Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: a review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

Understanding tumour endothelial cell heterogeneity and function from single-cell omics.

Anti-angiogenic therapies (AATs) are used to treat different types of cancers. However, their success is limited owing to insufficient efficacy and resistance. Recently, single-cell omics studies of tumour endothelial cells (TECs) have provided new mechanistic insight. Here, we overview the heterogeneity of human TECs of all tumour types studied to date, at the single-cell level. Notably, most human tumour types contain varying numbers but only a small population of angiogenic TECs, the presumed targets of AATs, possibly contributing to the limited efficacy of and resistance to AATs. In general, TECs are heterogeneous within and across all tumour types, but comparing TEC phenotypes across tumours is currently challenging, owing to the lack of a uniform nomenclature for endothelial cells and consistent single-cell analysis protocols, urgently raising the need for a more consistent approach. Nonetheless, across most tumour types, universal TEC markers (ACKR1, PLVAP and IGFBP3) can be identified. Besides angiogenesis, biological processes such as immunomodulation and extracellular matrix organization are among the most commonly predicted enriched signatures of TECs across different tumour types. Although angiogenesis and extracellular matrix targets have been considered for AAT (without the hoped success), the immunomodulatory properties of TECs have not been fully considered as a novel anticancer therapeutic approach. Therefore, we also discuss progress, limitations, solutions and novel targets for AAT development.

Microvascular and macrovascular complications of type 2 diabetes mellitus: Exome wide association analyses.

Background: Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and ß-cell impairment lead to hyperglycemia, influenced by genetic and environmental factors. T2DM is associated with long-term complications that have contributed to the burden of morbidity and mortality worldwide. The objective of this manuscript is to conduct an Exome-Wide Association Study (EWAS) on T2DM Emirati individuals to improve our understanding on diabetes-related complications to improve early diagnostic methods and treatment strategies. Methods: This cross-sectional study recruited 310 Emirati participants that were stratified according to their medically diagnosed diabetes-related complications: diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and cardiovascular complications. The Illumina's Infinium Exome-24 array was used and 39,840 SNPs remained for analysis after quality control. Findings: The analysis revealed the associations of various genes with each complication category: 1) diabetic retinopathy was associated to SHANK3 gene in locus 22q13.33 (SNP rs9616915; p=5.18 x10-4), ZSCAN5A gene in locus 19q13.43 (SNP rs7252603; p=7.55 x10-4), and DCP1B gene in locus 12p13.33 (SNPs rs715146, rs1044950, rs113147414, rs34730825; p=7.62 x10-4); 2) diabetic neuropathy was associated to ADH4 gene in locus 4q23 (SNP rs4148883; p=1.23 x10-4), SLC11A1 gene in locus 2q35 (SNP rs17235409; p=1.85 x10-4), and MATN4 gene in locus 20q13.12 (SNP rs2072788; p=2.68 x10-4); 3) diabetic nephropathy was associated to PPP1R3A gene in locus 7q31.1 (SNP rs1799999; p=1.91 x10-4), ZNF136 gene in locus 19p13.2 (SNP rs140861589; p=2.80 x10-4), and HSPA12B gene in locus 20p13 (SNP rs6076550; p=2.86 x10-4); and 4) cardiovascular complications was associated to PCNT gene in locus 21q22.3 (SNPs rs7279204, rs6518289, rs2839227, rs2839223; p=2.18 x10-4,3.04 x10-4,4.51 x10-4,5.22 x10-4 respectively), SEPT14 gene in locus 7p11.2 (SNP rs146350220; p=2.77 x10-4), and WDR73 gene in locus 15q25.2 (SNP rs72750868; p=4.47 x10-4). Interpretation: We have identified susceptibility loci associated with each category of T2DM-related complications in the Emirati population. Given that only 16% of the markers from the Illumina's Infinium Exome chip passed quality control assessment, this demonstrates that multiple variants were, either, monomorphic in the Arab population or were not genotyped due to the use of a Euro-centric EWAS array that limits the possibility of including targeted ethnic-specific SNPs. Our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci associated to T2DM complications. Further effort must be conducted to improve the representation of diverse populations in genotyping and sequencing studies.

Whole-Exome Sequencing in Family Trios Reveals De Novo Mutations Associated with Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency and loss of pancreatic islet ß-cells. The objective of this study is to identify de novo mutations in 13 trios from singleton families that contribute to the genetic basis of T1DM through the application of whole-exome sequencing (WES). Of the 13 families sampled for this project, 12 had de novo variants, with Family 7 having the highest number (nine) of variants linked to T1DM/autoimmune pathways, whilst Family 4 did not have any variants past the filtering steps. There were 10 variants of 7 genes reportedly associated with T1DM (MST1; TDG; TYRO3; IFIHI; GLIS3; VEGFA; TYK2). There were 20 variants of 13 genes that were linked to endocrine, metabolic, or autoimmune diseases. Our findings demonstrate that trio-based WES is a powerful approach for identifying new candidate genes for the pathogenesis of T1D. Genotyping and functional annotation of the discovered de novo variants in a large cohort is recommended to ascertain their association with disease pathogenesis.

Risk of hospitalization and vaccine effectiveness among COVID-19 patients in the UAE during the Delta and Omicron outbreaks.

Introduction: A rapid increase in COVID-19 cases due to the spread of the Delta and Omicron variants in vaccinated populations has raised concerns about the hospitalization risk associated with, and the effectiveness of, COVID-19 vaccines. Method: This case-control study aims to determine the hospitalization risk associated with the inactivated BBIBP-CorV (Sinopharm) and mRNA BNT162b2 (Pfizer-BionTech) vaccines, and their effectiveness reducing the rate of hospital admission between 28 May 2021 and 13 January 2022, during the Delta and Omicron outbreaks. The estimation of vaccine effectiveness of 4,618 samples was based on the number of patients hospitalized at different vaccination statuses, adjusted for confounding variables. Results: Hospitalization risk increases in patients affected with the Omicron variant if patients are aged ≤ 18 years (OR 6.41, 95% CI 2.90 to 14.17; p < 0.001), and in patients affected with the Delta variant if they are aged > 45 years (OR 3.41, 95% CI 2.21 to 5.50; p < 0.001). Vaccine effectiveness reducing the rate of hospital admission for fully vaccinated participants infected with the Delta and Omicron variants was similar for both the BBIBP-CorV (94%, 95% CI 90% to 97%; 90%, 95% CI 74% to 96%) and BNT162b2 vaccines (95%, 95% CI 61% to 99.3%; 94%, 95% CI 53% to 99%), respectively. Discussion: The BBIBP-CorV and BNT162b2 vaccines utilized in the UAE vaccination program were highly effective in reducing the rate of COVID-19-related hospitalization during the Delta and Omicron outbreaks, and further effort must be taken to achieve high vaccine coverage rates in children and adolescents in the global context to reduce the hospitalization risk associated with COVID-19 on an international scale.

A genome-wide association study identifies a possible role for cannabinoid signalling in the pathogenesis of diabetic kidney disease.

Diabetic kidney disease (DKD), also known as diabetic nephropathy, is the leading cause of renal impairment and end-stage renal disease. Patients with diabetes are at risk for DKD because of poor control of their blood glucose, as well as nonmodifiable risk factors including age, ethnicity, and genetics. This genome-wide association study (GWAS) was conducted for the first time in the Emirati population to investigate possible genetic factors associated with the development and progression of DKD. We included data on 7,921,925 single nucleotide polymorphism (SNPs) in 258 cases of type 2 diabetes mellitus (T2DM) who developed DKD and 938 control subjects with T2DM who did not develop DKD. GWAS suggestive results (P < 1 × 10-5) were further replicated using summary statistics from three cohorts with T2DM-induced DKD (Bio Bank Japan data, UK Biobank, and FinnGen Project data) and T1DM-induced DKD (UK-ROI cohort data from Belfast, UK). When conducting a multiple linear regression model for gene-set analyses, the CNR2 gene demonstrated genome-wide significance at 1.46 × 10-6. SNPs in CNR2 gene, encodes cannabinoid receptor 2 or CB2, were replicated in Japanese samples with the leading SNP rs2501391 showing a Pcombined = 9.3 × 10-7, and odds ratio = 0.67 in association with DKD associated with T2DM, but not with T1DM, without any significant association with T2DM itself. The allele frequencies of our cohort and those of the replication cohorts were in most cases markedly different. In addition, we replicated the association between rs1564939 in the GLRA3 gene and DKD in T2DM (P = 0.016, odds ratio = 0.54 per allele C). Our findings suggest evidence that cannabinoid signalling may be involved in the development of DKD through CB2, which is expressed in different kidney regions and known to be involved in insulin resistance, inflammation, and the development of kidney fibrosis.

Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: A review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

GENETIC VARIANTS AND SERUM PROFILES OF CYTOKINES IN COVID-19 SEVERITY.

ABSTRACT: Background: 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. Methods: This cross-sectional study recruited 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 from six collection sites across the United Arab Emirates. Medical files were accessed to retrieve clinical data. Blood samples were collected from all participants. Patients were divided into two clinical groups, noncritical (n = 453) and critical (n = 193), according to World Health Organization classification guidelines for COVID-19 patients. Cytokine analyses were conducted on serum of a subset of the cohort, specifically on 426 participants (noncritical, 264; critical, 162). Candidate gene analyses of 33 cytokine-related genes (2,836 variants) were extracted from a genome-wide association study to identify genetic variants with pleiotropic effects on a specific cytokine and the severity of COVID-19 disease. Results: Age, body mass index (BMI), and pre-existing medical conditions were found to be significant risk factors that contribute to COVID-19 disease severity. After correcting for age, sex, and BMI, IP-10 ( P < 0.001), IFN ( P = 0.001), IL-6 ( P < 0.001), and CXCL-16 ( P < 0.001) serum levels were significantly higher among critical COVID-19 cases, when compared with noncritically ill patients. To investigate if the genetic variants involved in the serum cytokine levels are associated with COVID-19 severity, we studied several genes. Single nucleotide polymorphisms in IL6 (rs1554606; odd ratio (OR) G = 0.67 [0.66, 0.68]; P = 0.017), IFNG (rs2069718; OR G = 0.63 [0.62, 0.64]; P = 0.001), MIP (rs799187; OR A = 1.69 [1.66, 1.72]; P = 0.034), and CXCL16 (rs8071286; OR A = 1.42 [1.41, 1.44]; P = 0.018) were found to be associated with critically ill patients. Polymorphisms in the CXCL10 , CCL2 , IL1 , CCL7 , and TNF genes were not associated with the COVID-19 critical phenotype. The genotypes of IL-6 (gene, IL6 [7p15.3]) and CXCL-16 (gene, CXCL16 [17p13.2]) were significantly associated with the serum levels of the respective cytokine in critical cases of COVID-19. Conclusion: Data obtained from measuring cytokine levels and genetic variant analyses suggest that IL-6 and CXCL-16 could potentially be used as potential biomarkers for monitoring disease progression of COVID-19 patients. The findings in this study suggest that specific cytokine gene variants correlate with serum levels of the specific cytokine. These genetic variants could be of assistance in the early identification of high-risk patients on admission to the clinic to improve the management of COVID-19 patients and other infectious diseases.

Angiogenesis goes computational - The future way forward to discover new angiogenic targets?

Multi-omics technologies are being increasingly utilized in angiogenesis research. Yet, computational methods have not been widely used for angiogenic target discovery and prioritization in this field, partly because (wet-lab) vascular biologists are insufficiently familiar with computational biology tools and the opportunities they may offer. With this review, written for vascular biologists who lack expertise in computational methods, we aspire to break boundaries between both fields and to illustrate the potential of these tools for future angiogenic target discovery. We provide a comprehensive survey of currently available computational approaches that may be useful in prioritizing candidate genes, predicting associated mechanisms, and identifying their specificity to endothelial cell subtypes. We specifically highlight tools that use flexible, machine learning frameworks for large-scale data integration and gene prioritization. For each purpose-oriented category of tools, we describe underlying conceptual principles, highlight interesting applications and discuss limitations. Finally, we will discuss challenges and recommend some guidelines which can help to optimize the process of accurate target discovery.

Genomic epidemiology and emergence of SARS-CoV-2 variants of concern in the United Arab Emirates.

Since the declaration of SARS-CoV-2 outbreak as a pandemic, the United Arab Emirates (UAE) public health authorities have adopted strict measures to reduce transmission as early as March 2020. As a result of these measures, flight suspension, nationwide RT-PCR and surveillance of viral sequences were extensively implemented. This study aims to characterize the epidemiology, transmission pattern, and emergence of variants of concerns (VOCs) and variants of interests (VOIs) of SARS-CoV-2 in the UAE, followed by the investigation of mutations associated with hospitalized cases. A total of 1274 samples were collected and sequenced from all seven emirates between the period of 25 April 2020 to 15 February 2021. Phylogenetic analysis demonstrated multiple introductions of SARS-CoV-2 into the UAE in the early pandemic, followed by a local spread of root clades (A, B, B.1 and B.1.1). As the international flight resumed, the frequencies of VOCs surged indicating the January peak of positive cases. We observed that the hospitalized cases were significantly associated with the presence of B.1.1.7 (p < 0.001), B.1.351 (p < 0.001) and A.23.1 (p = 0.009). Deceased cases are more likely to occur in the presence of B.1.351 (p < 0.001) and A.23.1 (p = 0.022). Logistic and ridge regression showed that 51 mutations are significantly associated with hospitalized cases with the highest proportion originated from S and ORF1a genes (31% and 29% respectively). Our study provides an epidemiological insight of the emergence of VOCs and VOIs following the borders reopening and worldwide travels. It provides reassurance that hospitalization is markedly more associated with the presence of VOCs. This study can contribute to understand the global transmission of SARS-CoV-2 variants.

Immune response to SARS-CoV-2 variants: A focus on severity, susceptibility, and preexisting immunity.

The 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. Since it first emerged, several variants of SARS-CoV-2 have been circulating worldwide. Variants that have the potential to elude natural or vaccine-mediated immunity are variants of concern. This review focuses on the main host factors that may explain the immune responses to SARS-CoV-2 and its variants in the context of susceptibility, severity, and preexisting immunity.

Genetic Studies of Metabolic Syndrome in Arab Populations: A Systematic Review and Meta-Analysis.

Background: The metabolic syndrome (MetS) is prevalent in Arabian populations. Several small-scale studies have been performed to investigate the genetic basis of MetS. This systematic review and meta-analysis aimed to examine whether candidate gene polymorphisms are associated with MetS susceptibility among ethnic groups of the Arabian world and to suggest possible directions for future research regarding genetic markers and MetS. Methods: A search was conducted for peer-reviewed articles that examined the genetic association of MetS in Arabian populations in the following databases: Medline, Embase, Scopus, Direct Science, Web of Science, ProQuest, and Google Scholar until March 31, 2021. Articles were eligible if they were case-control studies, which investigated MetS as a dichotomous outcome (MetS vs no MetS). To assess the quality of the studies, the Q-Genie tool (Quality of Genetic Association Studies) was used. A non-central chi2 (random-effect) distribution was used to determine the heterogeneity (H) of Q and I (Galassi et al., The American journal of medicine, 2006, 119, 812-819) statistics. Results: Our search strategy identified 36 studies that met our inclusion criteria. In most cases, studies were excluded due to a lack of statistical information such as odds ratios, confidence intervals, and p-values. According to the Q-Genie tool, 12 studies scored poorly (a score of≤35), 13 studies scored moderately ( >35 and≤45), and 12 studies had good quality ( >45 or higher). The most frequently studied genes were FTO and VDR (both included in four studies). Three SNPs indicated increased risk for MetS after calculating the pooled odds ratios: FTO-rs9939609 (odds ratio 1.49, 95% CI: 0.96-2.32); LEP-rs7799039 (odds ratio 1.85, 95% CI: 1.37-2.5); and SERPINA12-rs2236242 (odds ratio 1.65, 95% CI: 1.21-2.24). Meta-analysis studies showed no significant heterogeneity. Conclusion: There were many sources of heterogeneity in the study settings. Most of the studies had low to moderate quality because of sample size and power issues, not considering all potential sources of bias, and not providing details about genotyping methods and results. As most studies were small-scale, aimed to replicate findings from other populations, we did not find any unique genetic association between MetS and Arabian populations.

Genome-wide association study of hospitalized COVID-19 patients in the United Arab Emirates.

BACKGROUND: 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. Hospitalized participants were COVID-19 patients that developed acute respiratory distress syndrome (ARDS), pneumonia or progression to respiratory failure that required supplemental oxygen therapy or mechanical ventilation support or had severe complications such as septic shock or multi-organ failure. We conducted a trans-ancestry meta-analysis GWAS of European (n=302), American (n=102), South Asian (n=99), and East Asian (n=107) ancestry populations. We also carried out comprehensive post-GWAS analysis, including enrichment of SNP associations in tissues and cell-types, expression quantitative trait loci and differential expression analysis. FINDINGS: Eight genes demonstrated a strong association signal: VWA8 gene in locus 13p14·11 (SNP rs10507497; p=9·54 x10-7), PDE8B gene in locus 5q13·3 (SNP rs7715119; p=2·19 x10-6), CTSC gene in locus 11q14·2 (rs72953026; p=2·38 x10-6), THSD7B gene in locus 2q22·1 (rs7605851; p=3·07x10-6), STK39 gene in locus 2q24·3 (rs7595310; p=4·55 x10-6), FBXO34 gene in locus 14q22·3 (rs10140801; p=8·26 x10-6), RPL6P27 gene in locus 18p11·31 (rs11659676; p=8·88 x10-6), and METTL21C gene in locus 13q33·1 (rs599976; p=8·95 x10-6). The genes are expressed in the lung, associated to tumour progression, emphysema, airway obstruction, and surface tension within the lung, as well as an association to T-cell-mediated inflammation and the production of inflammatory cytokines. INTERPRETATION: We have discovered eight highly plausible genetic association with hospitalized cases in COVID-19. Further studies must be conducted on worldwide population genetics to facilitate the development of population specific therapeutics to mitigate this worldwide challenge. FUNDING: This review was commissioned as part of a project to study the host cell receptors of coronaviruses funded by Khalifa University's CPRA grant (Reference number 2020-004).

Gut Microbiota Interplay With COVID-19 Reveals Links to Host Lipid Metabolism Among Middle Eastern Populations.

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. The gut microbiota composition of the SARS-CoV-2-infected individuals showed an increase in anti-inflammatory bacteria such as Faecalibacterium (p-value = 1.72 × 10-6) and Bacteroides (p-value = 5.67 × 10-8). We also revealed a higher relative abundance of the highly beneficial butyrate producers such as Anaerostipes (p-value = 1.75 × 10-230), Lachnospiraceae (p-value = 7.14 × 10-65), and Blautia (p-value = 9.22 × 10-18) in the SARS-CoV-2-infected group in comparison to the control group. Moreover, phylogenetic investigation of communities by reconstructing unobserved state (PICRUSt) functional prediction analysis of the 16S rRNA gene abundance data showed substantial differences in the enrichment of metabolic pathways such as lipid, amino acid, carbohydrate, and xenobiotic metabolism, in comparison between both groups. We discovered an enrichment of linoleic acid, ether lipid, glycerolipid, and glycerophospholipid metabolism in the SARS-CoV-2-infected group, suggesting a link to SARS-CoV-2 entry and replication in host cells. We estimate the major contributing genera to the four pathways to be Parabacteroides, Streptococcus, Dorea, and Blautia, respectively. The identified differences provide a new insight to enrich our understanding of SARS-CoV-2-related changes in gut microbiota, their metabolic capabilities, and potential screening biomarkers linked to COVID-19 disease severity.

Impact of Endometriosis in Women of Arab Ancestry on: Health-Related Quality of Life, Work Productivity, and Diagnostic Delay.

Introduction: Endometriosis has a negative effect on health-related quality of life (HRQoL), wellbeing and daily functioning. Endometriosis is an under-researched condition within non-western populations. Cultural representations are needed to understand the relative roles of societal norms, traditional factors, and religious sensitivities on the impact of endometriosis on HRQoL in various populations. In particular, there is a lack of emphasis placed in understanding the association of HRQoL on endometriosis in Arab women. Method: In this prospective case-control study, 2,610 Arab ancestry women in the United Arab Emirates were recruited to investigate the impact of endometriosis on HRQoL, diagnostic delay, psychological co-morbidities, work productivity, and physical activity. Participants completed the following standardized, validated questionnaires: Short Form-36 version 2 questionnaire, the World Endometriosis Research Foundation EPHect minimum clinical questionnaire version, and Work Productivity and Activity Impairment questionnaire. Translations to the Arabic language, validated using the forward-backward translation method, of the questionnaires were utilized. Results: HRQoL scores were significantly impaired in women with endometriosis, as demonstrated in the Physical Composite Scores and Mental Composite Scores in the symptomatic control group (p = 0.001; p = 0.003, respectively) and the asymptomatic control group (p < 0.001; p < 0.001, respectively). Susceptibility and severity of multiple pain syndromes and infertility in women with endometriosis was the main indicator of lower HRQoL. Anxiety (p = 0.007) and depression (p = 0.005) were significantly associated with endometriosis, in comparison to symptomatic controls. The average diagnostic delay was 11.61 years, however single women experience 15.81 years of diagnosis delay, with approximately 18% (n = 15) of the single women experiencing more than a 20-year delay in diagnosis. The intensity of physical activity was not associated with endometriosis, when compared to symptomatic (p = 0.405) or asymptomatic controls (p = 0.144). Conclusion: For the first time, we provide evidence from a combined hospital, clinic, and population-based study that Arab women with endometriosis experience significant impacts on HRQoL, substantial diagnostic delay after the onset of symptoms, significant association to psychological disorders (anxiety and depression), and a negative impact on work productivity. Future research must focus on understanding the personal and culturally centered beliefs of Arab women to ensure a positive HRQoL trajectory by improving diagnosis and management strategies.

Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 among UAE Residents.

Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were compiled in patients admitted to a major hospital in the United Arab Emirates between April 2020 and January 2021. We identified 12 single-nucleotide polymorphisms associated with the critical COVID-19 condition: rs59241277, rs113574864, rs182901986, rs60349934, and rs113876500; rs4944076, rs4944997, rs4944998, rs4944979, and rs10898210; and rs11574018 and rs11574024. We report significant associations between genetic determinants of vitamin D metabolism and COVID-19 severity in the UAE population. Further research needed to clarify the mechanism of action against viral infection in vitamin D deficiency. These variants could be used with vaccination to manage the spread of SARS-CoV-2 and could be particularly valuable in populations in which vitamin D deficiency is common.

Evolution, Ecology, and Zoonotic Transmission of Betacoronaviruses: A Review.

Coronavirus 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 via an intermediate host. This has a range of effects from annual infections that are mild to full-blown pandemics. This review compares the zoonotic potential and relationship between MERS, SARS-CoV, and SARS-CoV-2. The role of bats as possible host species and possible intermediate hosts including pangolins, civets, mink, birds, and other mammals are discussed with reference to mutations of the viral genome affecting zoonosis. Ecological, social, cultural, and environmental factors that may play a role in zoonotic transmission are considered with reference to SARS-CoV, MERS, and SARS-CoV-2 and possible future zoonotic events.

Allelic Variants Within the ABO Blood Group Phenotype Confer Protection Against Critical COVID-19 Hospital Presentation.

Introduction: Coronavirus disease 2019 (COVID-19) disease severity differs widely due to numerous factors including ABO gene-derived susceptibility or resistance. The objective of this study was to investigate the association of the ABO blood group and genetic variations of the ABO gene with COVID-19 severity in a heterogeneous hospital population sample from the United Arab Emirates, with the use of an epidemiological and candidate gene approach from a genome-wide association study (GWAS). Methods: In this cross-sectional study, a total of 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited from multiple hospitals and population-based (quarantine camps) recruitment sites from March 2020 to February 2021. The participants were divided into two groups based on the severity of COVID-19: noncritical (n = 453) and critical [intensive care unit (ICU) patients] (n = 193), as per the COVID-19 Reporting and Data System (CO-RADS) classification. The multivariate logistic regression analysis demonstrated the association of ABO blood type as well as circulating anti-A antibodies and anti-B antibodies as well as A and B antigens, in association with critical COVID-19 hospital presentation. A candidate gene analysis approach was conducted from a GWAS where we examined 240 single nucleotide polymorphisms (SNPs) (position in chr9: 136125788-136150617) in the ABO gene, in association with critical COVID-19 hospital presentation. Results: Patients with blood group O [odds ratio (OR): 0.51 (0.33, 0.79); p = 0.003] were less likely to develop critical COVID-19 symptoms. Eight alleles have been identified to be associated with a protective effect of blood group O in ABO 3'untranslated region (UTR): rs199969472 (p = 0.0052), rs34266669 (p = 0.0052), rs76700116 (p = 0.0052), rs7849280 (p = 0.0052), rs34039247 (p = 0.0104), rs10901251 (p = 0.0165), rs9411475 (p = 0.0377), and rs13291798 (p = 0.0377). Conclusion: Our findings suggest that there are novel allelic variants that link genetic variants of the ABO gene and ABO blood groups contributing to the reduced risk of critical COVID-19 disease. This study is the first study to combine genetic and serological evidence of the involvement of the ABO blood groups and the ABO gene allelic associations with COVID-19 severity within the Middle Eastern population.

Prevalence of Common Gynecological Conditions in the Middle East: Systematic Review and Meta-Analysis.

Introduction: High prevalence of gynecological conditions in women of Middle Eastern origin is reported, likely due to regional risk factors and mediators. The objective of this systematic review and meta-analysis is to investigate the prevalence of polycystic ovary syndrome (PCOS), endometriosis, uterine fibroids, and adenomyosis in women of Middle Eastern origin. Methods: MEDLINE, EMBASE, PsycINFO, Global Health, and Google Scholar databases were searched from database inception until 14 February 2021 to identify relevant studies. Peer-reviewed research articles that reported the prevalence of PCOS, endometriosis, uterine fibroids, and adenomyosis in the Middle Eastern population were written in English or Arabic. The primary outcome was the estimated pooled prevalence of PCOS, endometriosis, uterine fibroids, and adenomyosis in the Middle Eastern populations. The secondary outcome was to assess the evidence in the data for the presence of heterogeneity, by conducting subtype-pooled analysis of prevalence estimates of the conditions. Total weighted prevalence was calculated via Freeman-Tukey arcsine transformation and heterogeneity through the I 2 statistic. Quality control was performed using GRADE criteria. Results: A total of 47 studies, 26 on PCOS, 12 on endometriosis, eight on uterine fibroids, and seven on adenomyosis, were included. The pooled prevalence of PCOS diagnosed according to the NIH criteria was 8.9% (95% CI: 6.5-11.7; prevalence range: 4.0-27.6%), with a higher prevalence from the Gulf Arab states (18.8%, 95% CI: 9.5-30.3; range: 12.1-27.6%). According to the Rotterdam criteria, the pooled prevalence of PCOS was 11.9% (95% CI: 7.1-17.7; range: 3.4-19.9%) with studies limited to the Persian and Levant regions. Endometriosis was diagnosed in 12.9% (95% CI: 4.2-25.4; range: 4.2-21.0%) of women undergoing laparoscopy, for any indication. Uterine fibroid and adenomyosis prevalence of women was 30.6% (95% CI: 24.9-36.7; range: 18.5-42.6%) and 30.8% (95% CI: 27.1-34.6, range: 25.6-37.7%), respectively. Heterogeneity was present between studies due to statistical and methodological inconsistencies between studies, and quality of evidence was low due to sample size and unrepresentative participant selection. Conclusion: This is the first review that has reported the prevalence of gynecological diseases in the Middle Eastern population, suggesting that gynecological morbidity is a public health concern. Due to the health disparities in women, further research is required to understand the relative roles of environmental and genetic factors in the region to serve as a benchmark for evaluation and comparative purposes with other populations.