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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: 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 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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Background: The pathophysiology of viral-infections is highly complex and involves host immunocompetence, host genetics, and gene-environment interactions. We hypothesized that polymorphic variants in host genes, blood group and previous vaccination status against H1N1 may affect the clinical course of covid-19 infection. Method(s): A total of 202 subjects who were RT-PCR negative after Covid-19 infection were recruited. We investigated association between Covid-19 infection (Severity and recovery period) and multiple factors including ABO and Rh blood groups, H1N1 vaccination, polymorphism in Viral susceptibility genes (ACE2 G8790A), and polymorphism in host response genes (ACE I/D rs4646994, IL6- 174G/C, GSTT1/GSTM1 I/D and GSTP1 Ile 105 Val). Result(s): B-ve and O-ve ABO and Rh blood groups had significantly higher Covid-19 recovery period applied on one-vs.-all in a nonparametric t-test (p<0.05). Subjects who had vaccinated themselves against H1N1 presented with a lower recovery-period (p<0.05). Both variables (blood group and H1N1 vaccination) were not however associated with Covid-19 severity. Out of the studied polymorphisms, ACE2 G8790A and GSTT1/GSTM1 were significantly associated with covid-19 infection. Our results indicated that G/G genotype of ACE2 G8790A (OR 3.52, P 0.007) and GSTT1/ GSTM1 null (M1 - / - OR = 3.98, P = 0.0004;T1 - / - OR 3.84, P = 0.004) and double null (M1 - / - /T1 - / - OR = 9.66, P = 0.001) are likely to be associated with an increased risk for severe-critical outcomes in individuals with COVID-19. Other polymorphisms analyzed in this study were found to have no significant association with Covid-19 outcome. Conclusion(s): This study suggests that outcome of Covid-19 infection is affected by both clinical and genetic factors. Thus it seems plausible to utilize these factors as prediction and susceptibility markers in the prognosis of COVID-19, which may help to personalize the treatment.
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Objectives: Toll-like receptors (TLRs) are an important family of receptors that recognize infectious agents and play an important role in the innate immune system. TLRs are a potential candidate to control infection in the early stages of the disease and to produce vaccines against SARS-CoV-2. In addition, studies have suggested that TLR polymorphisms are also associated with antiviral responses against SARS-CoV-2. Therefore, we aimed to investigate the relationship of TLR7 and TLR8 polymorphisms with COVID-19 disease prognosis. Materials-Methods: A total of 120 COVID-19 patients, including 40 outpatients, 40 patients with mild and moderate clinical status, hospitalized and severe pneumonia, and 40 patients followed in the intensive care unit (ICU), were included in the study. The classification of disease severity was made according to WHO criteria. TLR7 (rs179009), TLR8 -129 C/G (rs3764879) and TLR8 Met1Val (rs3764880) polymorphisms were genotyped using the PCR-RFLP method. Result(s): Since TLR7 and TLR8 are located on the X chromosome, men and women were analyzed separately. There was no significant difference between the groups in terms of 3 polymorphisms in males. On the other hand, in women, individuals carrying AG genotype and G allele for TLR8 Met1Val polymorphism were found at a higher rate in patients hospitalized in ICU than in patients followed in the service (p <0.05). In terms of the other two polymorphisms, no significant difference was found between the groups in women. Conclusion(s): We suggest that the AG genotype and G allele of TLR8 Met1Val polymorphism can be considered as an important risk factor that increases the severity of the disease in women.
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Attention Deficit Hyperactivity Disorder (ADHD) is characterized by oppositional, defiant, disobedient, disruptive and also aggressive behavior. Many genes are involved in its onset, particularly dopaminergic pathway genes. Moreover, genetic predisposition to aggression appears affected by the polymorphic genetic variants of the serotoninergic system, among which, functional polymorphisms in monoamine oxidase A (MAOA). The risk of contracting coronavirus infection may arouse in some people severe emotional distress characterized by symptoms of fatigue, guilt, and aggression. A survey on the psychological impact of COVID-19 pandemic in Italian families of children with neurodevelopmental disorders such as ADHD showed how children have been particularly affected by the emergency. The aim of this study was to determine whether polymorphisms at the MAOA gene are associated with increased or reduced susceptibility to develop ADHD. Therefore, the variants rs6323, rs587777457 and rs1137070 of the MAOA gene were evaluated by SBT in 35 children (mean age 10.257 range 6-16) with ADHD and 27 healthy individuals. Our analysis allowed us to identify the G/G genotype of the variant rs6323 (Arg297Arg) was significantly associated with an increased risk of ADHD (p = 0.015). Allele G indicates higher levels of the enzyme, while the T allele indicates lower levels of enzyme production. When compared in patients, the G allele was associated with higher anger (p-value = 0.01) and might cause aggressive behavior in males. Our study shows that defining a genetic profile of ADHD can provide important information on the etiopathogenesis of the disease and help identify the best therapeutic option for patients with this disorder.
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Circadian rhythms, also known as circadian clocks, are cyclic endogenous biological patterns of an approximately 24-hour cycle which regulate the timing of physiology, metabolism, and behavior. Recent research in the field of circadian science has suggested that the timing of food intake may also play a role in markers of health, in addition to food choice and food quantity. There is emerging evidence suggesting that the timing of dietary intake, so-called chrono-nutrition, may be influenced by an individual<apos;>s chronotype. For example, the evening type has been linked to unhealthy diet, which could indicate a higher possibility of obesity. On the other hand, the continuum of chronotype diversity is largely mediated by genes. The presence of single nucleotide polymorphisms (SNP) of clock genes have been associated with obesity, chronotype, metabolic disturbances, and dietary habits (e.g., breakfast skipping, meal timing, energy/macronutrient intake). In this review, we outline the current knowledge of the interactions between clock genes, chronotype, dietary intake and chrono-nutrition.Additionally, it is emphasized that the COVID-19 pandemichas had a significant impact on the circadian system, dietary choices and meal timing. For this reason, the current review aims to focus on how chronotype/sleep and chrono-nutrition are affected during the COVID-19 pandemic.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.
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The clinical picture of COVID-19 ranges from asymptomatic to mild, moderate or severe disease sometimes leading to death. Differences in the interaction between SARS-CoV-2 Spike (S) protein and angiotensin converting enzyme 2 (ACE2) protein may lead to differences in disease severity. We studied whether ACE2 polymorphisms are associated with disease severity and outcome. We recruited 114 patients between July 2020 - March 2022 confirmed positive by RTPCR for COVID-19 with different degrees of severity (21 mild, 29 moderate, 34 severe, 30 death) and 30 controls (10 non-vaccinated+ 20 vaccinated) who were RT-PCR negative inspite of high-risk contact. Next-gen sequencing was done on MiSeq (Illumina) using amplicon-based targeted sequencing approach using a custom-designed panel to sequence all the exons of ACE2 gene. SPSS ver.26 was used for analysis. The following ACE2 variants were identified on the Local Run Manager (LRM) software from Illumina: (i) rs2285666 (c.439+4G>A) splice region variant, in controls (60%) and Patients (45.8%), (ii) rs4646140 (c.802+24G>A) intronic variant in 4/114 patients and 1/30 controls, (iii) rs41303171 ( c.2158A>G) missense variant in 2/114 patients, (iv) rs536749578 (c.2114+9T>C) intron variant, (v) rs763994205 (c.868A>C) missense variant and (vi) rs7595907 (c.656G>A) missense variant in 1/114 patient each only. rs2285666 was observed in equal frequency ( 60%) in vaccinated and non-vaccinated controls. rs2285666 was observed amongst different severity groups: Mild (80.95%), Moderate (37.93%), Severe (44.11%), and Death (56.67%) revealing association with disease severity, probably having a protective effect. However, these results need to be confirmed on larger sample sizes.
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A large number of studies show conflicting results and point to multiple factors that may influence the course of COVID-19 in patients with asthma: severity asthma, phenotypes, genetic characteristics, underlying asthma therapy, and comorbidities. The aim of the study was to determine the course of Covid-19 in patients with asthma depending on the Gln27Glu polymorphism of the ADRB2 gene in the Ukrainian population. Material(s) and Method(s): 553 patients with asthma were preliminarily examined and the distribution of ADRB2 genotypes was determined. Among these patients, 116 patients aged 18 to 70 suffered from mild, moderate and severe Covid-19. The diagnosis of asthma was established based on the GINA recommendations. The severity of Covid-19 is set according on the World Health Organization. Results of the study. Depending on the severity of Covid-19, patients with asthma were divided into 3 groups. Group I included 66 patients with a mild severity of Covid-19, group II - 33 patients with a moderate severity, and group III - 23 patients with a severe. After statistical processing of the data, the following frequencies of ADRB2 genotypes were obtained: in group I Gln27Gln-genotype - 93.9%, Gln27Glu-genotype - 6.1%, Glu27Glu-genotype - 0;in group II - 6.1%, 66.7%, 27.2%, respectively;and in group III - 5.9%, 11.8%, 82.3%, respectively. The obtained results indicate that the Gln27Gln- genotype was significantly more common in asthma patients with mild severity Covid-19, while the Glu27Glu-genotype was significantly more common in patients with severe Covid-19 (chi2 121.5;p < 0.001). Conclusion(s): A more severe course of Covid-19 in asthma patients is associated with the ADRB2 Glu27Glugenotype.
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BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHOD(S): We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40.0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1.0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi.Copyright © 2023 Elsevier Ltd. All rights reserved.
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Background: Diabetes mellitus (DM) represents one of the most common metabolic diseases in the world, with rising prevalence in recent decades. Most cases are generally classified into two major pathophysiological categories: type 1 diabetes mellitus (DM1), which progresses with absolute insulin deficiency and can be identified by genetic and pancreatic islet autoimmunity markers, and type 2 diabetes mellitus (DM2), which is the most prevalent form and involves a combination of resistance to the action of insulin with an insufficient compensatory response of insulin secretion. In the last two decades, in parallel with the increase in childhood obesity, there has also been an increase in the incidence of DM2 in young people in some populations. Other forms of diabetes may affect children and adolescents, such as monogenic diabetes (neonatal diabetes, MODY – maturity onset diabetes of the young, mitochondrial diabetes, and lipoatrophic diabetes), diabetes secondary to other pancreatic diseases, endocrinopathies, infections and cytotoxic drugs, and diabetes related to certain genetic syndromes, which may involve different treatments and prognoses. DM1 is considered an immuno-mediated disease that develops as a result of gradual destruction of insulin-producing pancreatic beta cells that eventually results in their total loss and complete dependence on exogenous insulin. Clinical presentation can occur at any age, but most patients will be diagnosed before the age of 30 years
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Background: to date, more than 243 million COVID-19 cases have been diagnosed globally, with 4.94 million deaths, 489.000 new cases and 8.474 deaths per day. In Italy there are currently 4.73 million cases and 132.000 deaths. It is well known that the entry of the SARS- CoV-2 virus into cells is mediated by the binding between the virus Spike-glycoprotein (S) and the membrane ACE2-receptor (ACE2-R). When SARS-CoV-2 binds to ACE2-R, with subsequent membrane fusion and virus entry into the cell, a down-regulation of these receptors occurs. ACE2 -R downregulation plays a crucial role in the pulmonary and systemic inflammatory response. A serious clinical course appears to be associated with some factors such as age, previous pathologies and comorbidities. However, also a dysregulation of the RAA system linked to a different expression of ACE-2 R and TMPRSS2 gene polymorphisms and different serum levels of soluble ACE2 (sACE2), could be associated with abnormal inflammatory and immune response to SARS-CoV-2 infection. Aim of the Study: we aimed to verify whether there is an association between the clinical course of COVID-19 patients (pts) and the presence of more frequent ACE2 and TMPRSS2 single-nucleotide polymorphisms (SNPs) and if sACE2 levels are related to specific ACE2 and TMPRSS2 polymorphic variants. Method(s): we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course;pts with symptomatic course but without the need for hospitalization for COVID-19;pts with severe symptomatic course requiring hospitalization in intensive care unit. Data about age, clinical course, comorbidities, and therapies were collected. Blood samples were taken for the genetic analysis of the most frequent SNPs of the ACE2-R and TMPRSS2 detected in Italian population, in particular genotypic variants TTand CC of ACE2 SNPs 1 and 5 (rate of 5% and 14% respectively) and genotypic variants TTand CC of TMPRSS2 SNPs 2 and 3 (rate of 50% and 30% respective). Result(s): among 178 pts enrolled up to March 2022, we have so far analyzed the genetic polymorphisms of 74 pts.;21 (28%) were hospitalized for COVID-19, 38 (51%) had symptomatic course without hospitalization and 15 (21%) were completely pauci-asymptomatics. Serum concentrations of sACE2 and distribution of polymorphic variants in the three groups are summarized in Table 1. We found that sACE2 levels were higher in genotypic variant CC of SNP 1 of TMPRSS2 gene (Table 2). Considering that a high concentration of sACE2 outlines a proinflammatory condition, it could be hypothesized that the CC genotype may be a predisposing condition to the cytokine storm of COVID-19. Perspective(s): Genetic analysis of ACE2 and TMPRSS2 SNPs will help to clarify the relationship between these polymorphic variant, sACE2 levels, risk of SARS-CoV2 infection and severity of clinical presentation of COVID-19 in patients with or without CV diseases.
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Objective The suppressor of cytokine signaling-1 (SOCS-1) gene is an essential physiological regulator of cytokine signaling. Tumor necrosis factor-alpha (TNF-alpha) is an important component of the immunological response. Herein, we aimed to investigate the effects of SOCS-1 (-1478 CA > Del) and TNF-alpha (-308) polymorphisms on disease susceptibility and prognosis in pediatric patients with coronavirus disease 2019 (COVID-19). Methods One-hundred fifty COVID-19 patients in the COVID-19 emergency department between September 2020 and April 2021 and 80 healthy volunteers (control group) without any additional disease were included. Baseline gene polymorphisms were compared between the patient and healthy control groups. Afterward, the gene polymorphism distribution was examined by forming two separate clinical patients' subgroups. Results While CA/CA and CA/Del gene variants of SOCS-1 were higher in the patient group, Del/Del genotype was more common in the control group (p < 0.05). The GG genotype of the TNF-alpha was significantly more common in the severe subgroup (p = 0.044). The GA genotype of TNF-alpha was associated with the risk of hospitalization (2.83-fold), while the GG genotype was found to be protective in terms of hospitalization (2.95-fold). Conclusions This study will be a guide in terms of the presence of high cytokine release genotypes and COVID-19-related cytokine release syndromes. Copyright © 2023 Georg Thieme Verlag. All rights reserved.
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Background: Cytokines are signaling molecules and involve lymphocytes and macrophages in the immune response. Lymphocyte-platelet adhesion is one of the mechanisms that ensure the cooperation of various subpopulations of cells and allow them to migrate through the vascular wall into the tissue. Aim(s): To study the function of lymphocyte-platelet adhesion depending on SNP of IL-2 (T330G) gene in healthy subjects and patients with COVID-19. Method(s): The research involved 168 patients with COVID-19 and 100 healthy people of the same age and gender. The participants of the study were Caucasian race and lived in the Trans-Baikal Territory. The examine of LPA was carried out by the method of Yuri Vitkovsky et al. (1999). The SNP of IL-2 (T330G) gene was determined by PCR. Such methods as Equilibrium Hardy-Weinberg, chi2-test, odds ratio descriptive statistics and the mean values (M) and standard deviation (SD) were used. Statistical significance was measured at the value p < 0.05. Result(s): We found all the studied IL-2 mutations in accordance with the Hardy-Weinberg law (p>0.05). The heterozygous T/G of IL-2 gene was registered significantly more frequently in the group of patients in comparison with the control group. Based on the obtained data on frequency distribution, the chance of developing SARS-COV- 2 increased in carriers of the allele T and the T/T genotype of IL-2 gene (p < 0.001). It was found that patients with SARS-COV- 2 had an increase in the LPA index compared to the group of healthy individuals (15.2 +/- 1.1%). The maximum amount of LPA was detected among patients with T/T genotype -39.7 +/- 2.1%, the minimum amount -in the owners of G/G (31.4 +/- 1.9%) (p< \0.001). Conclusion(s): 1) SARS-COV- 2 is accompanied by an increase in LPA function indicators, which depend on SNP of IL-2 (T330G) gene. 2) Carriers of allele T and T/T genotype of IL-2 gene (T330G) predispose to the development of COVID-19.
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Introduction and Aim: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. Once infected this virus induces several clinical disorders in humans. SARSCoV-2 enters cells via TMPRSS2. Genetic variation in TMPRSS2 could affect the severity of infection. The purpose of this study was to investigate how the (TMPRSS2) gene polymorphism affected COVID-19 severity in patients as well as the effect of age and comorbidities on infection. Material(s) and Method(s): This cross-sectional analytical study comprised of 400 (185 male, 215 female) Covid-19-infected patients between ages 18-65 receiving treatment in hospitals at Baghdad, Iraq. The patients were divided into three groups: mild, moderate, and severe based on the severity of Covid-19 infection. Baseline data was collected for each patient through interview and questionnaire. Blood collected from patients was subjected to DNA extraction and detecting polymorphisms within SNPs of the TMPRSS2 gene. Result(s): The present investigation indicated higher age to be significantly associated with severe COVID-19 infection when compared to moderate and mild infection (36.14 +/- 12.716 vs. 48.52 +/- 17.513 vs. 59.26 +/- 16.035) (F= 3.697, df: 64, P= 0.000). Patients with comorbidities was associated with a greater rate of severe Covid-19 infection (74.2% vs. 25.8%). However, individuals without comorbidities had a considerably lower rate of mild and moderate Covid-19 infection (13.9% vs. 86.1%) and (36% vs. 64%), respectively (x
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The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, Angiotensin Converting Enzyme 2 (ACE2). The depletion of the biological functions of ACE2, due to the internalization of the receptor along with SARS-CoV-2, leads to impairment of Renin Angiotensin System (RAS), which can contribute to COVID-19 pathogenesis. In addition, genetic differences in RAS may be associated with more severe symptoms and complications observed in COVID-19 patients. This study aims to perform a comparative analysis between COVID-19 positive patients and uninfected individuals, to correlate such disease profiles with ACE I/D (Insertion/Deletion) and ACE2 G8790A polymorphisms, and their enzymatic activities. The anthropometric, demographic, clinical and cardiovascular parameters of 764 individuals from Ipaussu/SP (Brazil) were evaluated. ACE and ACE2 activities were measured by fluorometric assays, and assessment of both enzymes polymorphisms was performed by PCR. In this cohort, 35,2% (269 of 764) the volunteers were positive for COVID-19. The prevalence of COVID-19 was higher among women (67%) and individuals aged between 18 and 49 years. Also, comorbidities as obesity and arterial hypertension were more frequent in the positive group, when considered individuals under 60 years old. Higher ACE and ACE2 enzymatic activities were observed in positive group (46.4 vs 41.6 and 11.3 vs 8.5, respectively). Individuals with ID genotype in the positive group presented higher ACE activity compared to individuals with same genotype in control group (46.9 vs 41.7). In the positive group, ACE activity was increased in the DD (54.5) when compared to ID (46.9) and II (37.9) genotypes. No significant differences related to ACE2 activity and polymorphism were observed. ACE/ACE2 activity ratio was higher in the COVID-19 negative group (4.7 vs 3.7). The increased ACE activity for the DD genotype was in line with the literature data for hypertension and cardiovascular diseases. We can suggest a synergic effect between ACE DD genotype and COVID-19 infection enhancing ACE activity, what may contribute to pro-inflammatory phenotype and more severe symptoms of COVID-19.
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The clinical spectrum of COVID-19 is extremely variable. Thus, it is likely that the heterogeneity in the genetic make-up of the host may contribute to disease severity. Toll-like receptor (TLR)8 plays a vital role in the innate immune response to SARS-CoV-2 infection. We genotyped 60 adult COVID-19 samples taken from 20 patients, 20 recovery persons and 20 healthy people for TLR8 (rs3764880 A/G) polymorphisms usingTetra-ARMS Technique. The frequency of alleles of TLR8 gene polymorphism of A allele is 57.5% in patients and 60.0% in control group, while frequency of G allele is 42.5% in patients and 40.0% in control group. While, the frequency of alleles of TLR8 gene polymorphism of A allele is 55.0% in recovery and 60.0% in control group, while frequency of G allele is 45.0% in recovery and 40.0% in control group.
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Introduction: Adolescents' cognitive performance is impacted by factors such as sleep habits, chronotypes and also genetic characteristics. The periods of human sleep and wakefulness are controlled by homeostatic and circadian factors, which the combination generates variations in the preferences for hours of activity and rest, called chronotypes. Chronotypic classification impacts cognitive skills such as logic and problem solving. In adolescence, there is a greater tendency to evening chronotype. The neural factor called BDNF, Brain- Derived Neurotrophic Factor, showed a significant role in cognitive performance variations as in different sleep patterns. The human BDNF gene has a frequent polymorphism called Val66Met, related to several cognitive functions and different patterns of sleep and circadian rhythm. Objective: Evaluate the association of BDNF Val66Met polymorphism with circadian patterns and cognitive performance on tests of attention, in high school students. Methods: High school students, aged between 15 and 17 years old were included in the study, whose cognitive attention skills were investigated by the Psychological Battery for Assessment of Attention. Their BDNF genotypes were determined by analyzing self-collected oral cell samples, which were amplified by real-time PCR using fluorescent probes. Chronotypic characteristics were evaluated by completing two morningness and eveningness scales. Because of the pandemic of COVID-19, a questionnaire about the presence of symptoms, in the previous days of the tests, was included. At present, volunteers are being evaluated through actigraphy. Results: Eighty-five adolescents were evaluated in that study. The average attention score of students who study in the afternoon was lower than individuals who study in the morning. The average score attention for the female gender was significantly lower than that obtained for the male gender. The students who reported symptoms of COVID- 19 had a significantly lower attention score. Lastly, there was no correlation between the chronotype defined by the scales, the performance in the attention test, or even the BDNF genotype of the participants. Conclusion: The central findings obtained, in the first phase of the study, complement the understanding of the associations between the parameters of cognition, chronobiology and genetic aspects. In the next phase, the use of actigraphy will make it possible to deepen these analyzes and conclusions.
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Objectives: The development of effective targeted therapy and drug-design approaches against the SARS-CoV-2 is a universal health priority. Therefore, it is important to assess possible therapeutic strategies against SARS-CoV-2 via its most interaction targets. The present study aimed to perform a systematic review on clinical and experimental investigations regarding SARS-COV-2 interaction targets for human cell entry. Methods: A systematic search using relevant MeSH terms and keywords was performed in PubMed, Scopus, Embase, and Web of Science (ISI) databases up to July 2021. Two reviewers independently assessed the eligibility of the studies, extracted the data, and evaluated the methodological quality of the included studies. Additionally, a narrative synthesis was done as a qualitative method for data gathering and synthesis of each outcome measure. Results: A total of 5610 studies were identified, and 128 articles were included in the systematic review. Based on the results, spike antigen was the only interaction protein from SARS-CoV-2. However, the interaction proteins from humans varied including different spike receptors and several cleavage enzymes. The most common interactions of the spike protein of SARS-CoV-2 for cell entry were ACE2 (entry receptor) and TMPRSS2 (for spike priming). A lot of published studies have mainly focused on the ACE2 receptor followed by the TMPRSS family and furin. Based on the results, ACE2 polymorphisms as well as spike RBD mutations affected the SARS-CoV-2 binding affinity. Conclusion: The included studies shed more light on SARS-CoV-2 cellular entry mechanisms and detailed interactions, which could enhance the understanding of SARS-CoV-2 pathogenesis and the development of new and comprehensive therapeutic approaches.