COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Studies of new Higgs boson interactions through nonresonant HH production in the b¯bγγ fnal state in pp collisions at √s = 13 TeV with the ATLAS detector

A search for nonresonant Higgs boson pair production in the b ¯bγγ fnal state is performed using 140 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. This analysis supersedes and expands upon the previous nonresonant ATLAS results in this fnal state based on the same data sample. The analysis strategy is optimised to probe anomalous values not only of the Higgs (H) boson self-coupling modifer κλ but also of the quartic HHV V (V = W, Z) coupling modifer κ2V . No signifcant excess above the expected background from Standard Model processes is observed. An observed upper limit µHH &lt; 4.0 is set at 95% confdence level on the Higgs boson pair production cross-section normalised to its Standard Model prediction. The 95% confdence intervals for the coupling modifers are −1.4 &lt; κλ &lt; 6.9 and −0.5 &lt; κ2V &lt; 2.7, assuming all other Higgs boson couplings except the one under study are fxed to the Standard Model predictions. The results are interpreted in the Standard Model efective feld theory and Higgs efective feld theory frameworks in terms of constraints on the couplings of anomalous Higgs boson (self-)interactions

Model-independent search for the presence of new physics in events including H → γγ with s \sqrt{s} = 13 TeV pp data recorded by the ATLAS detector at the LHC

Abstract A model-independent search for new physics leading to final states containing a Higgs boson, with a mass of 125.09 GeV, decaying to a pair of photons is performed with 139 fb−1 of s $$\sqrt{s}$$ = 13 TeV pp collision data recorded by the ATLAS detector at the Large Hadron Collider at CERN. This search examines 22 final states categorized by the objects that are produced in association with the Higgs boson. These objects include isolated electrons or muons, hadronically decaying τ-leptons, additional photons, missing transverse momentum, and hadronic jets, as well as jets that are tagged as containing a b-hadron. No significant excesses above Standard Model expectations are observed and limits on the production cross section at 95% confidence level are set. Detector efficiencies are reported for all 22 signal regions, which can be used to convert detector-level cross-section limits reported in this paper to particle-level cross-section constraints

Search for neutral long-lived particles in pp collisions at √s = 13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

A search for decays of pair-produced neutral long-lived particles (LLPs) is presented using 139 fb−1 of proton-proton collision data collected by the ATLAS detector at the LHC in 2015–2018 at a centre-of-mass energy of 13 TeV. Dedicated techniques were developed for the reconstruction of displaced jets produced by LLPs decaying hadronically in the ATLAS hadronic calorimeter. Two search regions are defined for different LLP kinematic regimes. The observed numbers of events are consistent with the expected background, and limits for several benchmark signals are determined. For a SM Higgs boson with a mass of 125 GeV, branching ratios above 10% are excluded at 95% confidence level for values of c times LLP mean proper lifetime in the range between 20 mm and 10 m depending on the model. Upper limits are also set on the cross-section times branching ratio for scalars with a mass of 60 GeV and for masses between 200 GeV and 1 TeV. [Figure not available: see fulltext.

Searches for lepton-flavour-violating decays of the Higgs boson into eτ and μτ in \sqrt{s} = 13 TeV pp collisions with the ATLAS detector

Abstract This paper presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ, performed using data collected with the ATLAS detector at the LHC. The searches are based on a data sample of proton-proton collisions at a centre-of-mass energy s $$\sqrt{s}$$ = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. Leptonic (τ → ℓνℓντ) and hadronic (τ → hadrons ντ) decays of the τ-lepton are considered. Two background estimation techniques are employed: the MC-template method, based on data-corrected simulation samples, and the Symmetry method, based on exploiting the symmetry between electrons and muons in the Standard Model backgrounds. No significant excess of events is observed and the results are interpreted as upper limits on lepton-flavour-violating branching ratios of the Higgs boson. The observed (expected) upper limits set on the branching ratios at 95% confidence level, B $$\mathcal{B}$$ (H → eτ) < 0.20% (0.12%) and B $$\mathcal{B}$$ (H → μτ ) < 0.18% (0.09%), are obtained with the MC-template method from a simultaneous measurement of potential H → eτ and H → μτ signals. The best-fit branching ratio difference, B $$\mathcal{B}$$ (H → μτ) → B $$\mathcal{B}$$ (H → eτ), measured with the Symmetry method in the channel where the τ-lepton decays to leptons, is (0.25 ± 0.10)%, compatible with a value of zero within 2.5σ