12 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

    Ways to minimize bacterial infections, with special reference to Escherichia coli, to cope with the first-week mortality in chicks: An updated overview

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    On the commercial level, the poultry industry strives to find new techniques to combat bird's infection. During the first week, mortality rate increases in birds because of several bacterial infections of about ten bacterial species, especially colisepticemia. This affects the flock production, uniformity, and suitability for slaughter because of chronic infections. Escherichia coli (E. coli) causes various disease syndromes in poultry, including yolk sac infection (omphalitis), respiratory tract infection, and septicemia. The E. coli infections in the neonatal poultry are being characterized by septicemia. The acute septicemia may cause death, while the subacute form could be characterized through pericarditis, airsacculitis, and perihepatitis. Many E. coli isolates are commonly isolated from commercial broiler chickens as serogroups O1, O2, and O78. Although prophylactic antibiotics were used to control mortality associated with bacterial infections of neonatal poultry in the past, the commercial poultry industry is searching for alternatives. This is because of the consumer's demand for reduced antibiotic-resistant bacteria. Despite the vast and rapid development in vaccine technologies against common chicken infectious diseases, no antibiotic alternatives are commercially available to prevent bacterial infections of neonatal chicks. Recent research confirmed the utility of probiotics to improve the health of neonatal poultry. However, probiotics were not efficacious to minimize death and clinical signs associated with neonatal chicks' bacterial infections. This review focuses on the causes of the increased mortality in broiler chicks during the first week of age and the methods used to minimize death

    Ammonia emissions in poultry houses and microbial nitrification as a promising reduction strategy

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    High ammonia (NH3) levels (>25 ppm) in poultry houses reduce the body weight gain, feed conversion, survival ability, carcass conviction rate, and immune system of birds. High NH3 levels can also cause pain, eye-inflammation, and increased oxidative stress. The volatility rate of NH3 in poultry litter depends on the pH, humidity, ventilation rate, air velocity, manure nitrogen (N) content, and temperature. The litter's pH is a major factor regulating the volatilization of NH3because it specifies the volatile ammonium (NH4+)/NH3 ratio between their ionic and nonvolatile forms. High NH3 levels damage birds' respiratory systems' mucous membranes, thereby increasing their susceptibility to respiratory infections, particularly to Escherichia coli infection. In this review, the existing knowledge on soil-nitrifying bacteria and NH3 nitrification approaches for advancing poultry manure microbial nitrification and environmental implications of using various NH3 emission control techniques were summarized. Although few studies have focused on reducing NH3 volatilization by nitrification, nitrification is deemed a sustainable approach for reducing N excretions and controlling NH3 emissions in poultry houses. However, further studies are required to determine the most suitable soil nitrification bacteria to increase microbial nitrification
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