Project description:Although most SARS-CoV-2-infected individuals experience mild COVID-19, some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly upregulation of the TNF/IL-1beta-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1beta-driven inflammation, and this was not seen in patients with milder COVID-19 infection. Based on this, we propose that the type I IFN response exacerbates inflammation in patients with severe COVID-19 infection.
Project description:The adult data set. The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. A multiomics approach identified alterations in analytes associated with fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults.
Project description:Manuscript describes the daily dynamics of transcriptional responses in whole blood, from acute to convalescent phase, in severe and non-severe COVID-19 patients.
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:While critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during COVID-19 ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using scRNA-seq and plasma proteomics, we discovered that compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin (PG) signalling. Dexamethasone during severe COVID-19 depleted circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated gene, and activated IL1R2+ve neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils, preferential steroid-induced immature neutrophil expansion, and possibly different effects on outcome. Our single-cell atlas (www.biernaskielab.ca/COVID_neutrophil) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
Project description:The coronavirus pandemic (COVID-19) is associated with secondary bacterial and fungal infections globally. In India, inappropriate use of glucocorticoids, high prevalence of diabetes mellitus and a conducive environment for fungal growth are considered as the main factors for increased incidence of COVID-19 associated mucormycosis (CAM). Few cases of CAM without steroid abuse and normal blood glucose levels were also reported during the pandemic. This study was designed to explore whether altered immune responses due to severe COVID-19 infection predisposes towards development of mucormycosis. The global transcriptome profiling of monocytes and granulocytic cells derived from CAM, Mucormycosis, COVID-19 and healthy control groups were performed to identify the differentially expressed genes (DEGs) involved in dysregulated host immune response towards respective diseased and healthy conditions.
Project description:Many clinical risk factors for severe COVID-19, such as diabetes, hypertension, and high body mass index have been reported. However, searching for additional risk factors should be continued to predict the progression of severe COVID-19 more accurately. We suppose that clonal hematopoiesis of indeterminate potential (CHIP) can also be regarded as one of risk factors. To identify the influence of CHIP in COVID-19 pathogenesis, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from severe COVID-19 patient with CHIP and integrate the data with other published COVID-19 scRNA seq data (GSE149689). After clustering and annotating cell types, we compare the expression profiles between CHIP vs non-CHIP COVID-19 severe patient.
Project description:The clinical course of Coronavirus disease 2019 (COVID-19) displays a wide variability, ranging from completely asymptomatic forms to diseases associated with severe clinical outcomes. To reduce the incidence COVID-19 severe outcomes, innovative molecular biomarkers are needed to improve the stratification of patients at the highest risk of mortality and to better customize therapeutic strategies. MicroRNAs associated with COVID-19 outcomes could allow quantifying the risk of severe outcomes and developing models for predicting outcomes, thus helping to customize the most aggressive therapeutic strategies for each patient. Here, we analyzed the circulating miRNA profiles in a set of 12 hospitalized patients with severe COVID-19, with the aim to identify miRNAs associated with in-hospital mortality.