GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19.
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ABSTRACT:
SUBMITTER: Coric V
PROVIDER: S-EPMC8721193 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a global pandemic on March 11, 2020. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has killed millions of people and had a terrible effect on society. The transmembrane protease serine 2 (TMPRSS2) enzyme is essential in the initial phases of the interplay between the SARSCoV-2 and the host cells by assisting viral entrance.MethodsThis observational case-control study involved 150 participants, 100 adult patients with COVID-19, 50 of whom appeared healthy and had no history of or symptoms of COVID-19 infection when the study was conducted. Between January and April 2022, patients were taken as inpatients in isolation units or through recruitment from the COVID-19 clinic at Kasr Al-Ainy Cairo University Hospitals. According to the National Institutes of Health guidelines (2021), they were categorised into three categories: mild, moderate, and severe. TMPRSS2 p.(Val197Met) variant genotyping was evaluated using TaqMan Real-Time PCR.ResultsThe study showed a substantial difference between the mild and severe COVID-19 patient groups regarding their TMPRSS2 (p.Val197Met) genotypes (P value = 0.046). The C allele was significantly more prevalent in the mild, moderate and severe COVID-19 patient categories (77.8%, 89.7% and 91.7%, respectively) and the control group (80%). Meanwhile, the T allele was more prevalent in the mild (22.2%) and control (20%) groups. There was a statistically significant difference in allelic distribution between the mild and severe groups (P value = 0.034).ConclusionThe study showed a connection between the TMPRSS2 gene variant p.(Val197Met) and the degree of illness. We concluded that the T(mutant) allele was protective against severe COVID-19 because it was linked to lesser disease severity.
| S-EPMC10802041 | biostudies-literature
Project description:The molecular processes and proteomic markers leading to tumor progression (TP) in cervical cancer (CC) are either unknown or only partially understood. TP affects metabolic and regulatory mechanisms that can be identified as proteomic changes. To identify which proteins are differentially expressed and to understand the mechanisms of cancer progression, we analyzed the dynamics of the tumor proteome in CC cell lines. This analysis revealed two proteins that are up-regulated during TP, GSTM3 and GSTP1. These proteins are involved in cell maintenance, cell survival and the cellular stress response via the NF-κB and MAP kinase pathways during TP. Furthermore, GSTM3 and GSTP1 knockdown showed that evasion of apoptosis was affected, and tumor proliferation was significantly reduced. Our data indicate the critical role of GST proteins in the regulation and progression of cervical cancer cells. Hence, we suggest GSTM3 and GSTP1 as novel biomarkers and potential therapeutic targets for treating cervical cancer.SignificanceCC is particularly hazardous in the advanced stages, and there are few therapeutic strategies specifically targeting these stages. We performed analyses on CC tumor proteome dynamics and identified GSTM3 and GSTP1 as novel potential therapeutic targets. Knockdown of these proteins showed that they are involved in cell survival, cell proliferation and cellular evasion of apoptosis.
| S-EPMC5955133 | biostudies-literature
Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
2022-03-01 | E-MTAB-10970 | biostudies-arrayexpress
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
| S-SCDT-EMM-2021-15227 | biostudies-other
Project description:We investigated the effect of IL-13 neutralization on COVID-19 disease progression in mice.
2021-07-23 | GSE180557 | GEO
Project description:In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity.
| S-EPMC7823574 | biostudies-literature
Project description:The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing.
| S-EPMC8512556 | biostudies-literature
Project description:IntroductionThe SARS-CoV-2 pandemic has been affecting the health and economic, as well as social, life of the entire globe since the end of 2019. The virus causes COVID-19, with a wide range of symptoms among the infected individuals, from asymptomatic infection to mortality. This, along with a high infection rate, prompted efforts to investigate the potential mechanisms of the different clinical manifestations caused by SARS-CoV-2 among the infected populations.HypothesisOne of the possible mechanisms that has been reported is the ABO blood system polymorphism. Indeed, one of the major proposed mechanisms is the presence of naturally occurring anti-A antibodies in individuals of groups O and B, which could be partially protective against SARS-CoV-2 virions.Objective and methodThis article aimed to review the published data on the potential effect of the ABO blood group system on the susceptibility to COVID-19 and the disease progression and outcomes.ResultsThe reviewed data suggest that individuals of blood group A are at a higher risk of infection with SARS-CoV-2 and may develop severe COVID-19 outcomes, whereas blood group O is considered protective against the infection, to some extent. However, some of the available studies seem to have been influenced by unaccounted confounders and biases.ConclusionTherefore, further appropriately controlled studies are warranted to fully investigate the possible association between the ABO blood groups and COVID-19 susceptibility and severity.
| S-EPMC8437766 | biostudies-literature
Project description:BackgroundAmple evidence indicates a sex-related difference in severity of COVID-19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity.ObjectiveTo test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients.Materials and methodsThis study included 1136 male patients infected with SARS-CoV-2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID-19 severity was assessed by Chi-squared (Chi2 ) and logistic regression analysis.ResultsThe mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis).DiscussionAndrogen sensitivity may be a critical factor in COVID-19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID-19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID-19 outcome.ConclusionsThe results obtained in our study do not support the role of this polymorphism as biomarker of COVID-19 severity.
| S-EPMC10098487 | biostudies-literature
Project description:Using RNA-seq and high-resolution mass spectrometry we performed a comprehensive systems analysis on 128 plasma and leukocyte samples from hospitalized patients with or without COVID-19 (n=102 and 26 respectively) and with differing degrees of disease severity. We generated abundance measurements for over 17,000 transcripts, proteins, metabolites, and lipids and compiled them with clinical data into a curated relational database. This resource offers the unique opportunity to perform systems analysis and cross-ome correlations to both molecules and patient outcomes. In total 219 molecular features were mapped with high significance to COVID-19 status and severity, including those involved in processes such as complement system activation, dysregulated lipid transport, and B cell activation. In one example, we detected a trio of covarying molecules – citrate, plasmenyl-phosphatidylcholines, and gelsolin (GSN) – that offer both pathophysiological insight and potential novel therapeutic targets. Further, our data revealed in some cases, and supported in others, that several biological processes were dysregulated in COVID-19 patients including vessel damage, platelet activation and degranulation, blood coagulation, and acute phase response. For example, we observed that the coagulation-related protein, cellular fibronectin (cFN), was highly increased within COVID-19 patients and provide new evidence that the upregulated proteoform stems from endothelial cells, consistent with endothelial injury as a major activator of the coagulation cascade. The abundance of prothrombin, which is cleaved to form thrombin during clotting, was significantly reduced and correlated with severity and might help to explain the hyper coagulative environment of SARS-CoV-2 infection. From transcriptomic analysis of leukocytes, we concluded that COVID-19 patients with acute respiratory distress syndrome (ARDS) demonstrated a phenotype that overlapped with, but was distinct from, that found in patients with non-COVID-19-ARDS. To aid in the global efforts toward elucidation of disease pathophysiology and therapeutic development, we created a web-based tool with interactive visualizations allowing for easy navigation of this systems-level compendium of biomolecule abundance in relation to COVID-19 status and severity. Finally, we leveraged these multi-omic data to predict COVID-19 patient outcomes with machine learning, which highlighted the predictive power of these expansive molecular measurements beyond the standardized clinical estimate of 10-year survival Charlson score.
2020-08-29 | GSE157103 | GEO