Project description:Red blood cells (RBC) depleted whole blood from COVID-19 patients and controls was harvested and processed in order to performed 10X single cell RNA-seq. For COVID-19 patients 2 samples 10 days a part were analyzed.
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. The majority of causative variants lie in regulatory elements that are located some distance from their target genes. High resolution chromosome conformation capture (3C) has proven useful for identifying enhancer-promoter interaction. We employed targeted Capture-C at loci with GWAS for severe COVID-19, Type-1 Diabetes (T1D), Ankylosing spondylitis (AS) and red blood cell traits (RBC)
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.
Project description:The objective of this experiment was to compare the transcriptomic profile (NanoString platform) of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild disease, and patients with severe COVID-19 with and without dexamethasone treatment, and healthy controls. We analyzed PBMCs from 4 mild COVID patients, 3 severe COVID patients,4 severe COVID patients treated with dexamethasone, and 5 healthy controls
Project description:Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA-Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups.
Project description:High throughput sequencing is performed on mRNA isolated from whole blood of adult Covid-19 patients, bacterial coinfection with Covid-19 and healthy controls in a South Indian cohort. Samples were collected from individuals at the time of hospitalization or visit to clinic. The Covid-19 samples are categorized by severeity.
Project description:The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is
primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport
oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients.
The present study combines state-of-the-art metabolomics, proteomics, and lipidomics
approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29
molecularly-diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of
glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and
the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also
observed, especially short and medium chain saturated fatty acids, acyl-carnitines, and sphingolipids.
Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count,
hematocrit, and mean corpuscular hemoglobin concentration, with only minor increases in mean
corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2
infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC
glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to offload
oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to
counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes
deoxyhemoglobin and finely tunes oxygen off-loading and metabolic rewiring towards the hexose
monophosphate shunt, RBCs from COVID-19 patients may be less capable to respond to
environmental variations in hemoglobin oxygen saturation/oxidant stress when traveling from the
lungs to peripheral capillaries and vice versa.
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to coronavirus disease 2019 (Covid-19) which has caused worldwide pandemic infection. Yet due to unknown reason, certain COVID-19 patients exhibit severe inflammatory reactions associated with cytokine storm and neutrophil infiltration and neutrophil extracellular traps (NETs) in the lung, leading to further complications of SARS-CoV-2 infection. To find out whether the cause of lung injury in COVID-19 patients is due to increased reactive oxygen species and subsequently NET formation we have compared the post-mortem lung biopsies of deceased COVID-19 patients to normal lung tissues using RNA-Seq analysis.
Project description:In this prospective observational cohort study, we found transcriptional evidence that persistent immune dysfunction was associated with 28-day mortality in both COVID-19 and non-COVID-19 septic patients. COVID-19 patients had an early antiviral response but became indistinguishable on a gene expression level from non-COVID-19 sepsis patients a week later. Early treatment of COVID-19 and non-COVID-19 sepsis ICU patients should focus on pathogen control, but both patient groups also require novel immunomodulatory treatments, particularly later during ICU hospitalization, independent of admission diagnosis. Some T1 samples were uploaded in GSE185263 and were not re-uploaded in this series.
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).