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 Effect of Food Intake During Lactation and Early Pregnancy on Plasma Progesterone Concentrations and Prolificacy in Multiparous sows

High food intake in early pregnancy resulted in increased prenatal mortality and reduced subsequent litter size in many studies using gilts (den Hartog and Van Kempen, 1980). With multiparous sows there is generally no difference in the rate of embryo survival or litter size with high feeding in early pregnancy (Toplis et al, 1983, Dyck &amp; Cole, 1986).Limited evidence suggests that sows fed low levels in lactation and then a high level early in the following pregnancy may show increased rates of embryo mortality (Pike and Boaz, 1972; Hughes et al, 1984). The effect of high feeding may be due to low plasma progesterone concentrations (Hughes et al 1984; Dyck et al, 1980) in early pregnancy which may be associated with reduced embryo survival and litter size.This study was designed to investigate the effects of high or low feed intake in lactation and early pregnancy on plasma progesterone concentrations in early pregnancy and subsequent litter size using multiparous sows.</jats:p