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

Behavioural, emotional and family functioning of hospitalized children in China and Hong Kong

Purpose: This study examined behavioural and emotional problems, social competence and family functioning of hospitalized Chinese children in Hong Kong and the Chinese Mainland. Method: A sample of 210 hospitalized children (ages 2-11 years) and their families participated in the study. The families were from a cross-section of geographical areas in Hong Kong (two hospitals) and the Chinese Mainland (five hospitals). Parents completed an age-appropriate Chinese version of the Child Behaviour Checklist and the Family Assessment Device. Multiple regression models were used to examine predictors of children's behaviour problems. Results: Behavioural patterns appeared to be specific to the developmental stage. Children had greater problems when their families demonstrated poorer affective involvement. Hospitalized children on the Chinese Mainland experienced more internalizing and externalizing behaviour problems than those in Hong Kong. Sick children, according to their parents, however, demonstrate some resiliency based on social and academic competency factors. Conclusions: Hospitalized Chinese children manifest behavioural, emotional and family problems that vary by region, the child's development and gender. Problems predominantly of an internalizing nature characterized this group. The findings support the need for culturally appropriate behavioural assessments and interventions with hospitalized children.School of Nursin