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Coronavirus disease 2019 (COVID-19) is a fatal pandemic viral disease caused by the severe acute respiratory syndrome corona virus type-2 (SARS-CoV-2). The aim of this study is to observe the associations of IL-6, SARS-COV-2 viral load (RNAemia), IL- 6 gene polymorphism and lymphocytes and monocytes in peripheral blood with disease severity in COVID-19 patients. This study was carried out from March 2021 to January 2022. RT-PCR positive 84 COVID-19 patients and 28 healthy subjects were enrolled. Blood was collected to detect SARS-COV-2 viral RNA (RNAemia) by rRT-PCR, serum IL-6 level by chemiluminescence method, SNPs of IL-6 by SSP-PCR, immunophenotyping of lymphocytes and monocyte by flow cytometry. Serum IL-6 level (pg/ml) was considerably high among critical patients (102.02 +/- 149.7) compared to severe (67.20 +/- 129.5) and moderate patients (47.04 +/- 106.5) and healthy controls (3.5 +/- 1.8). Serum SARS-CoV-2 nucleic acid positive cases detected mostly in critical patients (39.28%) and was correlated with extremely high IL-6 level and high mortality (R =.912, P < 0.001). Correlation between IL-6 and monocyte was statistically significant with disease severity (severe group, p < 0.001, and 0.867*** and critical group p < 0.001 and 0.887***). In healthy controls, moderate, severe and critically ill COVID-19 patients, IL-6 174G/C (rs 1800795) GG genotype was 82.14%, 89.20%, 67.85% and 53.57% respectively. CC and GC genotype had strong association with severity of COVID-19 when compared with GG genotype. Significant statistical difference found in genotypes between critical and moderate groups (p < 0.001, OR-10.316, CI-3.22-23.86), where CC genotype was associated with COVID-19 severity and mortality. The absolute count of T cell, B cell, NK cell, CD4+ T cells and CD8+ T cells were significantly decreased in critical group compared to healthy, moderate and severe group (P < 0.001). Exhaustion marker CD94/NKG2A was increased on NK cells and CD8+ cytotoxic T cell among critical and severe group. Absolute count of monocyte was significantly increased in critical group (P < 0.001). Serum IL-6, IL-6 174 G/C gene and SARS-CoV-2 RNAaemia can be used in clinical practice for risk assessment;T cell subsets and monocyte as biomarkers for monitoring COVID-19 severity. Monoclonal antibody targeting IL-6 receptor and NKG2A for therapeutics may prevent disease progression and decrease morbidity and mortality.Copyright © 2023 Elsevier Inc.
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Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.
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Background/Objectives: Chemosensory dysfunction is a hallmark of SARS-CoV-2 infection;nevertheless, the genetic factors predisposing to long-term smell and taste loss are still unknown. This study aims to identify candidate genes possibly involved in persistent smell/taste loss through Whole Genome Sequencing (WGS) analysis of a large cohort of 130 fully characterised Italian individuals, previously diagnosed with COVID-19. Method(s): DNA of all analysed patients was used to perform WGS analysis, and a detailed personal anamnesis was collected. Moreover, orthonasal function was assessed through the extended Sniffin' Sticks test, retronasal function was tested with 20 powdered tasteless aromas, and taste was determined with validated Taste Strips. Self-reported smell and taste alterations were assessed via Visual Analog Scales plus questionnaires. Result(s): The clinical evaluation allowed to classify the patients in two groups: 88 cases affected by persistent smell dysfunction (median age, 49) and 42 controls (median age, 51). Among cases, 26.1% (n = 23) were functionally anosmic and 73.9% (n = 65) were hyposmic. Within cases, 77 underwent the taste strip test: 53.2% (n = 41) presented hypogeusia and 46.8% (n = 36) were normogeusic. Preliminary WGS results on a first subset of 76 samples confirmed the important role of UGT2A1 gene, previously described as involved in smell loss. Interestingly, we identified a nonsense variant (rs111696697, MAF 0.046) significantly associated with anosmia in males (p-value: 0.0183). Conclusion(s): Here, for the first time a large cohort of patients, fully characterised through a comprehensive psychophysical evaluation of smell and taste, have been analysed to better define the genetic bases of COVID-19-related persistent chemosensory dysfunction.
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The traditional de novo drug discovery is time consuming, costly and in some instances the drugs will fail to treat the disease which result in a huge loss to the organization. Drug repurposing is an alternative drug discovery process to overcome the limitations of the De novo drug discovery process. Ithelps for the identification of drugs to the rare diseases as well as in the pandemic situationwithin short span of time in a cost-effective way. The underlying principle of drug repurposing is that most of the drugs identified on a primary purpose have shown to treat other diseases also. One such example is Tocilizumab is primarily used for rheumatoid arthritis and it is repurposed to treat cancer and COVID-19. At present, nearly30% of the FDA approved drugs to treat various diseases are repurposed drugs. The drug repurposing is either drug-centric or disease centric and can be studied by using both experimental and in silico studies. The in silico repurpose drug discovery process is more efficient as it screens thousands of compounds from the diverse libraries within few days by various computational methods like Virtual screening, Docking, MD simulations,Machine Learning, Artificial Intelligence, Genome Wide Association Studies (GWAS), etc. with certain limitations.These limitationscan be addressed by effective integration of advanced technologies to identify a novel multi-purpose drug.Copyright © 2023, Association of Biotechnology and Pharmacy. All rights reserved.
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Background/Objectives: One of the most remarkable features of SARS-CoV-2 infection is that a large proportion of individuals are asymptomatic while others experience progressive, even lifethreatening acute respiratory distress syndrome, and some suffer from prolonged symptoms (long COVID). The contribution of host genetics to susceptibility and severity of infectious disease is well-documented, and include rare monogenic inborn errors of immunity as well as common genetic variation. Studies on genetic risk factors for long COVID have not yet been published. Method(s): We compared long COVID (1534) to COVID-19 patients (96,692) and population controls (800,353) using both questionnaire and EHR- based studies. First meta-analysis of 11 GWAS studies from 8 countries did not show genome-wide significant associations. Result(s): Testing 24 variants earlier associated to COVID-19 susceptibility or severity by COVID-19 Host Genetics Initiative showed genetic variation in rs505922, an intronic variant in ABO blood group gene, to be associated with long COVID compared to population controls (OR = 1.16, 95% CI: 1.07-1.27, p = 0.033). (Within-COVID analysis gave similar OR, but was not significant after conservative Bonferroni correction (OR = 1.17, 95% CI: 1.06-1.30, p = 092)). Conclusion(s): The first data freeze of the Long COVID Host Genetics Initiative suggests that the O blood group is associated with a 14% reduced risk for long COVID. The following data freezes with growing sample sizes will possibly elucidate long COVID pathophysiology and pave the way for possible treatments for long lasting COVID symptoms.
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A new coronavirus infection (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out at the end of 2019 in Wuhan (China). The disease has become a global pandemic and claimed more than 6 million lives after spreading rapidly around the world. Issues related to the complicated course of COVID-19 mechanisms continue to be the subject of active study. It is known that morbidity and mortality increase dramatically with increasing age and concomitant diseases, including obesity, diabetes, cancer, and cardiovascular diseases. Although most infected people recover, even young and otherwise healthy patients can get sick with this disease. In this regard, an urgent task is to search for specific genetic factors that can explain the predisposition of people to infection and the development of a severe COVID-19 form. Human genetic determinants can provide the scientific basis for disease prediction and the development of personalized therapies to counteract the epidemic. In addition, cases of repeated infection with SARS-CoV-2 are increasingly being registered, which occurs 1–6 months after initial infection on average and depends on the virus genome structure. Studies conducted on sequencing viral genomes have shown that some patients were re-infected with the same strain of coronavirus, while others were different. This, in turn, causes researchers concerns about the effectiveness of immunity after infection and vaccine reliability. The genetic characteristics of a person and a virus commonly determine the tendency for reinfection. It is difficult to determine the true COVID-19 reinfection prevalence, which is explained by the low detectability of asymptomatic reinfection and the fact that many patients with a mild course of the disease were not tested at an early stage of the pandemic. Therefore, the true prevalence of reinfection with COVID-19 does not reflect the current reality. There are many more cases of reinfection than are described in the literature. In this regard, the true contribution of a virus' genetic features to reinfection of COVID-19 can be determined only after population studies, and when developing immunization programs against a COVID-19, it is necessary to take into account the prevalence of reinfection in the population. The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.
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Background/Objectives: Despite intensive research of the novel coronavirus SARS-CoV-2 and COVID-2019 caused by it, factors affecting the severity of the disease remains poorly understood. Clinical manifestations of COVID-2019 may vary from asymptomatic form to pneumonia, acute respiratory distress syndrome (ARDS) and multiorgan failure. Features of individual genetic landscape of patients can play an important role in development of the pathological process of COVID-19. In this regard the purpose of this study was to investigate the influence of polymorphic variants in genes (ADD1, CAT, IL17F, IL23R, NOS3, IFNL3, IL6, F2, F13A1, ITGB3, HIF1A, MMP12, VEGFA), associated with cardiovascular, respiratory and autoimmune pathologies, on the severity of COVID-19 and post-COVID syndrome in patients from Russia. Method(s): The study included 200 patients recovered from COVID-19. Two groups of patients were formed in accordance with clinical manifestations: with mild and moderate forms of the disease. The polymorphic variants were analysed with real-time PCR using commercial kits (Syntol). Result(s): 13 SNPs (rs4961;rs1001179;rs612242;rs11209026;rs2070744;rs8099917;rs1800795;rs1799963;rs5985;rs5918;rs11549465;rs652438;rs699947) were genotyped and comparative analysis of allele frequency distribution was carried out in two groups of patients recovered from COVID-2019. Conclusion(s): Identification of polymorphic variants in genome associated with severity of pathological processes in patients infected with SARS-CoV-2 can contribute to the identification of individuals with an increased risk of severe infection process and can also serve as a basis for developing personalized therapeutic approaches to the treatment of post-COVID syndrome.
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Background/Objectives: The COVID-19 pandemic continues to threaten public health and burden healthcare systems worldwide. Whole SARS-CoV-2 genome sequencing has become essential for epidemiological monitoring and identification of new variants, which could represent a risk of increased transmissibility, virulence, or resistance to vaccines or treatment. In this study, we assess the performance of various target enrichment methods for whole SARS-CoV-2 sequencing. Method(s): We applied three target enrichment methods - two multiplex amplification methods and one hybridization capture - to the same set of nasopharyngeal patient samples (N = 93) in high-throughput mode. SARS-CoV-2 genome was obtained using short-read next-generation sequencing. Result(s): All three methods provided excellent breadth of coverage of SARS-CoV-2 genome (above 99%), albeit with vastly different sequencing depth (5-fold difference) and uniformity of coverage (20% difference in coefficient of variation). Poor local coverage has negative impact on variant calling in the concerned region, leading to an occasional allele drop-out (1.2% SNPs affected for one method). Conclusion(s): We discuss the performance of each target enrichment method and their potential for scaling up, in order to promote prospective programs of large-scale genomic surveillance of SARS-CoV-2 worldwide. Genomic surveillance will be crucial to overcoming the ongoing pandemic of COVID-19, despite its successive waves and continually emerging variants.
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Objective: During the COVID-19 pandemic, cancer patients had restricted access to standard of care tissue biopsy. Liquid biopsy assays using next generation sequencing technology provides a less invasive method for determining circulating tumour mutations (ctDNA) associated with targeted treatments or prognosis. As part of deploying technology to help cancer patients obtain molecular testing, a clinical program was initiated to offer liquid biopsy testing for Canadian patients with advanced or metastatic breast cancer. Method(s): Blood was drawn in two 10 mL StreckTM DNA BCTs and sent to the CAP/CLIA/DAP accredited Imagia Canexia Health laboratory for testing using the clinically validated Follow ItTM liquid biopsy assay. Plasma was isolated using a double spin protocol and plasma cell-free DNA (cfDNA) extracted using an optimized Promega Maxwell RSC method. Extracted cfDNA was amplified using the multiplex amplicon-based hotspot 30 or 38 gene panel and sequenced. An inhouse developed bioinformatics pipeline and reporting platform were used to identify pathogenic single nucleotide variants (SNVs), indels (insertions and deletions), and gene amplification. Included in the panel are genes associated with metastatic breast cancer: AKT1, BRAF, ERBB2, ESR1, KRAS, PIK3CA, TP53. Result(s): To identify biomarkers, 1214 metastatic or advanced breast cancer patient cfDNA samples were tested. There were 15 cases sent for repeat testing. We reported 48% of samples harboring pathogenic ctDNA mutations in TP53 (22%), PIK3CA (19%), ESR1 (18%), AKT1 (2%), ERBB2 (1.5%). Co-occurring variants were identified in samples with ESR1/PIK3CA as well as TP53/PIK3CA (both p-values <0.001). Interestingly, 29% of samples with mutated ESR1 harbored >= 2 ESR1 ctDNA mutations. In 56% of cases, previous molecular testing indicated the cancer subtype as hormone receptor (ER, PR) positive with/without HER2 negative status. In this specific subgroup, 49% harbored ctDNA mutations with 63% of those being PIK3CA and/or ESR1 mutations. Conclusion(s): A population of Canadian women with metastatic breast cancer were tested using a liquid biopsy gene panel during the COVID-19 pandemic for identification of biomarkers for targeted therapeutic options. Over 50% of the samples were identified as hormone positive, with greater than 60% harboring PIK3CA and ESR1 ctDNA mutations. Studies have shown that metastatic PIK3CA mutated ER-positive/HER2-negative tumors are predictive to respond to alpelisib therapy and have FDA and Health Canada approval. Additionally, ESR1 mutations are associated with acquired resistance to antiestrogen therapies, and interestingly we identified 29% of ESR1 mutated samples with multiple mutations possibly indicating resistance subclones. In future studies, longitudinal monitoring for presence of multiple targetable and resistance mutations could be utilized to predict or improve clinical management.
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Background/Objectives: Runaway inflammation is a key feature of COVID-19. NR3C1 gene encodes for glucocorticoid receptor which plays an important role in inflammation reaction. The variant rs41423247 cause increased glucocorticoid receptors sensitivity. This study aimed to investigate the impact of variants of NR3C1 gene on the course of COVID-19 pneumonia in patients with necessarily artificial lung ventilation. Method(s): The study group included 20 patients (9 women and 11 men) with diagnosis viral COVID-19 pneumonia on artificial lung ventilation at the intensive care unit. All patients underwent daily standard examinations according clinical protocols. Determination of NR3C1 gene variants was carried out by using PCRRFLP. Result(s): There were found the significant negative correlations between NR3C1 gene variants and level of SpO2 (rS = -0.601, p = 0.008), Glasgow Coma Scale score (rS = -0.523, p = 0.026). Also, it was defined a protective effect of genotype CC at risk of development acute respiratory distress syndrome in this patients (chi2 = 4.38, p = 0.037, OR = 0.05 (CI:0.01-0.66)). Conclusion(s): The investigated variant rs41423247 of the NR3C1 gene may be the genetic predictor of complicated course of COVID-19 pneumonia. .
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Background/Objectives: COVID-19 still represents a lifethreatening disease in individuals with a specific genetic background. We successfully applied a new Machine Learning method on WES data to extract a set of coding variants relevant for COVID- 19 severity. We aim to identify personalized add-on therapy. Method(s): A subset of identified variants, "actionable" by repurposed drugs, were functionally tested by in vitro and in vivo experiments. Result(s): Males with either rare loss of function variants in the TLR7 gene or L412F polymorphism in the TLR3 gene benefit from IFN-gamma, which is specifically defective in activated PBMCs, restoring innate immunity. Females heterozygous for rare variants in the ADAMTS13 gene and males with D603N homozygous polymorphism in the SELP gene benefit from Caplacizumab, which reduces vWF aggregation and thrombus formation. Males with either the low-frequency gain of function variant T201M in CYP19A1 gene or with poly-Q repeats >=23 in the AR gene benefit from Letrozole, an aromatase inhibitor, which restores normal testosterone levels, reducing inflammation and which rescues male golden hamsters from severe COVID-19. Conclusion(s): By adding these commonly used drugs to standard of care of selected patients, the rate of intubation is expected to decrease consistently, especially in patients with high penetrance rare genetic markers, mitigating the effect of the pandemic with a significant impact on the healthcare system.
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The most significant single nucleotide human leukocyte antigen genes polymorphisms and innate immunity genes associated with varying degrees of acute respiratory infection severity are considered–COVID-19 caused by the SARS-CoV-2 coronavirus. As data accumulated, it became clear that the SARS-CoV-2 virus exhibits significant regional, ethnic, and individual specificity. This is due to the population groups' genetic characteristics. This is necessary to reliably know the human genotype relationship with the COVID-19 course severity (asymptomatic, mild, moderate, severe, and extremely severe up to fatal outcomes) for more successful therapy and vaccination. At the same time, it was also known that the innate immunity system is on the first line of defense against the pathogenic penetration into the body, and the human leukocyte antigen system encodes molecules of the same name on the surface of cells that present various antigens, including viral infection pathogens, and determine the severity of the course of many diseases;therefore, these systems' genes. This approach makes it possible to assess the likelihood of a severe and extremely severe disease course in healthy and infected people, which in turn contributes to the correct therapy strategy, pharmacotherapy, and vaccination, as well as to create new antiviral therapeutic and preventive medicines. The genetically determined immune response heterogeneity to SARS-CoV-2 infection requires further study, since there is no unambiguous opinion about the leading mechanism that determines disease severity. The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.
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A problem of the novel coronavirus infection pandemic is the absence of specific biomarkers, the determination of which would make it possible to assess the likelihood of a severe disease course, development of complications, immediate and long-term consequences, and effective etiotropic (antiviral) therapy. The severity of the novel coronavirus infection depends on various factors such as the initial state of health, immune status, age, smoking status, concomitant cardiovascular diseases, and diabetes mellitus. However, a severe disease course is also observed in patients without the aforementioned risk factors. The development of the disease and its complications depends on sex and geographical identity. Angiotensin-converting enzyme 2 (ACE2), associated by gene-gene interaction with ACE, plays a main role in the pathogenesis of the penetration of severe acute respiratory syndrome-2 coronavirus into the cell. The main body of information on this problem is represented by systematic meta-analyses and results of single-center cohort studies, which offer insufficient information to unequivocally assert the associations of ACE and ACE2 gene polymorphisms with pathological changes in the circulatory system during and after a new coronavirus infection. Differences in the incidence of ACE and ACE2 alleles may explain the differences between susceptible populations and/or response to the severe coronavirus infection. The above studies were carried out on the effect of the coronavirus in the initial period of the pandemic. For a more complete molecular genetic picture of the influence of polymorphism, persons with different strains of the coronavirus must be considered. In addition, no data are available regarding the expressions of ACE and ACE2 genes in response to a coronavirus infection. Moreover, the identification of the polymorphic variants of the genes of the renin–angiotensin–aldosterone system and ACE2 associated with a high risk of developing and worsening cardiovascular diseases may be one of the promising areas for the early diagnosis and prevention of post-COVID-19 changes. Therefore, all scientific interest research is aimed at studying genetic factors, such as single nucleotide polymorphisms that affect susceptibility to infection, severity of the disease course, and development of circulatory system consequences. In general, polymorphic variants of ACE and ACE2 and their interaction will help us understand this problem and systematize knowledge for further research in this area. All rights reserved © Eco-Vector, 2022.
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Background: From the time when the first outbreak of coronavirus disease (COVID-19), only a small proportion of infected people developed a severe infection, which is usually a sequel of cytokine overproduction. Genetic variations in the genes of some cytokines can influence the transcription rate of these cytokines. Objective: The going research article tried to evaluate the link between tumor necrosis factor (TNF)-α-308 gene polymorphism and COVID-19 severity. Materials and Methods: Blood samples were obtained from 60 patients with COVID-19 and verified by reverse transcriptase polymerase chain reaction (PCR) in nasopharyngeal swabs. Patients were categorized into two categories based on the severity of the disease: severe COVID-19 included 30 patients and mild/moderate COVID-19 with 30 patients. The nucleic DNA was obtained from the whole blood, and TNF-α-308G>A polymorphism was genotyped utilizing PCR-restriction fragment length polymorphism. Results: Homozygous (GG) and heterozygous (GA) genotypes were more frequent among severe than among mild cases, although the differences were not significant. At the allelic level, the frequency of a mutant allele (A) was higher in severe than in mild cases with a noticeable distinction (odds ratio = 2.49, 95% confidence interval = 1.1-5.64, P = 0.029). Conclusion: Allele A of TNF-α-308G>A may be deemed a threat for the severity of COVID-19. © 2023 Medical Journal of Babylon.
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SUMMARY. Different genetic and immunological factors can affect the severity of Coronavirus disease 19. Angiotensin-converting enzyme 2 is a human receptor for Severe Acute Respiratory Syndrome Coro-navirus-2, and the successful interaction between the spike protein of the novel virus and Angiotensin-converting enzyme 2 is responsible for the initial and complete infection. The study aimed to evaluate the correlation between Single Nucleotide Polymorphisms of Angiotensin converting-enzyme 2, with disease severity of Coronavirus disease 19 in AL-Najaf province. The allele Specific-polymerase Chain reaction method was used for investigating Single Nucleotide polymorphisms of Angiotensin converting-enzyme 2 rs4646116 A/G in different states of Coronavirus disease 19 (COVID-19). The wild genotypes (GG) for ACE2 rs4646116 gene recorded a highly significant association p = 0.0009, and a high ratio in the control group (90%) in comparison with moderate cases of COVID-19 (60%). While the heterozygote genotype (GA) of the same gene showed a significant (p-value = 0.0144) and high ratio in moderate cases (30%) in comparison with the control group (10%). Conclusion(s): the wild genotype (GG) for Angiotensin convert-ing-enzyme 2 rs4646116 gene may be associated with more protection from infection with COVID-19. While the polymorphism heterozygote genotype (GA) for the same gene may be associated with more susceptibility to infection with COVID-19.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.
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Neuropilin-1 (NRP1) which is a main transmembrane cell surface receptor acts as a host cell mediator resulting in increasing the SARS-Cov-2 infectivity and also plays a role in neuronal development, angiogenesis and axonal outgrowth. The goal of this study is to estimate the impact of single nucleotide polymorphisms (SNPs) in the NRP1 gene on the function, structure and stabilization of protein as well as on the miRNA-mRNA binding regions using bioinformatical tools. It is also aimed to investigate the changes caused by SNPs in NRP1 on interactions with drug molecule and spike protein. The missense type of SNPs was analyzed using SIFT, PolyPhen-2, SNAP2, PROVEAN, Mutation Assessor, SNPs&GO, PhD-SNP, I-Mutant 3.0, MUpro, STRING, Project HOPE, ConSurf, and PolymiRTS. Docking analyses were conducted by AutoDock Vina program. As a result, a total of 733 missense SNPs were determined within the NRP1 gene and nine SNPs were specified as damaging to the protein. The modelling results showed that wild and mutant type amino acids had some different properties such as size, charge, and hydrophobicity. Additionally, their three-dimensional structures of protein were utilized for confirmation of these differences. After evaluating the results, nine polymorphisms rs141633354, rs142121081, rs145954532, rs200028992, rs200660300, rs369312020, rs370117610, rs370551432, rs370641686 were determined to be damaging on the structure and function of NRP1 protein and located in conserved regions. The results of molecular docking showed that the binding affinity values are nearly the same for wild-type and mutant structures support that the mutations carried out are not in the focus of the binding site, therefore the ligand does not affect the binding energy. It is expected that the results will be useful for future studies.
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Introduction The quest to understand the pathophysiology behind the deleterious effects of the coronavirus disease 2019 (COVID-19) outbreak took a turn when involvement of the angiotensin converting enzyme (ACE) receptors in different organs, especially the lungs, could explain all the clinical manifestations and adverse events in patients. The I/D polymorphism in the ACE gene, having been attributed in various studies, was also seen to have an effect in this pandemic. Present study aimed to analyze the effect of this I/D mutation in COVID-19 patients and in their healthy contacts. Methods Patients with past history of COVID-19 infection and their healthy contacts were enrolled in the study after obtaining ethical clearance and informed consent. The polymorphism was studied by real-time polymerase chain reaction (PCR). Data was analyzed in SPSS version 20 (IBM Corp., Armonk, NY, USA). p value less than 0.05 was taken as significant. Results The allelic distribution followed the Hardy-Weinberg equilibrium, with the wild 'D' allele being dominant in the population. Between the case and controls, the mutant 'I' allele was observed more in the controls, and the association was statistically significant. Conclusion From the results of the present study, it could be concluded that while the wild 'D' allele led to higher chances of being affected with COVID-19, the polymorphism to 'I' allele was relatively protective in nature.
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Background and Objectives: The COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus. Patients and methods: This study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction. Results: The frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p = 0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p < 0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p = 0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p = 0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants' genotypes (p = 0.016 and p = 0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer. Conclusion: In conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19.
Antecedentes y objetivos: La pandemia de COVID-19 surgió en China a fines de 2019 y se extendió rápidamente por todo el mundo. Existe evidencia de que la infección por COVID-19 puede verse influenciada por variaciones genéticas en el huésped. El objetivo de este estudio fue investigar la asociación entre el polimorfismo ACE InDel y COVID-19 en el norte de Chipre. Pacientes y métodos: Se incluyeron 250 pacientes diagnosticados de COVID-19 y 371 controles sanos. El genotipado del polimorfismo del gen ACE InDel se realizó mediante reacción en cadena de la polimerasa. Resultados: La frecuencia de homocigotos ACE DD aumentó significativamente en pacientes con COVID-19 en comparación con el grupo de control (p = 0,022). La diferencia en la presencia del alelo D entre los grupos de pacientes y control fue estadísticamente significativa (57,2% y 50,67%, respectivamente, p < 0,05). Las personas con el genotipo II tenían un mayor riesgo de COVID-19 sintomático (p = 0,011). Además, los hallazgos radiográficos de tórax se observaron con mayor frecuencia en individuos con el genotipo DD en comparación con los individuos con los genotipos ID y II (p = 0,005). Se encontró una diferencia estadísticamente significativa cuando se comparó el tiempo de aparición de los síntomas de COVID-19 y la duración del tratamiento con los genotipos de los participantes (p = 0,016 y p = 0,014, respectivamente). El tiempo de aparición de COVID-19 fue más corto en individuos con genotipo DD que en individuos con genotipo II, mientras que la duración del tratamiento fue más prolongada. Conclusiones: El polimorfismo ACE I/D podría predecir la gravedad de la COVID-19.
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Objectives: The objective of the current study was to check the link between potential polymorphism in IL12A rs568408 and the possible risk of COVID-19 in the Iraqi population. Materials and Methods: Allele specific-polymerase chain reaction (PCR) technique was carried out for genotyping and detection of IL12A rs568408 gene polymorphism in a case-control study of 125 severe COVID-19 cases and 60 controls. Patients were admitted to either Marjan medical city or Al-Sadeq hospital's COVID-19 wards between January and June 2022 in Iraq. The diagnosis of COVID-19 in each patient was confirmed by severe acute respiratory coronavirus 2-positive reverse transcription-PCR. Results: The distribution of both genotyping and allele frequencies of IL-12A rs568408 revealed significant differences between patients and control groups (P = 0.006 and P = 0.001, respectively). The IL12A rs568408 AA and AG variant genotypes were associated with a significantly increased risk of COVID-19 (odds ratio [OR] = 5.19, 95% confidence interval [CI]: 1.13-23.82; P = 0.034) and (OR = 2.39, 95% CI = 1.16-4.94, P = 0.018), respectively, compared with the wild-type GG homozygote. Conclusion: These findings indicate that IL12A rs568408 GA/AA variant may contribute to the risk of COVID-19. This study is the first report about the association of IL12A rs568408 with COVID-19.