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

Substrate temperature dependence of structure and optical properties of ZnTiO3:Er3+/Yb3+ thin films synthesized by pulsed laser deposition

ZnTiO3:Er3+,Yb3+ thin film phosphors were successfully deposited by pulsed laser deposition (PLD) at different substrate temperatures. The distribution of the ions in the films was investigated and the chemical analysis showed that the doping ions were homogeneously distributed in the thin films. The optical response of the phosphors revealed that the reflectance percentages of the ZnTiO3:Er3+,Yb3+ vary with the silicon substrate temperature due to the differences in the thickness and morphological roughness of the thin films. Under 980 nm diode laser excitation, the ZnTiO3:Er3+,Yb3+ film phosphors displayed up-conversion emission from the Er3+ electronic transitions, with violet, blue, green, and red emission lines at 410, 480, 525, 545 and 660 nm from 2H9/2 → 4I15/2, 4F7/2 → 4I15/2, 2H11/2 → 4I15/2, 4S3/2 → 4I15/2 and 4F9/2 → 4I15/2 transitions, respectively. The up-conversion emission was enhanced by increasing the silico (Si) substrate temperature during the deposition. Based on the photoluminescence properties and decay lifetime analysis, the energy level diagram was established and the up-conversion energy-transfer mechanism was discussed in detail

TOF SIMS analysis, structure and photoluminescence properties of pulsed laser deposited CaS:Eu2+ thin films

CaS:Eu2þ thin films weredepositedonSi(100)substratesusingthepulsedlaserdepositiontechniqueto investigatetheeffectofargon(Ar),oxygen(O2), andvacuumdepositionatmospheresonthestructural, morphological andphotoluminescencepropertiesofthethin films. Thephosphortargetwasablated using a266nmNd:YAGlaser.X-raydiffraction,atomicforcemicroscopy,scanningelectronmicroscopy, energy dispersiveX-ray, fluorescencespectrophotometryandtime-of-flight secondaryionmassspec- trometry wereusedtocharacterizethethin films. Thethin films preparedinoxygenwereessentially amorphous, whilethosepreparedinargonandvacuumshowedsomedegreeofcrystallinity.The film deposited inArshowedbetterphotoluminescenceintensitythanthosedepositedinanO2 and vacuum. The emissionobservedataround650nmforallthe films isattributedtothetransitionsfromtheexcited 4f F 5dt 6 0 7 1 [ ] ( 2g) state tothegroundstate 4f7 S 7/2 8 ( ) of theEu2þ ions. Theemissionat618nm,whichismore prominent inthe film preparedinO2, isascribedtothe 5D F 0 2 7 → transitions inEu3þ, suggestingthatEu2þ wasunintentionallyoxidizedtoEu3þ. Theatomicforcemicroscopydatashowedthatthe film prepared in argonwasrougherthanthosepreparedinoxygenandvacuum.This workwas financially supportedbythecompetitivepro- gramme forratedresearchers(Grantno.CPR20110724000021870) of theSouthAfricanNationalResearchFoundation(NRF),the South AfricanResearchChairsInitiativeoftheDepartmentof Science andTechnology(Grantno.84415)therentalpoolpro- grammeoftheNationalLaserCentre(NLC)(Grantno.NLC- LREGM00-CON-001).CaS:Eu2þ thin films weredepositedonSi(100)substratesusingthepulsedlaserdepositiontechniqueto investigatetheeffectofargon(Ar),oxygen(O2), andvacuumdepositionatmospheresonthestructural, morphological andphotoluminescencepropertiesofthethin films. Thephosphortargetwasablated using a266nmNd:YAGlaser.X-raydiffraction,atomicforcemicroscopy,scanningelectronmicroscopy, energy dispersiveX-ray, fluorescencespectrophotometryandtime-of-flight secondaryionmassspec- trometry wereusedtocharacterizethethin films. Thethin films preparedinoxygenwereessentially amorphous, whilethosepreparedinargonandvacuumshowedsomedegreeofcrystallinity.The film deposited inArshowedbetterphotoluminescenceintensitythanthosedepositedinanO2 and vacuum. The emissionobservedataround650nmforallthe films isattributedtothetransitionsfromtheexcited 4f F 5dt 6 0 7 1 [ ] ( 2g) state tothegroundstate 4f7 S 7/2 8 ( ) of theEu2þ ions. Theemissionat618nm,whichismore prominent inthe film preparedinO2, isascribedtothe 5D F 0 2 7 → transitions inEu3þ, suggestingthatEu2þ wasunintentionallyoxidizedtoEu3þ. Theatomicforcemicroscopydatashowedthatthe film prepared in argonwasrougherthanthosepreparedinoxygenandvacuum

Photoluminescence and phase related cathodoluminescence dynamics of Pr3+ doped in a double phase of ZnTa2O6 and ZnAl2O4

A new phosphor ZnTaAlO5:Pr3+, which displays cathodoluminescence intensity that is phase dependent, was synthesised by solid statereaction. x-ray diffraction, scanning electron microscopy and EDX (energy dispersive x-ray spectroscopy) maps were used to confirm the multi-phase, multi-particle shapes and to assign each particle shape o a corresponding phase of the phosphor, respectively. Cathodoluminescence mapswere obtained simultaneously with the EDX maps, and showed both the luminescence emerging from intrinsic and extrinsic defect centres. Theactivator red emission was better resolved using photoluminescence spectroscopy, which showed emission lines emerging from more than onemanifold of the Pr3+transitions. The persistent luminescence was measured and the corresponding electron trapping centres were characterisedby thermoluminescence spectroscopy.This work is based on financial contribution from the South African Research Chairs Initiative of the Department of Science and Technology (84415), National Research Foundation of South Africa and the Erasmus Mundus–Saturn action 2 programme funded by the European Union (2014/2015).A new phosphor ZnTaAlO5:Pr3+, which displays cathodoluminescence intensity that is phase dependent, was synthesised by solid statereaction. x-ray diffraction, scanning electron microscopy and EDX (energy dispersive x-ray spectroscopy) maps were used to confirm the multi-phase, multi-particle shapes and to assign each particle shape o a corresponding phase of the phosphor, respectively. Cathodoluminescence mapswere obtained simultaneously with the EDX maps, and showed both the luminescence emerging from intrinsic and extrinsic defect centres. Theactivator red emission was better resolved using photoluminescence spectroscopy, which showed emission lines emerging from more than onemanifold of the Pr3+transitions. The persistent luminescence was measured and the corresponding electron trapping centres were characterisedby thermoluminescence spectroscopy