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

The Fourth Catalog of Active Galactic Nuclei Detected by the Fermi Large Area Telescope -- Data Release 3

International audienceAn incremental version of the fourth catalog of active galactic nuclei (AGNs) detected by the Fermi-Large Area Telescope is presented. This version (4LAC-DR3) derives from the third data release of the 4FGL catalog based on 12 years of E>50 MeV gamma-ray data, where the spectral parameters, spectral energy distributions (SEDs), yearly light curves, and associations have been updated for all sources. The new reported AGNs include 587 blazar candidates and four radio galaxies. We describe the properties of the new sample and outline changes affecting the previously published one. We also introduce two new parameters in this release, namely the peak energy of the SED high-energy component and the corresponding flux. These parameters allow an assessment of the Compton dominance, the ratio of the Inverse-Compton to the synchrotron peak luminosities, without relying on X-ray data

The Fourth Catalog of Active Galactic Nuclei Detected by the Fermi Large Area Telescope -- Data Release 3

An incremental version of the fourth catalog of active galactic nuclei (AGNs) detected by the Fermi-Large Area Telescope is presented. This version (4LAC-DR3) derives from the third data release of the 4FGL catalog based on 12 years of E>50 MeV gamma-ray data, where the spectral parameters, spectral energy distributions (SEDs), yearly light curves, and associations have been updated for all sources. The new reported AGNs include 587 blazar candidates and four radio galaxies. We describe the properties of the new sample and outline changes affecting the previously published one. We also introduce two new parameters in this release, namely the peak energy of the SED high-energy component and the corresponding flux. These parameters allow an assessment of the Compton dominance, the ratio of the Inverse-Compton to the synchrotron peak luminosities, without relying on X-ray data

The Fourth Catalog of Active Galactic Nuclei Detected by the Fermi Large Area Telescope -- Data Release 3

An incremental version of the fourth catalog of active galactic nuclei (AGNs) detected by the Fermi-Large Area Telescope is presented. This version (4LAC-DR3) derives from the third data release of the 4FGL catalog based on 12 years of E>50 MeV gamma-ray data, where the spectral parameters, spectral energy distributions (SEDs), yearly light curves, and associations have been updated for all sources. The new reported AGNs include 587 blazar candidates and four radio galaxies. We describe the properties of the new sample and outline changes affecting the previously published one. We also introduce two new parameters in this release, namely the peak energy of the SED high-energy component and the corresponding flux. These parameters allow an assessment of the Compton dominance, the ratio of the Inverse-Compton to the synchrotron peak luminosities, without relying on X-ray data

The Fourth Catalog of Active Galactic Nuclei Detected by the Fermi Large Area Telescope -- Data Release 3

An incremental version of the fourth catalog of active galactic nuclei (AGNs) detected by the Fermi-Large Area Telescope is presented. This version (4LAC-DR3) derives from the third data release of the 4FGL catalog based on 12 years of E>50 MeV gamma-ray data, where the spectral parameters, spectral energy distributions (SEDs), yearly light curves, and associations have been updated for all sources. The new reported AGNs include 587 blazar candidates and four radio galaxies. We describe the properties of the new sample and outline changes affecting the previously published one. We also introduce two new parameters in this release, namely the peak energy of the SED high-energy component and the corresponding flux. These parameters allow an assessment of the Compton dominance, the ratio of the Inverse-Compton to the synchrotron peak luminosities, without relying on X-ray data