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

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Not AvailableRabies is endemic in most parts of India, with the exception of Andaman and Nicobar, Lakshadweep islands and to some extent Nagaland. For prevention and control it is essential to rapidly and precisely diagnose rabies. In this study, we used three diagnostic methods, direct fluorescent antibody test (dFAT), reverse transcriptase polymerase chain reaction (RT-PCR) and real time reverse transcriptase polymerase chain reaction (RT-qPCR) to detect the rabies virus in suspected animal brains. Out of the 80 animal brain samples tested, 64 (80%) were positive for rabies according to the RT-qPCR. Compared to the RT-qPCR, the sensitivities of dFAT and RT-PCR were 95.31% and 96.88%, respectively. The specificities of dFAT and RT-PCR were on far with qRT-PCR. Even though the dFAT findings did not completely coincide with results obtained from RT-PCR and RT-qPCR, dFAT appears to be a fast and reliable assay that can be used to analyze fresh brain samples. But in countries like India where temperature reaches 50°C during summer and lack of diagnostic facilities and trained personnel to carry out the dFAT at field level, the suspected samples will be usually sent to National/Regional Disease Diagnostic Laboratory /State veterinary or agricultural universities for rabies diagnosis. In summary the molecular methods RT-PCR and RT-qPCR can serve as quick and rapid diagnostic methods for animal rabies in India.Not Availabl