Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

MUSiC: a model-unspecific search for new physics in proton–proton collisions at √s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton–proton collision data recorded at the LHC at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 35.9fb-1, are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches

Observation of Two Excited B-c(+) States and Measurement of the B-c(+) (2S) Mass in pp Collisions at root s=13 TeV

Signals consistent with the B-c(+)(2S) and B-c*(+)(2S) states are observed in proton-proton collisions at root s = 13 TeV, in an event sample corresponding to an integrated luminosity of 143 fb(-1), collected by the CMS experiment during the 2015-2018 LHC running periods. These excited (b) over barc states are observed in the B-c(+)pi(+)pi(-) invariant mass spectrum, with the ground state B-c(+) reconstructed through its decay to J/psi pi(+). The two states are reconstructed as two well-resolved peaks, separated in mass by 29.1 +/- 1.5(stat) +/- 0.7(syst) MeV. The observation of two peaks, rather than one, is established with a significance exceeding five standard deviations. The mass of the B-c(+)(2S) meson is measured to be 6871.0 +/- 1.2(stat) +/- 0.8(syst) +/- 0.8(B-c(+)) MeV, where the last term corresponds to the uncertainty in the world-average B-c(+) mass.Peer reviewe

Search for charged Higgs bosons in the H± → τ±ν_τ decay channel in proton-proton collisions at √s= 13 TeV

A search is presented for charged Higgs bosons in the H-+/- -> tau(+/-)nu(tau) decay mode in the hadronic final state and in final states with an electron or a muon. The search is based on proton-proton collision data recorded by the CMS experiment in 2016 at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). The results agree with the background expectation from the standard model. Upper limits at 95% confidence level are set on the production cross section times branching fraction to tau(+/-)nu(tau) for an H-+/- in the mass range of 80GeV to 3TeV, including the region near the top quark mass. The observed limit ranges from 6 pb at 80 GeV to 5 fb at 3 TeV. The limits are interpreted in the context of the minimal supersymmetric standard model m(h)(mod-) scenario.Peer reviewe

Measurement of double-parton scattering in inclusive production of four jets with low transverse momentum in proton-proton collisions at root s=13 TeV

A measurement of inclusive four-jet production in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. The transverse momenta of jets within vertical bar eta vertical bar 4.7 are required to exceed 35, 30, 25, and 20 GeV for the first-, second-, third-, and fourth-leading jet, respectively. Differential cross sections are measured as functions of the jet transverse momentum, jet pseudorapidity, and several other observables that describe the angular correlations between the jets. The measured distributions show sensitivity to different aspects of the underlying event, parton shower modeling, and matrix element calculations. In particular, the interplay between angular correlations caused by parton shower and double-parton scattering contributions is shown to be important. The double-parton scattering contribution is extracted by means of a template fit to the data, using distributions for single-parton scattering obtained from Monte Carlo event generators and a double-parton scattering distribution constructed from inclusive single-jet events in data. The effective double-parton scattering cross section is calculated and discussed in view of previous measurements and of its dependence on the models used to describe the single-parton scattering background

Electron and photon reconstruction and identification with the CMS experiment at the CERN LHC

The performance is presented of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC. The reported results are based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb(-1). Results obtained from lead-lead collision data collected at root S-NN = 5.02 TeV are also presented. Innovative techniques are used to reconstruct the electron and photon signals in the detector and to optimize the energy resolution. Events with electrons and photons in the final state are used to measure the energy resolution and energy scale uncertainty in the recorded events. The measured energy resolution for electrons produced in Z boson decays in proton-proton collision data ranges from 2 to 5%, depending on electron pseudorapidity and energy loss through bremsstrahlung in the detector material. The energy scale in the same range of energies is measured with an uncertainty smaller than 0.1 (0.3)% in the barrel (endcap) region in proton-proton collisions and better than 1(3)% in the barrel (endcap) region in heavy ion collisions. The timing resolution for electrons from Z boson decays with the full 2016-2018 proton-proton collision data set is measured to be 200 ps.Peer reviewe