The host genetic inborn errors of immunity (IEIs) have been shown to contribute to susceptibility to life-threatening coronavirus disease 2019 (COVID-19), as it had been associated previously with other viral infections. Most genetic association studies have described IEIs as a monogenic defect, while there have been no reports of patients with multiple inherited immune deficiencies. This is a complex case of IEIs predisposing to severe viral infections in an unvaccinated 33-year-old male patient.
View Article and Find Full Text PDFBackground: Autoantibodies have been demonstrated to dampen the interferon (IFN) response in viral infections. Elevated levels of these preexisting autoantibodies (aAbs) decrease basal interferon levels, increasing susceptibility to severe infections.
Objectives: This study aimed to evaluate the prevalence of type I IFN aAbs in both plasma and saliva from COVID-19 patients, analyze their neutralizing activity, and examine their associations with clinical outcomes, including the need for mechanical ventilation and in-hospital mortality.
Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.
View Article and Find Full Text PDFThere is emerging evidence that age-dependent differences in susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with stronger innate immune response in the upper respiratory tract in children compared to adults. The efficient induction of interferon (IFN) alpha and beta (α and β) signaling, and interferon-stimulated genes (ISGs) is fundamental to the host antiviral response. In-silico transcriptomic analyses was conducted to determine the expression levels of IFN α/β pathway genes as well as 524 human ISGs in upper and lower airways of children and adults at baseline and post respiratory infections including coronavirus disease 2019 (COVID-19).
View Article and Find Full Text PDFBackground: Patients with severe coronavirus disease 2019 (COVID-19) are at an increased risk of acute respiratory distress syndrome and mortality. This is due to the increased levels of pro-inflammatory cytokines that amplify downstream pathways that are controlled by immune regulators. Objective: This study aimed to investigate the association between cytokine genetic variants, cytokine serum levels/profiles, and disease severity in critically and noncritically ill COVID-19 patients.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19) was first identified in respiratory samples and was found to commonly cause cough and pneumonia. However, non-respiratory symptoms including gastrointestinal disorders are also present and a big proportion of patients test positive for the virus in stools for a prolonged period. In this cross-sectional study, we investigated viral load trends in stools and nasopharyngeal swabs and their correlation with multiple demographic and clinical factors.
View Article and Find Full Text PDFAlterations in the oral microbiota composition may influence mental health. However, linkages between compositional changes in the oral microbiota and their role in mental health among cigarette smokers remain largely unknown. In this study, we used shotgun metagenomics data for the oral microbiome of 105 participants.
View Article and Find Full Text PDFGlobal and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020.
View Article and Find Full Text PDFThe heterogeneous phenotypes among patients with coronavirus disease 2019 (COVID-19) has drawn worldwide attention, especially those with severe symptoms without comorbid conditions. Immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative virus of COVID-19, occur mainly by the innate immune response via the interferon (IFN)-mediated pathways, and the adaptive immunity via the T lymphocyte and the antibody mediated pathways. The ability of the original Wuhan SARS-CoV-2 strain, and possibly more so with new emerging variants, to antagonize IFN-mediated antiviral responses can be behind the higher early viral load, higher transmissibility, and milder symptoms compared to SARS-CoV and are part of the continued clinical evolution of COVID-19.
View Article and Find Full Text PDFAim: Type 2 Diabetes Mellitus (T2DM) is associated with microvascular complications, including diabetic retinopathy (DR), diabetic nephropathy (DNp), and diabetic peripheral neuropathy (DPN). In this study, we investigated genetic variations and Single Nucleotide Polymorphisms (SNPs) associated with DR, DNp, DPN and their combinations among T2DM patients of Arab origin from the United Arab Emirates, to establish the role of genes in the progression of microvascular diabetes complications.
Methods: A total of 158 Emirati patients with T2DM were recruited in this study.
The interplay between the compositional changes in the gastrointestinal microbiome, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and severity, and host functions is complex and yet to be fully understood. This study performed 16S rRNA gene-based microbial profiling of 143 subjects. We observed structural and compositional alterations in the gut microbiota of the SARS-CoV-2-infected group in comparison to non-infected controls.
View Article and Find Full Text PDFBackground: The heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. The objective of this manuscript is to conduct a trans-ancestry genome wide association study (GWAS) meta-analysis of COVID-19 severity to improve the understanding of potentially causal targets for SARS-CoV-2.
Methods: This cross-sectional study recruited 646 participants in the UAE that were divided into two phenotypic groups based on the severity of COVID-19 phenotypes, hospitalized (n=482) and non-hospitalized (n=164) participants.
The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection.
View Article and Find Full Text PDFCoronavirus infections have been a part of the animal kingdom for millennia. The difference emerging in the twenty-first century is that a greater number of novel coronaviruses are being discovered primarily due to more advanced technology and that a greater number can be transmitted to humans, either directly or an intermediate host. This has a range of effects from annual infections that are mild to full-blown pandemics.
View Article and Find Full Text PDFThe immune system is tightly regulated by the activity of stimulatory and inhibitory immune receptors. This immune homeostasis is usually disturbed during chronic viral infection. Using publicly available transcriptomic datasets, we conducted analyses to evaluate the expression pattern of 38 selected immune inhibitory receptors (IRs) associated with different myeloid and lymphoid immune cells during coronavirus disease 2019 (COVID-19) infection.
View Article and Find Full Text PDFBackground: Metabolic syndrome (MetS) contributes to increased risk of morbidity and mortality. The United Arab Emirates (UAE) has a high prevalence of MetS which may be linked to modifiable and genetic risk factors in the local population. The association between MetS as a phenotype and key genetic variants in the UAE has not been investigated.
View Article and Find Full Text PDFBackground: Two genome-wide association studies in European and Japanese populations reported on new loci for diabetic kidney disease (DKD), including FTO. In this study, we have replicated these investigations on a cohort of 410 Type 2 diabetes mellitus (T2DM) patients of Arab origin from the United Arab Emirates (UAE).
Methods And Results: The cohort included 145 diabetic patients diagnosed with DKD and 265 diabetics free of the disease.
Polymorphic Alu insertions (POALINs) are found throughout the human genome and have been used in various studies to infer geographic origin of human populations. The main aim of this study was to determine the allele and haplotype frequencies of five POALINs, AluHF, AluHG, AluHJ, AluTF and AluMICB, within the major histocompatibility complex (MHC) class I region of 95 UAE Arabs, and correlate their frequencies to those of the HLA-A, HLA-C and HLA-B class I allele lineages. Evolutionary relationships between the POALINs of the Arabs and those previously studied in populations of African, Asian and European descent were compared.
View Article and Find Full Text PDFThe high degree of polymorphism of the HLA system provides suitable genetic markers to study the diversity and migration of different world populations and is beneficial for forensic identification, anthropology, transplantation and disease associations. Although the United Arab Emirates (UAE) population of about nine million people is heterogeneous, information is limited for the HLA class I allele and haplotype frequencies of the Bedouin ethnic group. We performed low-resolution PCR-SSP genotyping of three HLA class I loci at HLA-A, -B and -C for 95 unrelated healthy Bedouins from the cities of Al Ain and Abu Dhabi in the UAE.
View Article and Find Full Text PDFObjectives: Within the Emirati population, risk factors and genetic predisposition to diabetic kidney disease (DKD) have not yet been investigated. The aim of this research was to determine potential clinical, laboratory and reported genetic loci as risk factors for DKD.
Research Design And Methods: Four hundred and ninety unrelated Emirati nationals with type 2 diabetes mellitus (T2DM) were recruited with and without DKD, and clinical and laboratory data were obtained.
Discoveries from the human genome, HapMap, and 1000 genome projects have collectively contributed toward the creation of a catalog of human genetic variations that has improved our understanding of human diversity. Despite the collegial nature of many of these genome study consortiums, which has led to the cataloging of genetic variations of different ethnic groups from around the world, genome data on the Arab population remains overwhelmingly underrepresented. The National Arab Genome project in the United Arab Emirates (UAE) aims to address this deficiency by using Next Generation Sequencing (NGS) technology to provide data to improve our understanding of the Arab genome and catalog variants that are unique to the Arab population of the UAE.
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