SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

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 hospitalization2–4 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

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

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 first update on mapping the human genetic architecture of COVID-19

peer reviewe

Effects of resident education and self-implementation of integrated pest management strategy for eliminating bed bug infestation in Ahvaz city, southwestern Iran

Background: Bed bugs as blood-sucking insects have become a public health problem in urban communities throughout the world. The objective of this study was to determine the effects of resident education and self-implementation of Integrated Pest Management (IPM) strategy for eliminating bed bug infestation in infected apartments in Ahvaz City, Iran. Methods: This interventional study was conducted in seventy apartments infested with bed bug (Cimex lectularius) in Ahvaz City, southwest Iran, during a 6-month period. The bed bug infestations reported to Health centers were inspected visually and confirmed by medical entomology experts. Then, the heads of the households were received techniques/tools of the IPM program and trained by medical entomology experts before self-implementation of control methods. Finally, the infected apartments were inspected by the experts at 1, 3, and 6 months after intervention and data were recorded in a checklist. Results: From the seventy infected apartments, 57, 28 and 15 were considered as low, moderate, and high level infestation respectively. The bed bug infestation was eliminated from 53 apartments (76) after one month and it reached to 62 apartments (88) by the end of third month. Finally, after six months of applying IPM program, bed bugs infestation was eliminated from all infected apartments (100). Residents expressed their 100 satisfaction with applying the bed bug IPM strategy. Conclusion: Training residents to implement the IPM program can reduce pest control costs, the volume of pesticides consumed, and human exposure to chemical pesticides, resulting in increased human and environmental health and safety. © 2020 Tehran University of Medical Sciences. All rights reserved

Prevalence and spatial distribution of bed bug, Cimex lectularius, infestation in Southwest of Iran: GIS approach

Background: The common bed bug, a nocturnal bloodsucking insect, is known as a human parasite and public health problem in the world. The prevalence and geographical dispersion of bed bug in Ahvaz City, southwest of Iran was measured. Methods: Spatial distribution of Cimex lectularius was determined by surveying 520 houses in 62 areas of Ahvaz City in 2017. Some information like as infested points, the concern level of the residents and allergic reaction to the insect bite were registered in a form using the secondhand instrument. Results: According to the spatial distribution map, of 62 areas, 27 of them are infested with bed bugs. Infestation is scattered throughout the city, but its focus is on the east of the Karun River. The most bed bug infestation was in Asiabad followed by Manbaab areas. Prevalence of bed bug infestation estimated 9.61 in Ahvaz city. It was 5.4 and 11.6 in apartments and single houses, respectively. The lowest and highest infestation rates based on its source were 1.35 and 9.03 in wallpaper and cracks and crevices, respectively. Bedroom and sitting room were the main harborages for bed bug in the houses. The majority of residents who had bitten by a bed bug showed various allergic reactions like redness skin, papules, vesicles, pustules and blisters. Most of the people in the infested houses (62) were very concern about bed bug infestation. Conclusion: Public education and increasing the knowledge of people can lead to successful management, prevention and elimination of this nuisance pest. © 2020 Tehran University of Medical Sciences. All rights reserved

The first report of drug resistant bacteria isolated from the brown-banded cockroach, supella longipalpa, in Ahvaz, South-western Iran

Background: The brown-banded cockroach, Supella longipalpa is known as a carrier of pathogenic bacteria in urban environments, but its role is not well documented regarding the carriage of antibiotic-resistant pathogenic bacteria in Iran. The aim of this study was to determine the resistance bacteria isolated from the brown-banded cockroach in Ahvaz, south west of Iran. Methods: Totally 39 cockroaches were collected from kitchen area of houses and identified. All specimens were cultured to isolate the bacterial agents on blood agar and MacConky agar media. The microorganisms were identified using necessary differential and biochemical tests. Antimicrobial susceptibility tests were performed for isolated organisms by Kirby-Bauer's disk diffusion according to NCLI guideline, using 18 antibiotics. Results: From the 39 collected S. langipalpa, 179 bacterial agents were isolated, 92 of alimentary ducts and 87 of external body surfaces. Isolated bacteria from cockroaches were identified as Enterobacter spp., Klebsiella spp., Citrobacter spp., Escherichia coli, Salmonella spp., Proteus spp., coagulase negative staphylococci, Serratia marcescens, Staphylococcus aureus, and Bacillus species. The pattern resistance rates were determined for gram negative bacilli and gram positive cocci regarding 18 antibiotics. Conclusion: The brown-banded cockroach can be involved in the spread of drug resistant bacteria and increases the possibility of contacting human environment to drug resistant bacteria. Therefore, the potential of removing this insect should be improved. This is the first original report of drug resistant bacteria isolated from the brown-banded cockroach of Iran