Hypotheses and facts for genetic factors related to severe COVID-19.
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ABSTRACT:
SUBMITTER: Kotsev SV
PROVIDER: S-EPMC8316875 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-BSST416 | biostudies-other
Project description:BackgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was varied in disease symptoms. We aim to explore the effect of host genetic factors and comorbidities on severe COVID-19 risk.MethodsA total of 20,320 COVID-19 patients in the UK Biobank cohort were included. Genome-wide association analysis (GWAS) was used to identify host genetic factors in the progression of COVID-19 and a polygenic risk score (PRS) consisted of 86 SNPs was constructed to summarize genetic susceptibility. Colocalization analysis and Logistic regression model were used to assess the association of host genetic factors and comorbidities with COVID-19 severity. All cases were randomly split into training and validation set (1:1). Four algorithms were used to develop predictive models and predict COVID-19 severity. Demographic characteristics, comorbidities and PRS were included in the model to predict the risk of severe COVID-19. The area under the receiver operating characteristic curve (AUROC) was applied to assess the models' performance.ResultsWe detected an association with rs73064425 at locus 3p21.31 reached the genome-wide level in GWAS (odds ratio: 1.55, 95% confidence interval: 1.36-1.78). Colocalization analysis found that two genes (SLC6A20 and LZTFL1) may affect the progression of COVID-19. In the predictive model, logistic regression models were selected due to simplicity and high performance. Predictive model consisting of demographic characteristics, comorbidities and genetic factors could precisely predict the patient's progression (AUROC = 82.1%, 95% CI 80.6-83.7%). Nearly 20% of severe COVID-19 events could be attributed to genetic risk.ConclusionIn this study, we identified two 3p21.31 genes as genetic susceptibility loci in patients with severe COVID-19. The predictive model includes demographic characteristics, comorbidities and genetic factors is useful to identify individuals who are predisposed to develop subsequent critical conditions among COVID-19 patients.
| S-EPMC10169198 | biostudies-literature
Project description:Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk-factor for severe disease. Inflammation is central to the aetiology of both conditions where immune responses influence disease course. Identifying at-risk groups through immuno-inflammatory signatures can direct personalised care and help develop potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leukocyte populations in circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia, of CD8+ lymphocytes, was associated with severe COVID-19 and intensive care admission in non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia of classical monocytes were specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Over-expression of inflammatory markers reminiscent of the type-1 interferon pathway underlaid the immunophenotype associated with T2D. These changes may contribute to severity of COVID-19 in T2D. These findings show characteristics of severe COVID-19 in T2D as well as provide evidence that type-1 interferons may be actionable targets for future studies.
| S-SCDT-EMM-2020-13038 | biostudies-other
Project description:The study aims at investigating the specifical transcriptional signatures of severe COVID-19
2021-01-15 | GSE164805 | GEO
Project description:Analysis of COVID-19 hospitalized patients, with different kind of symptoms, by human rectal swabs collection and 16S sequencing approach.
2022-09-22 | E-MTAB-12236 | biostudies-arrayexpress
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress
Project description:Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19-associated respiratory failure. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-associated pneumonia in the native lung. Most importantly, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report results of the first successful lung transplantation procedures in patients with non-resolving COVID-19-associated respiratory failure in the United States. We performed sm-FISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. We used a machine learning approach to project single cell RNA-Seq data from patients with late stage COVID-19 onto a single cell atlas of pulmonary fibrosis, revealing similarities across cell lineages. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.
2020-10-28 | GSE158127 | GEO
Project description:Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43-56 days) were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin), CD31, CD34, ?-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting ?-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.
| S-EPMC4305311 | biostudies-literature
Project description:The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle-the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness.
| S-EPMC8814827 | biostudies-literature
Project description:In the past few decades, studies on translation have converged towards the metaphor of a "ribosome nanomachine"; they also revealed intriguing ribosome properties challenging this view. Many studies have shown that to perform an accurate protein synthesis in a fluctuating cellular environment, ribosomes sense, transfer information and even make decisions. This complex "behaviour" that goes far beyond the skills of a simple mechanical machine has suggested that the ribosomal protein networks could play a role equivalent to nervous circuits at a molecular scale to enable information transfer and processing during translation. We analyse here the significance of this analogy and establish a preliminary link between two fields: ribosome structure-function studies and the analysis of information processing systems. This cross-disciplinary analysis opens new perspectives about the mechanisms of information transfer and processing in ribosomes and may provide new conceptual frameworks for the understanding of the behaviours of unicellular organisms.
| S-EPMC6627100 | biostudies-literature