Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Software performance of the ATLAS track reconstruction for LHC run 3

Charged particle reconstruction in the presence of many simultaneous proton–proton (pp) collisions in the LHC is a challenging task for the ATLAS experiment’s reconstruction software due to the combinatorial complexity. This paper describes the major changes made to adapt the software to reconstruct high-activity collisions with an average of 50 or more simultaneous pp interactions per bunch crossing (pileup) promptly using the available computing resources. The performance of the key components of the track reconstruction chain and its dependence on pile-up are evaluated, and the improvement achieved compared to the previous software version is quantified. For events with an average of 60 pp collisions per bunch crossing, the updated track reconstruction is twice as fast as the previous version, without significant reduction in reconstruction efficiency and while reducing the rate of combinatorial fake tracks by more than a factor two

Search for heavy Majorana or Dirac neutrinos and right-handed W gauge bosons in final states with charged leptons and jets in pp collisions at √s = 13 TeV with the ATLAS detector

A search for heavy right-handed Majorana or Dirac neutrinos NR and heavy right-handed gauge bosons WR is performed in events with energetic electrons or muons, with the same or opposite electric charge, and energetic jets. The search is carried out separately for topologies of clearly separated final-state products (“resolved” channel) and topologies with boosted final states with hadronic and/or leptonic products partially overlapping and reconstructed as a large-radius jet (“boosted” channel). The events are selected from pp collision data at the LHC with an integrated luminosity of 139 fb−1 collected by the ATLAS detector at √s = 13 TeV. No significant deviations from the Standard Model predictions are observed. The results are interpreted within the theoretical framework of a left-right symmetric model, and lower limits are set on masses in the heavy righthanded WR boson and NR plane. The excluded region extends to about m(WR) = 6.4 TeV for both Majorana and Dirac NR neutrinos at m(NR) < 1 TeV. NR with masses of less than 3.5 (3.6) TeV are excluded in the electron (muon) channel at m(WR) = 4.8 TeV for the Majorana neutrinos, and limits of m(NR) up to 3.6 TeV for m(WR) = 5.2 (5.0) TeV in the electron (muon) channel are set for the Dirac neutrinos. These constitute the most stringent exclusion limits to date for the model considered

Observation of four-top-quark production in the multilepton final state with the ATLAS detector

This paper presents the observation of four-top-quark (tt¯tt¯) production in proton-proton collisions at the LHC. The analysis is performed using an integrated luminosity of 140 fb−1 at a centre-of-mass energy of 13 TeV collected using the ATLAS detector. Events containing two leptons with the same electric charge or at least three leptons (electrons or muons) are selected. Event kinematics are used to separate signal from background through a multivariate discriminant, and dedicated control regions are used to constrain the dominant backgrounds. The observed (expected) significance of the measured tt¯tt¯ signal with respect to the standard model (SM) background-only hypothesis is 6.1 (4.3) standard deviations. The tt¯tt¯ production cross section is measured to be 22.5+6.6−5.5 fb, consistent with the SM prediction of 12.0±2.4 fb within 1.8 standard deviations. Data are also used to set limits on the three-top-quark production cross section, being an irreducible background not measured previously, and to constrain the top-Higgs Yukawa coupling and effective field theory operator coefficients that affect tt¯tt¯ production

Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

Search for heavy Higgs bosons with flavour-violating couplings in multi-lepton plus b-jets final states in pp collisions at 13 TeV with the ATLAS detector

A search for new heavy scalars with flavour-violating decays in final states with multiple leptons and b-tagged jets is presented. The results are interpreted in terms of a general two-Higgs-doublet model involving an additional scalar with couplings to the top-quark and the three up-type quarks (ρtt, ρtc, and ρtu). The targeted signals lead to final states with either a same-sign top-quark pair, three top-quarks, or four top-quarks. The search is based on a data sample of proton-proton collisions at √s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Events are categorised depending on the multiplicity of light charged leptons (electrons or muons), total lepton charge, and a deep-neural-network output to enhance the purity of each of the signals. Masses of an additional scalar boson mH between 200 − 630 GeV with couplings ρtt = 0.4, ρtc = 0.2, and ρtu = 0.2 are excluded at 95% confidence level. Additional interpretations are provided in models of R-parity violating supersymmetry, motivated by the recent flavour and (g − 2)μ anomalies

Search for a new heavy scalar particle decaying into a Higgs boson and a new scalar singlet in final states with one or two light leptons and a pair of τ-leptons with the ATLAS detector

A search for a new heavy scalar particle X decaying into a Standard Model (SM) Higgs boson and a new singlet scalar particle S is presented. The search uses a proton-proton (pp) collision data sample with an integrated luminosity of 140 fb−1 recorded at a centre-of-mass energy of s√ = 13 TeV with the ATLAS detector at the Large Hadron Collider. The most sensitive mass parameter space is explored in X mass ranging from 500 to 1500 GeV, with the corresponding S mass in the range 200–500 GeV. The search selects events with two hadronically decaying τ-lepton candidates from H → τ+τ− decays and one or two light leptons (ℓ = e, μ) from S → VV (V = W, Z) decays while the remaining V boson decays hadronically or to neutrinos. A multivariate discriminant based on event kinematics is used to separate the signal from the background. No excess is observed beyond the expected SM background and 95% confidence level upper limits between 72 fb and 542 fb are derived on the cross-section σ(pp → X → SH) assuming the same SM-Higgs boson-like decay branching ratios for the S → VV decay. Upper limits on the visible cross-sections σ(pp → X → SH → WWττ) and σ(pp → X → SH → ZZττ) are also set in the ranges 3–26 fb and 6–33 fb, respectively

The ATLAS trigger system for LHC Run 3 and trigger performance in 2022

The ATLAS trigger system is a crucial component of the ATLAS experiment at the LHC. It is responsible for selecting events in line with the ATLAS physics programme. This paper presents an overview of the changes to the trigger and data acquisition system during the second long shutdown of the LHC, and shows the performance of the trigger system and its components in the proton-proton collisions during the 2022 commissioning period as well as its expected performance in proton-proton and heavy-ion collisions for the remainder of the third LHC data-taking period (2022–2025)