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

Health promotion interventions for African Americans delivered in U.S. barbershops and hair salons- a systematic review

Background: African American adults suffer disproportionately from obesity-related chronic diseases, particularly at younger ages. In order to close the gap in these health disparities, efforts to develop and test culturally appropriate interventions are critical. Methods: A PRISMA-guided systematic review was conducted to identify and critically evaluate health promotion interventions for African Americans delivered in barbershops and hair salons. Subject headings and keywords used to search for synonyms of ‘barbershops,’ ‘hair salons,’ and ‘African Americans’ identified all relevant articles (from inception onwards) from six databases: Academic Search Ultimate, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Embase, PsycINFO, PubMed, Web of Science (Science Citation Index and Social Sciences Citation Index). Experimental and quasi-experimental studies for adult (> 18 years) African Americans delivered in barbershops and hair salons that evaluated interventions focused on risk reduction/management of obesity-related chronic disease: cardiovascular disease, cancer, and type 2 diabetes were included. Analyses were conducted in 2020. Results: Fourteen studies met criteria for inclusion. Ten studies hosted interventions in a barbershop setting while four took place in hair salons. There was substantial variability among interventions and outcomes with cancer the most commonly studied disease state (n = 7; 50%), followed by hypertension (n = 5; 35.7%). Most reported outcomes were focused on behavior change (n = 10) with only four studies reporting clinical outcomes. Conclusions: Health promotion interventions delivered in barbershops/hair salons show promise for meeting cancer screening recommendations and managing hypertension in African Americans. More studies are needed that focus on diabetes and obesity and utilize the hair salon as a site for intervention delivery. Trial registration: PROSPERO CRD42020159050. © 2021, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The evolutionary ecology of fatty-acid variation : Implications for consumer adaptation and diversification

The nutritional diversity of resources can affect the adaptive evolution of consumer metabolism and consumer diversification. The omega-3 long-chain polyunsaturated fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) have a high potential to affect consumer fitness, through their widespread effects on reproduction, growth and survival. However, few studies consider the evolution of fatty acid metabolism within an ecological context. In this review, we first document the extensive diversity in both primary producer and consumer fatty acid distributions amongst major ecosystems, between habitats and amongst species within habitats. We highlight some of the key nutritional contrasts that can shape behavioural and/or metabolic adaptation in consumers, discussing how consumers can evolve in response to the spatial, seasonal and community-level variation of resource quality. We propose a hierarchical trait-based approach for studying the evolution of consumers' metabolic networks and review the evolutionary genetic mechanisms underpinning consumer adaptation to EPA and DHA distributions. In doing so, we consider how the metabolic traits of consumers are hierarchically structured, from cell membrane function to maternal investment, and have strongly environment-dependent expression. Finally, we conclude with an outlook on how studying the metabolic adaptation of consumers within the context of nutritional landscapes can open up new opportunities for understanding evolutionary diversification