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

Potencial alelopático de plantas de acapu (Vouacapoua americana): efeitos sobre plantas daninhas de pastagens Allelopathic potential of "acapu" (Vouacapoua americana) plants: effects on pasture weed

Extratos aquosos de folhas e cascas de plantas de acapu (Vouacapoua americana) foram preparados nas concentrações de 0, 1, 2, 3 e 5% (v/v), visando identificar e caracterizar a atividade potencialmente alelopática dessa espécie. Analisaram-se os efeitos dos extratos sobre a germinação de sementes e o alongamento da raiz primária das plantas daninhas malícia (Mimosa pudica) e malva (Urena lobata). Os bioensaios de germinação foram desenvolvidos em condições de 25 ºC e fotoperíodo de 12 horas. Para os bioensaios de alongamento da raiz primária, as condições estabelecidas foram de 25 ºC e fotoperíodo de 24 horas. Os resultados obtidos indicaram variações de respostas em função da fonte do extrato aquoso, do parâmetro analisado e da concentração do extrato. As reduções observadas tanto na germinação como no alongamento da raiz primária foram crescentes com o aumento da concentração do extrato, sendo os efeitos mais intensos observados na concentração de 5%. Independentemente da espécie receptora e do parâmetro analisado, o extrato preparado a partir das cascas do acapu evidenciou maior atividade alelopática inibitória. O alongamento da raiz primária foi o parâmetro mais sensível aos efeitos potencialmente alelopáticos do que a germinação das sementes. Comparativamente, cascas e folhas apresentaram diferenças em relação às classes de substâncias químicas. Nas cascas foram encontradas cumarinas que não estavam presentes nas folhas, as quais, por sua vez, apresentaram esteróides e triterpenóides, que não foram identificados nas cascas do acapu.<br>Aqueous extracts from leaves and bark of "Acapu" plants were prepared in concentration levels of 0, 1, 2, 3 and 5% to identify and characterize potential allelopathic activity of such plants. The extract effects on seed germination and primary root elongation of pasture weeds, such as Mimosa pudica and Urena lobata, were analyzed. The germination bioassays were developed under 25 ºC and a photoperiod of 12 hours. For the primary root elongation, the bioassay conditions were 25 ºC and photoperiod of 24 hours. The results indicated a variation in response, according to the source of aqueous extract, the analyzed parameter and the extract concentration. The reductions observed both in germination and primary root elongation increased with the increase of extract concentration. The most intense effects were observed at an extract concentration level of 5%. Regardless of the receiving species and the analyzed parameter, the extract prepared from the bark showed greater inhibiting allelopathic activity. The parameter primary root elongation was more sensitive to the potential allelopathic effects than seed germination. Comparatively, bark and leaves showed differences in relation to the chemical compound classes. Cumarins were identified in the bark but not in the leaves, while steroids and triterpenoids were observed in the leaves but not in the bark