Similar Datasets
Project description:Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multi-organ involvement in MIS-C encompassing diverse cell types including endothelial and neuronal cells, and an enrichment of pyroptosis related genes. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers.
2023-06-04 | GSE225222 | GEO
Project description:Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multi-organ involvement in MIS-C encompassing diverse cell types including endothelial and neuronal cells, and an enrichment of pyroptosis related genes. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers.
2023-06-04 | GSE225221 | GEO
Project description:Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multi-organ involvement in MIS-C encompassing diverse cell types including endothelial and neuronal cells, and an enrichment of pyroptosis related genes. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers.
2023-06-04 | GSE225220 | GEO
Project description:Background: COVID-19 has infected more than 100-million worldwide. Children appear less susceptible to COVID-19 and present with milder symptoms. Cases of children with COVID-19 developing clinical features of Kawasaki-disease have been described. Methods: We utilised SWATH-MS proteomics to determine the plasma proteins expressed in healthy children, children with multisystem inflammatory syndrome (MIS-C) and children with COVID-19 induced ARDS. Pathway analyses were performed to determine the affected pathways. Results: 76 proteins were differentially expressed across the groups, with 85 and 52 proteins specific to MIS-C and COVID-19 ARDS. Complement and coagulation activation were implicated in these clinical phenotypes, however there was contribution of FcGR and BCR activation in MIS-C and scavenging of heme and retinoid metabolism in COVID-19 ARDS. Conclusions: We show proteome differences in MIS-C and COVID-ARDS, although both show complement and coagulation dysregulation. The results may be helpful in developing therapeutic targets that could improve the outcomes for these children.
2022-04-06 | PXD025125 | Pride
Project description:Early prediction of COVID-19 in-hospital mortality relies usually on patients' preexisting comorbidities and is rarely reproducible in independent cohorts. We wanted to compare the role of routinely measured biomarkers of immunity, inflammation, and cellular damage with preexisting comorbidities in eight different machine-learning models to predict mortality, and evaluate their performance in an independent population. We recruited and followed-up consecutive adult patients with SARS-Cov-2 infection in two different Italian hospitals. We predicted 60-day mortality in one cohort (development dataset, n = 299 patients, of which 80% was allocated to the development dataset and 20% to the training set) and retested the models in the second cohort (external validation dataset, n = 402). Demographic, clinical, and laboratory features at admission, treatments and disease outcomes were significantly different between the two cohorts. Notably, significant differences were observed for %lymphocytes (p < 0.05), international-normalized-ratio (p < 0.01), platelets, alanine-aminotransferase, creatinine (all p < 0.001). The primary outcome (60-day mortality) was 29.10% (n = 87) in the development dataset, and 39.55% (n = 159) in the external validation dataset. The performance of the 8 tested models on the external validation dataset were similar to that of the holdout test dataset, indicating that the models capture the key predictors of mortality. The shap analysis in both datasets showed that age, immune features (%lymphocytes, platelets) and LDH substantially impacted on all models' predictions, while creatinine and CRP varied among the different models. The model with the better performance was model 8 (60-day mortality AUROC 0.83 ± 0.06 in holdout test set, 0.79 ± 0.02 in external validation dataset). The features that had the greatest impact on this model's prediction were age, LDH, platelets, and %lymphocytes, more than comorbidities or inflammation markers, and these findings were highly consistent in both datasets, likely reflecting the virus effect at the very beginning of the disease.
| S-EPMC8444380 | biostudies-literature
Project description:In early 2020, at the beginning of the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare cases were reported in children and adolescents of multisystem inflammatory syndrome in children (MIS-C). MIS-C is characterized by fever, systemic inflammation, and multiorgan dysfunction and usually presents late in SARS-CoV-2 infection. Since May 2020, the Centers for Disease Control and Prevention (CDC) has recorded all reported cases of COVID-19 and MIS-C in children and adolescents in the USA. In April 2021, the American College of Rheumatology (ACR) revised its clinical guidelines for diagnosing and managing hyperinflammation and MIS-C. There are several challenges ahead for preventing, diagnosing, and managing MIS-C, particularly following the rapid emergence of new strains of SARS-CoV-2. This Editorial aims to present an update on the current status of the clinical presentation, diagnosis, and management of MIS-C and includes some updates from population studies and clinical guidelines.
| S-EPMC8176784 | biostudies-literature
Project description:Reactive oxygen species (ROS) are generated after exposure to harmful environmental factors and during normal cellular metabolic processes. The balance of the generating and scavenging of ROS plays a significant role in living cells. The accumulation of ROS will lead to oxidative damage to biomolecules including nucleic acid. Although many types of oxidative nucleic acid damage products have been identified, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoG) has been commonly chosen as the biomarkers of oxidative damage to DNA and RNA, respectively. It has been demonstrated that oxidative damage to nucleic acid is an initiator in pathogenesis of numerous diseases. Thus, oxidative nucleic acid damage biomarkers have the potential to be utilized for detection of diseases. Herein, we reviewed the relationship of oxidative nucleic acid damage and development of various diseases including cancers (colorectal cancer, gastrointestinal cancer, breast cancer, lung cancer, epithelial ovarian carcinoma, esophageal squamous cell carcinoma), neurodegenerative disorders and chronic diseases (diabetes and its complications, cardiovascular diseases). The potential of oxidative nucleic acid damage biomarkers for detection of diseases and drug development were described. Moreover, the approaches for detection of these biomarkers were also summarized.
| S-EPMC5650463 | biostudies-literature
Project description:Purpose: This study aims to characterize the early innate and adaptive responses induced by SARS-CoV-2 infection in children and adults over time up to 8 weeks post symptoms onset (POS). We report the gene signature of COVID-19 over the course of the disease in both age groups. The kinetic of infection was divided in 5-time intervals according to the calculated days POS: interval 1 (0-5), interval 2 (6-14), interval 3 (15-22), interval 4 (23-35), and interval 5 (36-81). Methods: RNA extraction was performed automatically via the PAXgene Blood miRNA Kit and the QIAcube instrument (Qiagen) following the manufacturer’s protocol. RNA concentration and quality were assessed by using the Qubit instrument (Invitrogen) and the Agilent 2100 Bioanalyzer, respectively. The Stranded Total RNA Ribo-Zero Plus kit from Illumina was used for the library preparation with 100 ng of total RNA as input. Library molarity and quality were assessed with the Qubit and Tapestation using a DNA High sensitivity chip (Agilent Technologies). Libraries were pooled at 2 nM for clustering and sequenced on an Illumina HiSeq 4000 sequencer for a minimum of 30 million single-end 100 reads per sample. Main results: (I) we observed an antiviral-IFN-signature and innate-cell-activation within the first 5 days post symptoms onset (POS), while genes associated with CD4 T-cell responses, plasma cells and immunoglobulin were upregulated in both age groups during the first two weeks POS, indicative of SARS-CoV-2-specific adaptive immune responses; (II) in adults, genes associated with IFN antiviral responses and activated dendritic cells were maintained during the second week of disease, and subsided only after 14 days. By contrast, those transcriptome changes subsided already after 5 days in children.
2021-09-22 | GSE166190 | GEO
Project description:While SARS-CoV-2 infection results in a mild disease course for most children, severe manifestations including respiratory failure and a Multisystem Inflammatory Syndrome in Children (MIS-C) can develop in rare cases. Here, we present a longitudinal immune profiling study of children who developed SARS-CoV-2-associated MIS-C during acute disease and following recovery, relative to children with more typical clinical manifestations of SARS-CoV-2 infection. We demonstrate distinct immune parameters associated with acute MIS-C including elevated levels of pro-inflammatory cytokines in circulation not observed in children with acute COVID-19 (non-MIS-C), aberrant expression of activation and tissue residency signatures by T cells, and expansion of T cells bearing specific TCR chains. Importantly, markers of tissue-derived T cells correlated with clinical measurements of cardiac damage suggesting key roles for T cells in the disease process. While these T cell alterations and the accompanying systemic inflammation resolved during recovery, children with prior MIS-C generated increased frequencies of functionally robust virus-specific T cells compared to children who recovered from mild disease, while both cohorts generated protective, long-lasting SARS-CoV-2-specific antibodies. Together our results reveal that the T cell response in acute MIS-C contributed to disease pathology, while also generating robust memory responses for future immune protection.
2023-04-10 | GSE213192 | GEO
Project description:Background/purposeThe association between dysregulated innate immune responses seen in Kawasaki disease (KD) with predisposition to Kawasaki-like multisystem inflammatory syndrome in children (MIS-C) remains unclear. We aimed to compare the innate immunity transcriptome signature between COVID-19 and KD, and to analyze the interactions of these molecules with genes known to predispose to KD.MethodsTranscriptome datasets of COVID-19 and KD cohorts (E-MTAB-9357, GSE-63881, GSE-68004) were downloaded from ArrayExpress for innate immune response analyses. Network analysis was used to determine enriched pathways of interactions.ResultsUpregulations of IRAK4, IFI16, STING, STAT3, PYCARD, CASP1, IFNAR1 and CD14 genes were observed in blood cells of acute SARS-CoV-2 infections with moderate severity. In the same patient group, increased expressions of TLR2, TLR7, IRF3, and CD36 were also noted in blood drawn a few days after COVID-19 diagnosis. Elevated blood PYCARD level was associated with severe COVID-19 in adults. Similar gene expression signature except differences in TLR8, NLRP3, STING and IRF3 levels was detected in KD samples. Network analysis on innate immune genes and genes associated with KD susceptibility identified enriched pathways of interactions. Furthermore, higher expression levels of KD susceptibility genes HLA-DOB, PELI1 and FCGR2A correlated with COVID-19 of different severities.ConclusionOur findings suggest that most enriched innate immune response pathways were shared between transcriptomes of KD and COVID-19 with moderate severity. Genetic polymorphisms associated with innate immune dysregulation and KD susceptibility, together with variants in STING and STAT3, might predict COVID-19 severity and potentially susceptibility to COVID-19 related MIS-C.
| S-EPMC8214167 | biostudies-literature