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

Mum or bub? Which influences breastfeeding loyalty

The need for social marketing research in the area of breastfeeding is highlighted by the failure of campaigns to increase breastfeeding rates over the past two decades in developed countries. This is despite evidence of the health benefits of longer breastfeeding duration to both baby and mother, and the high levels of expenditure on these campaigns. Whilst past campaign approaches typically focus on baby-oriented factors, breastfeeding is a complex behaviour that for many women involves barriers that influence their commitment to continued breastfeeding. Using social marketing, this research investigates the role of mother-centred factors on loyalty to breastfeeding. A sample of 405 Australian women completed an online survey. The data were analysed using structural equation modelling, which revealed that mother-oriented, rather than baby-oriented, factors influence attitudinal and behavioural loyalty to breastfeeding

Inter- and intra-hemispheric EEG coherence in patients with mild cognitive impairment at rest and during working memory task

Objective: To assess functional relationship by calculating inter- and intra-hemispheric electroencephalography (EEG) coherence at rest and during a working memory task of patients with mild cognitive impairment (MCI). Methods: The sample consisted of 69 subjects: 35 patients (n=17 males, n=18 females; 52~71 years old) and 34 normal controls (n=17 males, n=17 females; 51~63 years old). Mini-mental state examination (MMSE) of two groups revealed that the scores of MCI patients did not differ significantly from those of normal controls (P>0.05). In EEG recording, subjects were performed at rest and during working memory task. EEG signals from F3-F4, C3-C4, P3-P4, T5-T6 and O1-O2 electrode pairs are resulted from the inter-hemispheric action, and EEG signals from F3-C3, F4-C4, C3-P3, C4-P4, P3-O1, P4-O2, T5-C3, T6-C4, T5-P3 and T6-P4 electrode pairs are resulted from the intra-hemispheric action for delta (1.0~3.5 Hz), theta (4.0~7.5 Hz), alpha-1 (8.0~10.0 Hz), alpha-2 (10.5~13.0 Hz), beta-1 (13.5~18.0 Hz) and beta-2 (18.5~30.0 Hz) frequency bands. The influence of inter- and intra-hemispheric coherence on EEG activity with eyes closed was examined using fast Fourier transformation from the 16 sampled channels. Results: During working memory tasks, the inter- and intra-hemispheric EEG coherences in all bands were significantly higher in the MCI group in comparison with those in the control group (P<0.05). However, there was no significant difference in inter- and intra-hemispheric EEG coherences between two groups at rest. Conclusion: Experimental results comprise evidence that MCI patients have higher degree of functional connectivity between hemispheres and in hemispheres during working condition. It suggests that MCI may be associated with compensatory processes during working memory tasks between hemispheres and in hemispheres. Moreover, failure of normal cortical connections may exist in MCI patients