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

A Bioeconomic Analysis of a Shellfishery: The Effects of Recruitment and Habitat in a Metapopulation Model

This paper presents a bioeconomic model wherefishing effort exerted has multiple impacts onthe recruitment process of a sedentaryshellfish population. Recognizing thatsedentary populations generally possessmetapopulation characteristics at therecruitment stage, we show that fishing effortexerted not only influences the recruitmentprocess indirectly by limiting the number ofadults that spawn, but also directly byaffecting the habitat in which shellfish larvaerecruit. Depending on the recruitmentcharacteristics, fishing can have negative andpositive direct and indirect effects on therecruitment process. Next, a positive directeffect that fishing can have on the growth rateof the shellfish population if space to recruitto is limited is studied. Generalcharacteristics of sustainable fishing areanalyzed for the case that recruitment occursimmediately once spawning has occurred as wellas for the case that recruitment takes placeover a longer period of time. Conditions areidentified under which shellfishing should beencouraged in order to facilitate therecruitment process of juveniles. The paperends by analyzing how fishing alters theoptimal sustainable solution when itcontributes to habitat destruction. Copyright Kluwer Academic Publishers 2004fishing effort, habitat destruction, recruitment, shellfish, sustainable fishing,

Integrated models of fisheries management and policy

An overview of the structure and elements of integrated models aimed at studying fishery management policies using static and dynamic optimisation techniques is presented. Continuous and discrete time models are considered under both open-access and sole-owner settings. A variety of economic and biological processes that affect the fishery as a whole is examined. It turns out that overseeing important fish population characteristics such as metapopulation dynamics and multi-species interaction can lead to serious misrepresentation of the fishery and suboptimal controls. Adequate understanding of the economic conditions and considerations potentially affecting the fishermen is necessary to model their behaviour and address their concerns. Misrepresentation of these economic and biologic processes will have an impact on the success of management policies in attaining a sustainable fish population