15 research outputs found

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    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

    Economic valuation of preventing beach erosion: comparing existing and non-existing beach markets with stated and revealed preferences

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    Altres ajuts: CSO2013-42513-PPredicted climate change is likely to increase beach erosion in the future, inducing higher costs of beach maintenance. Hence, additional funds for their protection will be required. We examine the willingness to pay (WTP) of beach visitors for preventing beach erosion in the form of daily beach entrance fees in Crikvenica, Croatia, by applying the contingent valuation method. This is the first beach valuation study for this country in transition which has emerged as an important Mediterranean tourist destination. The novelty of our study is that it compares WTP estimates for an existing and a non-existing beach market. This is done by conducting a survey at the beach where an entrance fee is already levied and at the nearest open-access beach. Based on the initial (follow-up) valuation question the stated WTP per adult per day for avoiding beach erosion equals €1.69 (€1.26) for the paid beach and €2.08 (€1.84) for the free beach. In addition, the travel cost method is employed. It reveals that consumer surpluses for visiting the paid and the free beach amount to €2.57 and €1.74, respectively
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