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

Determination of the critical period of weed control in corn using a thermal basis Determinação do período crítico de controle de plantas daninhas em milho utilizando uma base térmica

Field studies were conducted over 3 years in southeast Buenos Aires, Argentina, to determine the critical period of weed control in maize (Zea mays L.). The treatments consisted of two different periods of weed interference, a critical weed-free period, and a critical time of weed removal. The Gompertz and logistic equations were fitted to relative yields representing the critical weed-free and the critical time of weed removal, respectively. Accumulated thermal units were used to describe each period of weed-free or weed removal. The critical weed-free period and the critical time of weed removal ranged from 222 to 416 and 128 to 261 accumulated thermal units respectively, to prevent yield losses of 2.5%. Weed biomass proved to be inverse to the crop yield for all the years studied. When weeds competed with the crop from emergence, a large increase in weed biomass was achieved 10 days after crop emergence. However, few weed seedlings emerged and prospered after the 5-6 leaf maize stage (10-20 days after emergence).<br>Conduziram-se estudos no campo durante três anos no sudeste da Província de Buenos Aires, Argentina, para determinar o período crítico de controle de plantas daninhas no milho. Os tratamentos consistiram de dois períodos diferentes de interferência das plantas daninhas: um período crítico livre de plantas daninhas, e um período crítico de remoção de plantas daninhas. O período crítico livre de plantas daninhas foi ajustado por meio da equação Gompertz, enquanto o período crítico de remoção de plantas daninhas foi ajustado mediante a equação logística. Foram utilizadas as unidades térmicas para descrever cada período de interferência de plantas daninhas. O período crítico livre e o período crítico de remoção de plantas daninhas variaram de 222 a 416 e de 128 a 261 unidades térmicas acumuladas, respectivamente, para impedir uma perda de rendimento de 2,5%. A biomassa das plantas daninhas variou ao contrário do rendimento do cultivo, em todos os anos estudados. Quando as plantas daninhas competiram com o cultivo desde a emergência, foi alcançado um grande incremento de biomassa aos dez dias após a emergência do cultivo. Porém, poucas plântulas de plantas daninhas emergiram e prosperaram depois do estádio de 5-6 folhas de milho (10-20 dias após a emergência)