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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: Genetic variants affecting host defense against pathogens may help explain COVID-19 fatal outcomes. Our aim was to identify rare genetic variants related to COVID-19 severity in a selected group of patients under 60 years who required intubation or resulting in death. Method(s): Forty-four very severe COVID-19 patients were selected from the Spanish STOP-Coronavirus cohort, which comprises more than 3,500 COVID-19 patients. Genotype was performed by whole exome sequencing and variants were selected by using a gene panel of 867 candidate genes (immune response, primary immunodeficiencies or coagulation, among other). Variants were filtered, priorized and their potential pathogenicity was assessed following ACGM criteria. Result(s): We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic (26%). Mostly, the candidate variants were located in genes related to immune response (38%), congenital disorders of glycosylation (14%) or damaged DNA binding genes (9%). A network analysis, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks enriched in carbohydrate metabolism and in DNA metabolism and repair processes. Conclusion(s): The variants identified affect different, but interrelated, functional pathways such as immune response and glycosylation. Further studies are needed for confirming the ultimate role of the new candidate genes described in the present study on COVID-19 severity.
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Host genetic susceptibility is a key risk factor for severe illness associated with COVID-19. Despite numerous studies of COVID-19 host genetics, our knowledge of COVID-19-associated variants is still limited, and there is no resource comprising all the published variants and categorizing them based on their confidence level. Also, there are currently no computational tools available to predict novel COVID-19 severity variants. Therefore, we collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. We further evaluated the classifier's predictions using feature importance analyses to investigate the biological properties of COVID-19 susceptibility variants, which identified conservation scores as the most impactful predictive features. The results of enrichment analyses revealed that genes carrying high-confidence COVID-19 susceptibility variants shared pathways, networks, diseases and biological functions, with the immune system and infectious disease being the most significant categories. Additionally, we investigated the pleiotropic effects of COVID-19-associated variants using phenome-wide association studies (PheWAS) in ~40,000 BioMe BioBank genotyped individuals, revealing pre-existing conditions that could serve to increase the risk of severe COVID-19 such as chronic liver disease and thromboembolism. Lastly, we generated a web-based interface for exploring, downloading and submitting genetic variants associated with COVID-19 susceptibility for use in both research and clinical settings (https://itanlab.shinyapps.io/COVID19webpage/). Taken together, our work provides the most comprehensive COVID-19 host genetics knowledgebase to date for the known and predicted genetic determinants of severe COVID-19, a resource that should further contribute to our understanding of the biology underlying COVID-19 susceptibility and facilitate the identification of individuals at high risk for severe COVID-19.Copyright © 2023 Elsevier Inc.
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Morocco is one of the most important fig (Ficus carica L.) diversity hotspots globally, where its cultivation is ancestral. This large diversity, alongside its valorization, has gone unheeded for many reasons, some of which have to do with ancient agricultural strategies besides the lack of exhaustive studies. Although being the third worldwide fig producer, Moroccan fig remains less competitive in the international market because of the poorly structured value chain and the lack of efficient marketing strategies. The current chapter aims to assess the fig genetic and chemotypic diversity hosted in Moroccan agroecosystems and the nutritional values of this typical seasonal fruit alongside its positive effects on human health. A particular interest is also given to examining the potential and emerging valorization pathways of fig and its bioproducts. This chapter also provides a critical analysis of fig value chain and market structure, focusing on the sector resilience towards various chocks. The latter, including the recent socioeconomic crisis provoked by COVID-19, is a challenging endeavor since the sector is poorly organized, making it more vulnerable to global changes. This may impact the local population, mainly where this crop constitutes the main income source. Through this chapter, a holistic view of fig diversity and valorization patterns, along with its value chain resilience to a wide range of factors and conditions, explores solutions to the benefit of policy makers, industry, and end-users. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023. All rights reserved.
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Background/Objectives: COVID-19 can affect anyone with the disease's symptoms ranging from mild to very severe. Although environmental, clinical, and social factors play an important role in the disease process, host genetic factors are not negligible either. In the present article, we attempted to elaborate on the spectrum of risk variants and genes identified in different ways and their possible relationship to COVID-19 severity and/or mortality. Method(s): We present three different approaches to search host genetic risk factors that influence the development of COVID-19 disease. First, we analyzed the exome sequencing data obtained from Slovak patients who died of COVID-19. Second, we selected risk factors/genes that were associated with COVID-19. Finally, we compared each group of found risk variants with data from dead patients and two control groups, worldwide public data of the Non-Finnish European population from the gnomAD database, and genetic data from Non-invasive prenatal testing in the Slovak population. Result(s): We illustrate the utility of genomic data showed strong association in meta-analyses conducted by the COVID-19 HGI Browser. Conclusion(s): To our knowledge, the present study is the first population analysis of COVID-19 variants worldwide and also in the Slovak population that provides different approaches to the analysis of genetic variants in whole-exome sequencing data from patients who have died of COVID-19.
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Background/Objectives: Emerging evidence suggests that complement system infection-dependent hyperactivation may worsen COVID-19 outcome. We investigated the role of predicted high impact variants -referred as Qualifying Variants (QVs) -of complement system genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. Method(s): Exploiting Whole-Exome Sequencing (WES) data and 56 complement system genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (age >= 60 y.o.) and 56,885 European individuals from the gnomAD database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized COVID-19 patients. Result(s): We found an enrichment of QVs in three genes (MASP1, COLEC10 and COLEC11), which belong to the lectin pathway, in the asymptomatic cohort. Moreover, individuals with QVs showed lower serum levels of Masp1 and of prothrombin activity compared to controls while no differences were observed for CH50 and AH50 levels that measure the activity of classical and alternative complement pathways, respectively. Finally, integrative analyses of genome-wide association study and expression quantitative loci traits data showed a correlation between polymorphisms associated with asymptomatic COVID-19 and decreased expression of MASP1, COLEC11 and COLEC10 genes in lung tissue. Conclusion(s): This study suggests that rare genetic variants can protect from severe COVID-19 by mitigating the activation of lectin pathway and prothrombin activity.
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Listeriosis is a saprozoonotic infection that occurs when eating foods contaminated with Listeria. Invasive forms of listeriosis can have extremely severe consequences. Respiratory viral diseases predispose to the occurrence of combined viral-bacterial infections. With a mixed infection of listeriosis and COVID-19, a severe course of the disease is observed, which has a serious prognosis. The aim of the study was to analyze the frequency of various variants of invasive listeriosis and their outcomes in the period before the COVID-19 pandemic and against the background of its development, as well as to determine the genetic diversity of L. monocytogenes isolates. Material and methods. We analyzed 55 cases of invasive listeriosis in patients observed in 2018-2021 in various medical organizations in Moscow. The diagnosis was established on the basis of epidemiological, clinical and laboratory data, listeriosis was confirmed by bacteriological and molecular genetic methods, COVID-19 was confirmed by the detection of SARS-CoV-2 RNA in an oropharyngeal swab using real-time RT-PCR, as well as computed tomography of the lungs. Results. During the current COVID-19 pandemic (2020-2021), the incidence of listeriosis in pregnant women and invasive listeriosis occurring in the form of sepsis and/or lesions of the central nervous system did not differ significantly from similar indicators registered in 2018-2019. Listeria sepsis and/or meningitis/meningoencephalitis in association with severe SARS-CoV-2 novel coronavirus infection are at high risk of death. During the years of the COVID-19 pandemic, the diversity and range of L. monocytogenes genotypes in invasive listeriosis changed, new genotypes appeared that were not previously characteristic of the Russian Federation. Conclusion. The likelihood of developing listeriosis sepsis and/or meningitis/meningoencephalitis against the background of a severe course of COVID-19, and a high risk of an adverse outcome, require increased awareness of medical workers in the field of diagnosis and treatment of invasive listeriosis in order to conduct the earliest and most adequate antibiotic therapy.Copyright © 2022 Geotar Media Publishing Group. All Rights Reserved.
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The incidence of new coronavirus infection (COVID-19) varies significantly between countries and continents. Until now, there has been no clear explanation for this observation. Epidemiological studies have demonstrated a large difference in infection and mortality rates between men and women. This may be due to the gender difference in the polymorphism of genes linked to the X chromosome, which play an important role in the immune response. In addition, there is a different degree of severity of the disease: from an asymptomatic course and mild symptoms to a life-threatening condition requiring hospitalization in the intensive care unit and artificial lung ventilation. Several factors are associated with the severity of COVID-19, such as elderly age, multiple comorbid diseases, smoking, hypercholesterolemia, etc. However, we observe that severe disease is also observed in patients who do not have the above risk factors. In recent months, severe forms of COVID-19 have been reported in children, including early infancy. In this connection, it is relevant, in our opinion, to focus the problem on genetic factors, such as the carriage of single-nucleotide polymorphisms, which can affect susceptibility to infection and variability in the severity of the disease.Copyright © 2022 Sorbtsionnye i Khromatograficheskie Protsessy. All rights reserved.
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Introduction. The rapid spread of a new coronavirus infection among populations in many countries worldwide has contributed to the genetic evolution of the virus, resulting in the emergence of multiple genetic variants of the SARSCoV-2 coronavirus. Mutations in the viral genome can affect the ability of the virus to bypass the immune system and complicate development of diagnostic and prophylactic drugs. Data on the neutralizing activity of the sera obtained against previously circulating genetic variants of the virus in relation to current SARS-CoV-2 strains may serve as a scientific basis for the selection of the antigens in vaccine development. The aim of this work was to study cross-reactivity of SARSCoV-2 coronavirus strains belonging to different genetic variants, which were isolated in the territory of the Russian Federation during 2020-2022 in the neutralization reaction using mouse hyperimmune sera. Materials and methods. Ten strains of SARS-CoV-2 coronavirus belonging to different genetic variants were used (three non-VOC strains, alpha, beta, gamma, delta, delta+AY, omicron 1 and omicron 2). The hCoV-19/Australia/VIC01/2020 strain (Wuhan) was included in the study as a prototypical variant. BALBc mice were immunized with inactivated concentrated antigen mixed with a 1:1 adjuvant, which was a virus-like immunostimulatory complex based on Quillaja saponaria (Quillaja saponaria). The antibody titer was determined in the neutralization reaction. Results. Essential decrease of neutralizing ability of antibodies specific to non-vOC genetic variants of SARS-CoV-2 coronavirus was revealed against beta VOC and to a lesser degree against alpha and gamma VOC variants. The differences in the neutralizing activity level of antibodies for alpha and beta VOC variants are not significant among themselves, and with gamma VOC variants - there are no significant differences. Neutralizing ability of antibodies specific to delta VOC against alpha and beta VOC variants decreased 4-fold. Neutralizing activity of sera obtained to omicron 1 and 2 variants in relation to the prototype coronavirus variant was reduced 18-fold, to the gamma variant - 12-fold, to delta variants - more than 30-fold;for other variants it was even lower. Conclusions. The results obtained testify to the presence of cross-reactivity between strains of coronavirus belonging to genetic lines Wuhan, alpha, beta, gamma;it is weaker for delta variants. Mutations in the genome of VOC omicron variants led to a significant decrease in antigenic cross-links with earlier genetic variants of the coronavirus. These findings explain the low efficacy of vaccines based on the Wuhan strain, synthetic immunogens, and recombinant proteins based on it against omicron VOC variants, which have caused a rise in morbidity since early 2022, as well as cases of re-infection of humans with new genetic variants of the coronavirus.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.
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Background: The COVID-19 pandemic has been striking for three years and, despite the regular arise of new variants, populations are now widely immune and protected from severe symptoms. However, immunocompromised patients still have worse clinical outcomes, higher mortality and rarely develop effective immunity through vaccination or infection. Here, we studied the temporal distribution of infections, viral loads (VL) as well as the viral genetic diversity among an immunocompromised patient cohort, between January 2021 and September 2022. Method(s): Overall, 478 immunocompromised patients (solid organ transplant, HIV positive, cancer, autoimmune disease) and 234 controls (healthcare workers) from Pitie-Salpetriere and Bichat Claude-Bernard University hospitals (Paris, FRANCE) were diagnosed with SARS-CoV-2 infection by RT-qPCR. Whole genome sequencing was performed according to ARTIC protocol on Oxford Nanopore platform. All 712 full viral genomes were used to determine lineages and mapped to Wuhan-Hu-1 reference to produce a maximum likelihood phylogenetic tree (IQTree, 1000 bootstraps). Differences in temporal distributions of infections and VL were assessed using nonparametric statistical tests. Result(s): According to phylogenetic analysis, genomes from SARS-CoV- 2 infecting immunocompromised patients and those infecting healthy individuals are distributed in a similar way. No significant genetic differences can be observed between viral genomes from patients and controls within the different lineages. Temporal distribution of COVID-19 infections were also similar between immunocompromised patients and controls, with the exception of BA.2 variant for which controls were infected earlier (p< 0.001). VL were significantly lower in immunocompromised patients infected with Omicron variants (p=0.04). No differences in VL were observed for Alpha and Delta variants. Conclusion(s): At diagnosis, no intrinsic genetic divergence was observed in virus infecting immunocompromised patients compared to those circulating in the general population. Similarities in temporal distribution of infections between controls and patients suggest that these different groups become infected concomitantly. VL appeared to be lower for Omicron variants in immunocompromised patients. An earlier VL peak of Omicron and a testing of immunocompromised patients hospitalized once severe symptoms have appeared could indicate a delayed testing in these patients, once the replicative phase over. (Figure Presented).
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Since the outbreak of COVID-19, severe acute respiratory syndrome coronavirus 2 genome is still mutating, forming a variety of variants with strong transmission capacity, causing the spread of the epidemic worldwide, posing a serious threat to people's physical and mental health, and posing a major challenge to global public health. Omicron remains the main variant in several outbreaks worldwide, accounting for about 99% of the global genetic sequence. Recently, the World Health Organization announced that the subvariant of Omicron BA.5 has been found in more than 100 countries and regions around the world, causing the global epidemic rebound. However, there are few studies on the subvariant BA.5. This article reviews the latest research progress in epidemiology, infectivity, pathogenicity, vaccine and monoclonal antibody protection against Omicron subvariant BA.5, in order to provide reference for scientific prevention and control of Omicron subvariant BA.5.
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Infectious diseases, due to their epidemic potential, are capable of global spread, they are unpredictable, and their effective control is possible only on a planetary scale. In no other field of medicine, such radical and often unpredictable changes occur in a short time in the form of the elimination of individual diseases, the identification of a large number of previously unknown and the return of already forgotten diseases, a significant change in the pathogenesis and clinical symptoms of a significant number of them. Under these conditions, these changes often create problems for the health authorities and the public, ahead of their ability to recognize and respond in a timely manner to the emergence of epidemics and the transformation of pathological manifestations. Significant recent scientific progress has only slightly clarified our knowledge of the biological and genetic diversity of pathogens. Until now, the entire spectrum of infectious pathology remains unclear, and its numerous manifestations often take even experienced specialists by surprise. Evidence of our limited knowledge and ability to control the situation is the ongoing COVID-19 pandemic for three years now, the increasingly frequent detection of "new" infections, the return of infections declared defeated, evidence of the role of infectious factors in the etiology of many other human diseases.Copyright © 2023 Izdatel'stvo Meditsina. All rights reserved.
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Objective: Epidemiology and genetic variations of the infectious bronchitis virus(IBV) in Fujian province were studied. Method: Two strains of virus isolated from the diseased chickens in Fujian in 2021 were identified by chicken embryo pathogenicity test, electron microscope observation, and RT-PCR. S1 genes of the isolates were cloned, sequenced, and analyzed using biological software. Result: The two IBV strains were code named FJ-NP01 and FJ-FZ01. The full length of S1 of FJ-NP01 was 1 629 nt encoding 543 amino acids, and that of FJ-FZ01, 1 620 nt encoding 540 amino acids. The S1 gene cleavage site of FJ-FZ01 was HRRRR, same as all reference strains of genotype I branch;while that of FJ-NP01 HRRKR differed from the reported site of IBV isolated from genotype IV but same as that of TC07-2 reference strain of genotype VI. The homology of nucleotide and amino acid between the two isolates was 83.2% and 79.6%, respectively, but merely 75.7%-76.3%and 77.1%-83.5% with the Mass-type conventional vaccines H120 and H52, respectively. Further analysis showed that FJ-NP01was from a recombination event between CK CH GD LZ12-4 and L-1148, the homology of nucleotide acid between 1438-1506 nt of FJ-NP01 with CK CH GD LZ12-4 was 97%, and 95.9% between the other nucleotide acid of S1 gene with L-1148. Conclusion: It appeared that the IBV epidemic experienced in the province was complex in nature and that the existing Mass vaccines would not provide sufficient immune protection to deter the spread.
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Background: Immunocompromised hosts with prolonged SARS-CoV-2 infections have been associated with the emergence of novel mutations, especially in the Spike protein, a key target for vaccines and therapeutics. Here, we conducted a case-control study to measure the genetic diversity of SARSCoV- 2 and to search for immunocompromised-specific minority variants. Method(s): SARS-CoV-2-positive patients with lung/cardiac/kidney transplant, HIV-positive, or treated with high doses of corticosteroids for auto-immune diseases were considered as immunocompromised hosts. SARS-CoV-2-positive healthcare workers with no auto-immune disease were used as controls. Samples were analyzed by RT-qPCR at Pitie-Salpetriere and Bichat Claude-Bernard university hospitals (Paris, France). Samples with Cycle threshold < 30 were selected for SARSCoV- 2 whole-genome sequencing using Oxford Nanopore protocol. Raw sequence data were mapped onto the Wuhan-Hu-1 reference genome, and consensus sequences were produced to determine the lineage. Only sequences covering at least 95% at >=50X depth of the Spike gene were investigated. In-house algorithms were developed to identify all majority and minority mutations in Spike. We defined a minority variant when it was present in >=6% and < 50% of the reads;and a majority variant when it was present in >50%. Result(s): We sequenced SARS-CoV-2 genome from 478 COVID-19- positive immunocompromised patients and 234 controls. More minority non-synonymous mutations in Spike were detected in viruses from immunocompromised hosts, compared to viral genomes from controls, in both Delta (p=0.001) and Omicron (p< 0.001) lineages, but not in Alpha (p=0.66) (Figure 1). Interestingly, among the 52 patients infected with the Delta variant, we concomitantly detected at low frequencies the mutations H655Y, N764K, D796Y, in three patients (associated with different auto-immune disease), that are part of Omicron variants signature mutations. Similarly, some patients (n=7) infected by Omicron BA.1 lineage had R346T at low-frequency, later fixed in Omicron BA.4.6 and BQ.1.1 lineages. None of these mutations were observed in the viral genomes from controls. Conclusion(s): Here, we report a higher genetic diversity in Spike gene among SARS-CoV-2 sequences from immunocompromised hosts for Delta and Omicron lineages. These results suggest that immunocompromised patients are more likely to allow viral genetic diversification and are associated with a risk of emergence of novel SARS-CoV-2 variants. (Figure Presented).
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Quinoa (Chenopodium quinoa) is a grain-like, genetically diverse, highly complex, nutritious, and stress-tolerant food that has been used in Andean Indigenous cultures for thousands of years. Over the past several decades, numerous nutraceutical and food companies are using quinoa because of its perceived health benefits. Seeds of quinoa have a superb balance of proteins, lipids, carbohydrates, saponins, vitamins, phenolics, minerals, phytoecdysteroids, glycine betaine, and betalains. Quinoa due to its high nutritional protein contents, minerals, secondary metabolites and lack of gluten, is used as the main food source worldwide. In upcoming years, the frequency of extreme events and climatic variations is projected to increase which will have an impact on reliable and safe production of food. Quinoa due to its high nutritional quality and adaptability has been suggested as a good candidate to offer increased food security in a world with increased climatic variations. Quinoa possesses an exceptional ability to grow and adapt in varied and contrasting environments, including drought, saline soil, cold, heat UV-B radiation, and heavy metals. Adaptations in salinity and drought are the most commonly studied stresses in quinoa and their genetic diversity associated with two stresses has been extensively elucidated. Because of the traditional wide-ranging cultivation area of quinoa, different quinoa cultivars are available that are specifically adapted for specific stress and with broad genetic variability. This review will give a brief overview of the various physiological, morphological and metabolic adaptations in response to several abiotic stresses.
Subject(s)
Chenopodium quinoa , Adaptation, Psychological , Vitamins , Acclimatization , BetaineABSTRACT
Susceptibility to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the disease COVID-19, may be understood more clearly by looking at genetic variants and their associations to susceptibility phenotype. I conducted a genome-wide association study of SARS-CoV-2 susceptibility in a multiethnic set of three populations (European, African, and South Asian) from a UK BioBank clinical and genomic dataset. I estimated associations between susceptibility phenotype and genotyped or imputed SNPs, adjusting for age at enrollment, sex, and the ten top principal components of ancestry. Three genome-wide significant loci and their top associated SNPs were discovered in the European ancestry population: SLC6A20 in the chr3p21.31 locus (rs73062389-A;P=2.315 x 10-12), ABO on chromosome 9 (rs9411378-A;P=2.436 x 10-11) and LZTFL1 on chromosome 3 (rs73062394;P=4.4 x 10-11);these SNPs were not found to be significant in the African and South Asian populations. A multiethnic GWAS may help elucidate further insights into SARS-CoV-2 susceptibility.
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During the first and second waves of coronavirus-19 disease, Sardinia had one of the lowest hospitalization and related mortality rates in Europe. However, in contrast with this evidence, the Sardinia population showed a very high frequency of the Neanderthal risk locus variant rs35044562, considered to be a major risk factor for a severe SARS-CoV-2 disease course. We evaluated 358 patients who had tested positive for SARS-CoV-2 and 314 healthy Sardinian controls (Italy). Patients were divided according to WHO classification: 120 patients asymptomatic, 90 pauci-symptomatic, 108 with a moderate disease course and 40 severely ill. The allele frequencies of Neanderthal-derived genetic variants reported as being protective (rs1156361) or causative (rs35044562) for severe illness were calculated in patients and controls. The Thalassemia variant (rs11549407), the HLA haplotypes, the KIR genes, as well as KIRs and their HLA class I ligand combinations were also investigated. The rs35044562 and rs1156361 Neanderthal variants revealed a distribution in Hardy-Weinberg equilibrium (HWE) both in SARS-CoV-2 patients and the control population (X2HWE = 0.82, p = 0.37 and X2HWE = 0.13, p = 0.72, respectively). Our findings reported an increased risk for severe disease in Sardinian patients carrying the rs35044562 high-risk variant [OR 5.32 (95% CI 2.53-12.01), p<0.0001]. Conversely, the protective effect of the HLA-A*02:01~B*18:01~DRB1*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 - 41.0), p<0.0001]. This result suggests that the balance between risk and protective immunogenetic factors plays an important role in the evolution of COVID-19. A better understanding of these mechanisms may well turn out to be the biggest advantage in the race for the development of more efficient drugs and vaccines.
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Infectious diseases, due to their epidemic potential, are capable of global spread, they are unpredictable, and their effective control is possible only on a planetary scale. In no other field of medicine, such radical and often unpredictable changes occur in a short time in the form of the elimination of individual diseases, the identification of a large number of previously unknown and the return of already forgotten diseases, a significant change in the pathogenesis and clinical symptoms of a significant number of them. Under these conditions, these changes often create problems for the health authorities and the public, ahead of their ability to recognize and respond in a timely manner to the emergence of epidemics and the transformation of pathological manifestations. Significant recent scientific progress has only slightly clarified our knowledge of the biological and genetic diversity of pathogens. Until now, the entire spectrum of infectious pathology remains unclear, and its numerous manifestations often take even experienced specialists by surprise. Evidence of our limited knowledge and ability to control the situation is the ongoing COVID-19 pandemic for three years now, the increasingly frequent detection of "new" infections, the return of infections declared defeated, evidence of the role of infectious factors in the etiology of many other human diseases.Copyright © 2023 Izdatel'stvo Meditsina. All rights reserved.
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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.