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 hospitalization2–4 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

Ab initio CI calculation of the vibrational structure of the 1(nπ∗) transition in formaldehyde

This paper reports an ab initio CI calculation of the radiative 1A1¿1A2 transition of H2CO and D2CO. Throughout the calculation the electronic wavefunctions and transition moments are explicitly calculated as functions of the nuclear geometry, contrary to the conventional Herzberg–Teller approach. The evaluation of the vibrational wavefunctions and integrals was made numerically. The results show that the excited state frequency for mode 3 has to be reassigned and that the calculated vibrational structure agrees well with the experimental intensities

Measurement and modelling of evaporation from a coastal wetland in Maputaland, South Africa

The surface renewal (SR) method was used to determine the long-term (12 months) total evaporation (ET) from the Mfabeni Mire with calibration using eddy covariance during two window periods of approximately one week each. The SR method was found to be inexpensive, reliable and with low power requirements for unattended operation. <br><br> Despite maximum ET rates of up to 6.0 mm day<sup>−1</sup>, the average summer (October to March) ET was lower (3.2 mm day<sup>−1</sup>) due to early morning cloud cover that persisted until nearly midday at times. This reduced the daily available energy, and the ET was lower than expected despite the available water and high average wind speeds. In winter (May to September), there was less cloud cover but the average ET was only 1.8 mm day<sup>−1</sup> due to plant senescence. In general ET was suppressed by the inflow of humid air (low vapour pressure deficit) and the comparatively low leaf area index of the wetland vegetation. The accumulated ET over 12 months was 900 mm. Daily ET estimates were compared to the Priestley-Taylor model results and a calibration α = 1.0 (<i>R</i><sup>2</sup> = 0.96) was obtained for the site. A monthly crop factor (<i>K</i><sub>c</sub>) was determined for the standardised FAO-56 Penman-Monteith. However, <i>K</i><sub>c</sub> was variable in some months and should be used with caution for daily ET modelling. <br><br> These results represent not only some of the first long-term measurements of ET from a wetland in southern Africa, but also one of the few studies of actual ET in a subtropical peatland in the Southern Hemisphere. The study provides wetland ecologists and hydrologists with guidelines for the use of two internationally applied models for the estimation of wetland ET within a coastal, subtropical environment and shows that wetlands are not necessarily high water users