IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19

Interferons (IFNs) are a group of cytokines with antiviral, antiproliferative, antiangiogenic, and immunomodulatory activities. Type I IFNs amplify and propagate the antiviral response by interacting with their receptors, IFNAR1 and IFNAR2. In COVID-19, the IFNAR2 (interferon alpha and beta receptor subunit 2) gene has been associated with the severity of the disease, but the soluble receptor (sIFNAR2) levels have not been investigated. We aimed to evaluate the association of IFNAR2 variants (rs2236757, rs1051393, rs3153, rs2834158, and rs2229207) with COVID-19 mortality and to assess if there was a relation between the genetic variants and/or the clinical outcome, with the levels of sIFNAR2 in plasma samples from hospitalized individuals with severe COVID-19. We included 1,202 subjects with severe COVID-19. The genetic variants were determined by employing Taqman® assays. The levels of sIFNAR2 were determined with ELISA in plasma samples from a subgroup of 351 individuals. The rs2236757, rs3153, rs1051393, and rs2834158 variants were associated with mortality risk among patients with severe COVID-19. Higher levels of sIFNAR2 were observed in survivors of COVID-19 compared to the group of non-survivors, which was not related to the studied IFNAR2 genetic variants. IFNAR2, both gene, and soluble protein, are relevant in the clinical outcome of patients hospitalized with severe COVID-19

Immunothrombosis in COVID-19: Implications of Neutrophil Extracellular Traps

SARS-CoV-2 is a member of the family of coronaviruses associated with severe outbreaks of respiratory diseases in recent decades and is the causative agent of the COVID-19 pandemic. The recognition by and activation of the innate immune response recruits neutrophils, which, through their different mechanisms of action, form extracellular neutrophil traps, playing a role in infection control and trapping viral, bacterial, and fungal etiological agents. However, in patients with COVID-19, activation at the vascular level, combined with other cells and inflammatory mediators, leads to thrombotic events and disseminated intravascular coagulation, thus leading to a series of clinical manifestations in cerebrovascular, cardiac, pulmonary, and kidney disease while promoting severe disease and mortality. Previous studies of hospitalized patients with COVID-19 have shown that elevated levels of markers specific for NETs, such as free DNA, MPO, and H3Cit, are strongly associated with the total neutrophil count; with acute phase reactants that include CRP, D-dimer, lactate dehydrogenase, and interleukin secretion; and with an increased risk of severe COVID-19. This study analyzed the interactions between NETs and the activation pathways involved in immunothrombotic processes in patients with COVID-19

miRNAs, from Evolutionary Junk to Possible Prognostic Markers and Therapeutic Targets in COVID-19

The COVID-19 pandemic has been a public health issue around the world in the last few years. Currently, there is no specific antiviral treatment to fight the disease. Thus, it is essential to highlight possible prognostic predictors that could identify patients with a high risk of developing complications. Within this framework, miRNA biomolecules play a vital role in the genetic regulation of various genes, principally, those related to the pathophysiology of the disease. Here, we review the interaction of host and viral microRNAs with molecular and cellular elements that could potentiate the main pulmonary, cardiac, renal, circulatory, and neuronal complications in COVID-19 patients. miR-26a, miR-29b, miR-21, miR-372, and miR-2392, among others, have been associated with exacerbation of the inflammatory process, increasing the risk of a cytokine storm. In addition, increased expression of miR-15b, -199a, and -491 are related to the prognosis of the disease, and miR-192 and miR-323a were identified as clinical predictors of mortality in patients admitted to the intensive care unit. Finally, we address miR-29, miR-122, miR-155, and miR-200, among others, as possible therapeutic targets. However, more studies are required to confirm these findings

High Expression Levels of miR-21-5p in Younger Hospitalized COVID-19 Patients Are Associated with Mortality and Critical Disease

In COVID-19, critical disease and invasive mechanical ventilation (IMV) increase the risk of death, mainly in patients over 60 years of age. Objectives: To find the relationship between miR-21-5p and miR-146a-5p in terms of the severity, IMV, and mortality in hospitalized COVID-19 patients younger than 55 years of age. Methods: The patients were stratified according to disease severity using the IDSA/WHO criteria for severe and critical COVID-19 and subclassified into critical non-survivors and critical survivors. Results: Ninety-seven severe/critical COVID-19 patients were included; 81.3% of the deceased were male and 18.8% were female. Higher expression miR-21-5p levels were associated as follows: severe vs. critical disease (p = 0.007, FC = 0.498), PaO2/FiO2 index, mild vs. severe (p = 0.027, FC = 0.558), and survivors vs. non-survivors (p = 0.03, FC = 0.463). Moreover, we identified correlations with clinical variables: CRP (rho = −0.54, p p p p p < 0.001). Finally, miR-21-5p thresholds were calculated according to severity (8.191), IMV (8.191), and mortality (8.237); these values increased the risk of developing a critical disease (OR = 4.19), the need for IMV (OR = 5.63), and death (OR = 6.00). Conclusion: Increased expression levels of miR-21-5p are related to worse outcome of COVID-19 in younger hospitalized patients

Search for stealth supersymmetry in final states with two photons, jets, and low missing transverse momentum in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe results of a search for stealth supersymmetry in final states with two photons and jets, targeting a phase space region with low missing transverse momentum ($p_\text{T}^\text{miss}$), are reported. The study is based on a sample of proton-proton collisions at $\sqrt{s}$ =13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138 fb$^{-1}$. As LHC results continue to constrain the parameter space of the minimal supersymmetric standard model, the low $p_\text{T}^\text{miss}$ regime is increasingly valuable to explore. To estimate the backgrounds due to standard model processes in such events, we apply corrections derived from simulation to an estimate based on a control selection in data. The results are interpreted in the context of simplified stealth supersymmetry models with gluino and squark pair production. The observed data are consistent with the standard model predictions, and gluino (squark) masses of up to 2150 (1850) GeV are excluded at the 95% confidence level

Search for narrow trijet resonances in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe first search for narrow resonances decaying to three well-separated hadronic jets is presented. The search uses proton-proton collision data corresponding to an integrated luminosity of 138 fb$^{-1}$ at $\sqrt{s}$ = 13 TeV, collected at the CERN LHC. No significant deviations from the background predictions are observed between 1.75-9.00 TeV. The results provide the first mass limits on a right-handed boson Z$_{\mathrm{R}}$ decaying to three gluons, an excited quark decaying via a vector boson to three quarks, as well as updated limits on a Kaluza-Klein gluon decaying via a radion to three gluons

Observation of WWγ\gamma production and search for Hγ\gamma production in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe observation of WW$\gamma$ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138 fb$^{-1}$ is presented. The observed (expected) significance is 5.6 (4.7) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WW$\gamma$ is 6.0 $\pm$ 0.8 (stat) $\pm$ 0.7 (syst) $\pm$ 0.6 (modeling) fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks

Search for direct production of GeV-scale resonances decaying to a pair of muons in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for direct production of low-mass dimuon resonances is performed using $\sqrt{s}$ = 13 TeV proton-proton collision data collected by the CMS experiment during the 2017-2018 operation of the CERN LHC with an integrated luminosity of 96.6 fb$^{-1}$. The search exploits a dedicated high-rate trigger stream that records events with two muons with transverse momenta as low as 3 GeV but does not include the full event information. The search is performed by looking for narrow peaks in the dimuon mass spectrum in the ranges of 1.1-2.6 GeV and 4.2-7.9 GeV. No significant excess of events above the expectation from the standard model background is observed. Model-independent limits on production rates of dimuon resonances within the experimental fiducial acceptance are set. Competitive or world's best limits are set at 90% confidence level for a minimal dark photon model and for a scenario with two Higgs doublets and an extra complex scalar singlet (2HDM+S). Values of the squared kinetic mixing coefficient $\varepsilon^2$ in the dark photon model above 10$^{-6}$ are excluded over most of the mass range of the search. In the 2HDM+S, values of the mixing angle $\sin(\theta_\text{H})$ above 0.08 are excluded over most of the mass range of the search with a fixed ratio of the Higgs doublets vacuum expectation $\tan\beta$ = 0.5

Search for the lepton flavor violating τ→\tau \to 3μ\mu decay in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for the lepton flavor violating $\tau \to$ 3$\mu$ decay is performed using proton-proton collision events at a center-of-mass energy of 13 TeV collected by the CMS experiment at the LHC in 2017-2018, corresponding to an integrated luminosity of 97.7 fb$^{-1}$. Tau leptons produced in both heavy-flavor hadron and W boson decays are exploited in the analysis. No evidence for the decay is observed. The results of this search are combined with an earlier null result based on data collected in 2016 to obtain a total integrated luminosity of 131 fb$^{-1}$. The observed (expected) upper limits on the branching fraction $\mathcal{B}$($\tau \to$ 3$\mu$) at confidence levels of 90 and 95% are 2.9$\times$10$^{-8}$ (2.4$\times$10$^{-8}$) and 3.6$\times$10$^{-8}$ (3.0$\times$10$^{-8}$), respectively