Habiba Alsafar’s research while affiliated with Emirates Aviation University and other places

Background In the pursuit of global health security, continuous monitoring of vaccine effectiveness across various viral strains emerges as a crucial imperative. The emergence of SARS-CoV-2 major variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron, has added complexity to the COVID-19 vaccination landscape. Objectives To assess illness severity, evaluate vaccine efficacy across varying doses and types, and determine effectiveness against major VOCs within the population. Methods This retrospective cohort study, conducted in Abu Dhabi, United Arab Emirates, focuses on a cohort of 44,073 SARS-CoV-2 positive cases from February 2021 to May 2022, dominated by the Delta and Omicron variants. The study employed a nested case-control design, analyzing hospital admissions for confirmed SARS-CoV-2 infection. Results Vaccine effectiveness was higher among heterologus-boosted individuals at 87% (95% CI:79%-93%) compared to homologus-boosted individuals at 59% (95% CI: 48%-68%) and fully vaccinated, non-boosted adults at 53% (95% CI: 46%-59%). These findings highlight the importance of heterologous boosting, particularly against rapidly evolving viral variants, offering valuable insights for refining pandemic response strategies. Conclusion The study underscores the critical need for ongoing assessment and adaptation of vaccination strategies to the evolving viral landscape.

Control and prevention of environmental pollution have emerged as paramount global concerns. Anthropogenic activities, such as industrial discharges, agricultural runoff, and improper waste disposal, introduce a wide range of contaminants into various ecosystems. These pollutants encompass organic and inorganic compounds, particulates, microorganisms, and disinfection by-products, posing severe threats to human health, ecosystems, and the environment. Effective monitoring methods are indispensable for assessing environmental quality, identifying pollution sources, and implementing remedial measures. This paper suggests that the development and utilization of highly advanced analytical tools are both essential for the analysis of contaminants in water samples, presenting a foundational hypothesis for the review. This paper comprehensively reviews the development and utilization of highly advanced analytical tools which is mandatory for the analysis of contaminants in water samples. Depending on the specific pollutants being studied, the choice of analytical methods widely varies. It also reveals insights into the diverse applications and effectiveness of these methods in assessing water quality and contaminant levels. By emphasizing the critical role of the reviewed monitoring methods, this review seeks to deepen the understanding of pollution challenges and inspire innovative monitoring solutions that contribute to a cleaner and more sustainable global environment.•Urgent global concerns: control and prevention of pollution from diverse sources. •Varied contaminants, diverse methods: comprehensive review of analytical tools. •Inspiring a sustainable future: innovative monitoring for a cleaner environment.

Introduction The COVID-19 pandemic represented one of the most significant challenges to researchers and healthcare providers. Several factors determine the disease severity, whereas none alone can explain the tremendous variability. The Single nucleotide variants (SNVs) in angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease type-2 (TMPRSS2) genes affect the virus entry and are considered possible risk factors for COVID-19. Methods We compiled a panel of gene variants from both genes and used in-silico analysis to predict their significance. We performed biological validation to assess their capacity to alter the ACE2 interaction with the virus spike protein. Subsequently, we conducted a retrospective comparative genome analysis on those variants in the Emirati patients with different disease severity (total of 96) along with 69 healthy control subjects. Results Our results showed that the Emirati population lacks the variants that were previously reported as associated with disease severity, whereas a new variant in ACE2 “Chr X:g.15584534” was associated with disease severity specifically among female patients. In-silico analysis revealed that the new variant can determine the ACE2 gene transcription. Several cytokines (GM-CSF and IL-6) and chemokines (MCP-1/CCL2, IL-8/CXCL8, and IP-10/CXCL10) were markedly increased in COVID-19 patients with a significant correlation with disease severity. The newly reported genetic variant of ACE2 showed a positive correlation with CD40L, IL-1β, IL-2, IL-15, and IL-17A in COVID-19 patients. Conclusion Whereas COVID-19 represents now a past pandemic, our study underscores the importance of genetic factors specific to a population, which can influence both the susceptibility to viral infections and the level of severity; subsequently expected required preparedness in different areas of the world.

Surveillance methods of circulating antibiotic resistance genes (ARGs) are of utmost importance in order to tackle what has been described as one of the greatest threats to humanity in the 21st century. In order to be effective, these methods have to be accurate, quickly deployable, and scalable. In this study, we compare metagenomic shotgun sequencing (TruSeq DNA sequencing) of wastewater samples with a state-of-the-art PCR-based method (Resistomap HT-qPCR) on four wastewater samples that were taken from hospital, industrial, urban and rural areas. ARGs that confer resistance to 11 antibiotic classes have been identified in these wastewater samples using both methods, with the most abundant observed classes of ARGs conferring resistance to aminoglycoside, multidrug-resistance (MDR), macrolide-lincosamide-streptogramin B (MLSB), tetracycline and beta-lactams. In comparing the methods, we observed a strong correlation of relative abundance of ARGs obtained by the two tested methods for the majority of antibiotic classes. Finally, we investigated the source of discrepancies in the results obtained by the two methods. This analysis revealed that false negatives were more likely to occur in qPCR due to mutated primer target sites, whereas ARGs with incomplete or low coverage were not detected by the sequencing method due to the parameters set in the bioinformatics pipeline. Indeed, despite the good correlation between the methods, each has its advantages and disadvantages which are also discussed here. By using both methods together, a more robust ARG surveillance program can be established. Overall, the work described here can aid wastewater treatment plants that plan on implementing an ARG surveillance program.

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. The patient was admitted with no respiratory symptoms, showed a SARS-CoV-2 PCR positive test on the second day of admission, started developing progressive lung consolidation within three days of hospitalization, and was moved from non-invasive to mechanical ventilation within 12 days of hospitalization. Impaired production of type I IFN was detected in patient PBMCs treated with poly(I:C), at both mRNA and protein levels. Whole exome sequencing revealed three mutations across type I IFN production pathway, which were predicted to be loss-of-function (pLOF). The three mutations were predicted to predispose to severe viral infections: monoallelic R488X TLR3, monoallelic His684Arg TLR3, and biallelic Val363Met IRF3. Functional analysis confirmed that all these mutations dysregulated the type I IFN pathway. Evaluation of TLR3 and IRF3 IFN-β1 luciferase reporter activity showed a hypomorphic suppression of function. TOPO TA cloning was used to ascertain the positioning of both TLR3 variants, indicating that both variants were on the same allele. We have described a unique complex IEI patient with multiple mutations, particularly along type I IFN production pathway.

The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals. A cohort of 570 unrelated healthy citizens of the UAE volunteered to provide samples for Whole Genome Sequencing and Whole Exome Sequencing. The definition of the HLA alleles was achieved through the application of the bioinformatics tools, HLA-LA and xHLA. Subsequently, the findings from this study were compared with other local and international datasets. A broad range of HLA alleles in the UAE population, of which some were previously unreported, was identified. A comparison with other populations confirmed the current population’s unique intertwined genetic heritage while highlighting similarities with populations from the Middle East region. Some disease-associated HLA alleles were detected at a frequency of > 5%, such as HLA-B*51:01, HLA-DRB1*03:01, HLA-DRB1*15:01, and HLA-DQB1*02:01. The increase in allele homozygosity, especially for HLA class I genes, was identified in samples with a higher level of genome-wide homozygosity. This highlights a possible effect of consanguinity on the HLA homozygosity. The HLA allele distribution in the UAE population showcases a unique profile, underscoring the need for tailored databases for traditional activities such as unrelated transplant matching and for newer initiatives in precision medicine based on specific populations. This research is part of a concerted effort to improve the knowledge base, particularly in the fields of transplant medicine and investigating disease associations as well as in understanding human migration patterns within the Arabian Peninsula and surrounding regions.

Background Statins are the most prescribed lipid-lowering drugs worldwide. The associated adverse events, especially muscle symptoms, have been frequently reported despite their perceived safety. Three pharmacogenes, the solute carrier organic anion transporter family member 1B1 (SLCO1B1), ATP-binding cassette subfamily G member 2 (ABCG2), and cytochrome P450 9C9 (CYP2C9) are suggested as safety biomarkers for statins. The Clinical Pharmacogenomic Implementation Consortium (CPIC) issued clinical guidelines for statin use based on these three genes. Objectives The present study aimed to examine variants in these pharmacogenes to predict the safety of statin use among the Emirati population. Methods Analyzing 242 whole exome sequencing data at the three genes enabled the determination of the frequencies of the single nucleotide polymorphisms (SNPs), annotating the haplotypes and the predicted functions of their proteins. Results In our cohort, 29.8% and 5.4% had SLCO1B1 decreased and poor function, respectively. The high frequency warns of the possibility of significant side effects of some statins and the importance of pharmacogenomic testing. We found a low frequency (6%) of the ABCG2:rs2231142 variant, which indicates the low probability of Emirati patients being recommended against higher rosuvastatin doses compared with other populations with higher frequencies of this variant. In contrast, we found high frequencies of the functionally impaired CYP2C9 alleles, which makes fluvastatin a less favorable choice. Conclusion Among the sparse studies available, the present one demonstrates all SLCO1B1 and CYP2C9 function-impairing alleles among Emiratis. We highlighted how population-specific pharmacogenomic data can predict safer choices of statins, especially in understudied populations.