pronounced amongst individuals
≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk
factors, suggesting potential implications for clinical risk management.Academy of
Finland Fellow grant N. 323116Academy of Finland for PREDICT consortium N.
340541.Canadian Institutes of Health Research
(CIHR) (365825 and 409511)Lady Davis Institute of the Jewish General HospitalCanadian Foundation for Innovation (CFI)NIH FoundationCancer Research UKGenome QuébecPublic Health Agency of CanadaMcGill Interdisciplinary Initiative in
Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS)Japan Society for the Promotion of Science for Young
ScientistsCIHR scholarship and a joint FRQS and Québec Ministry of
Health and Social Services scholarshipFRQS Clinical Research
ScholarshipCalcul QuébecCompute CanadaWelcome TrustMedical Research CouncEuropean UnionNational Institute for Health Research-funded BioResourceClinical Research Facility
and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation TrustKing’s College LondonGenome QuébecPublic Health Agency of CanadaMcGill Interdisciplinary
Initiative in Infection and ImmunityFonds de Recherche Québec Santé(DFG Grant: “EXC2167”)(CompLS grant 031L0165)Stein Erik Hagen"Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"Instituto de Salud Carlos III (CIBERehd and CIBERER)COVID-19-GWASCOVID-PREMED initiatives"Consejeria de
Salud y Familias" of the Andalusian GovernmentAndalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018)Columbia UniversityNational
Center for Advancing Translational SciencesNIH Grant Number UL1TR001873Consejería de Economía, Conocimiento, Empresas y
Universidad #CV20-10150MIUR grant “Dipartimenti di Eccellenza 2018-2020”“Intesa San Paolo
2020 charity fund” dedicated to the project NB/2020/0119Tuscany Region “Bando Ricerca COVID-19 Toscana”CINECA
consortiumNetwork for Italian Genomes (NIG)COVID-19 Host Genetics InitiativeGenetic Biobank of SienaEuroBioBankRD-ConnectRicerca Corrente (Italian Ministry of Health)Fondazione
Humanitas per la RicercaBanca Intesa San PaoloDolce&Gabbana Fashion FirmCOVID-19 BiobankFondazione
IRCCS Cà Granda MilanoMyFirst Grant AIRC n.16888Ricerca
Finalizzata Ministero della Salute RF-2016-02364358Ricerca corrente Fondazione IRCCS
Ca’ Granda Ospedale Maggiore PoliclinicoEuropean Union (EU) Programme Horizon
2020 (under grant agreement No. 777377)“Photonics” “101016726”Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della
Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV)"Fonds
Erasme"Fondation Léon FredericqFonds de la
Recherche Scientifique (FNRS)Consejo Superior de Investigaciones
CientíficasGerman Research Foundation (LU 1944/3-1)SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182)Swedish Research Council (2014-02569 and 2014-07606)Jeansson Stiftelser, Magnus
Bergvalls StiftelseTechnical University of Munich, Munich, GermanyGenotyping Laboratory of
Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki,
Helsinki, Finlan
Transancestral mapping and genetic load in systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL
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Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).
Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)
Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.
BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362
The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI
The GRAVITY instrument has been revolutionary for near-infrared
interferometry by pushing sensitivity and precision to previously unknown
limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer
(VLTI) in GRAVITY+, these limits will be pushed even further, with vastly
improved sky coverage, as well as faint-science and high-contrast capabilities.
This upgrade includes the implementation of wide-field off-axis
fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser
guide stars in an upgraded facility. GRAVITY+ will open up the sky to the
measurement of black hole masses across cosmic time in hundreds of active
galactic nuclei, use the faint stars in the Galactic centre to probe General
Relativity, and enable the characterisation of dozens of young exoplanets to
study their formation, bearing the promise of another scientific revolution to
come at the VLTI.Comment: Published in the ESO Messenge
Study of banana (Musa aaa Cavendish cv Nanica) trigger ripening for small scale process
Uso de parches protectores faciales no reduce la presión facial en un modelo simulado de ventilación mecánica no invasiva
Repeated doses of the perfluorocarbon FC-100 improve lung function of preterm lambs
Intratracheal administration of a single dose of the perfluorocarbon FC- 100 improves lung function in surfactant-deficient animals. In this study we compared the response to repeated doses of FC-100 (3 mL/kg 3% solution, n = 5) with that observed after administration of Exosurf (5 mL/kg, n = 5) to mechanically ventilated preterm lambs of 125 d of gestation. The initial dose of FC-100 rapidly increased arterial Po2, decreased arterial Pco2, and improved arterial pH. Also dynamic lung compliance markedly improved with this agent. Administration of an additional dose of FC-100 resulted in relatively similar changes, albeit of lesser magnitude than those observed with the initial dose. In contrast, Exosurf did not improve these variables even after three doses. All lambs treated with FC-100 survived the 6-h study period, whereas one of the five Exosurf-treated lambs survived (p < 0.05). Mean arterial blood pressure and heart rate decreased in those lambs that received FC-100, but not in
Prognosis of primary care patients aged 80 years and older with lower respiratory tract infection
BACKGROUND: Predictors for a complicated course of a lower respiratory tract infection (LRTI) episode among patients aged > or =80 years are unknown. AIM: To determine prognostic factors for hospital admission or death within 30 days after first onset of LRTI among primary care patients aged > or =80 years. DESIGN OF STUDY: Retrospective cohort study. SETTING: Utrecht General Practitioner Research Network. METHOD: Data were obtained using the computerised database of the research network over the years 1997 to 2003. Multivariable logistic regression analysis was applied to estimate the independent association of predictors with 30-day hospitalisation or death. RESULTS: In all, 860 episodes of LRTI were observed in 509 patients; 13% of patients were hospitalised or died within 30 days. Type of LRTI, diabetes, use of oral glucocorticoids, use of antibiotics in the previous month, and hospitalisation in the previous 12 months were independently associated with the combined outcome. Patients with insulin-dependent diabetes mellitus had a greater risk of 30-day hospitalisation or death compared with patients with non-insulin-dependent diabetes. CONCLUSION: Independent of age, serious comorbidity - notably the presence of insulin-dependent diabetes or exacerbation of chronic obstructive pulmonary disease requiring oral glucocorticoids - increases the risk for complications, including hospital admissions, in patients aged > or =80 years with an LRTI