Project description:The SARS-CoV-2 pandemic has led to increasing numbers of COVID-19 patients all over the world. Aetiopathologies range from no symptoms, mild flu-like to severe cases succumbing to respiratory failure. Reports on a dysregulated immune system in the severe cases, showing similarities to cytokine release syndrome, calls for better characterization and understanding of the changes in the immune system as well as their variance across COVID-19 patients in order to be able to design according to host-directed therapies. Here, we profiled blood transcriptomes of 39 COVID-19 patients and 10 control donors. Enriched granulocyte signatures in whole blood samples were verified in granulocyte samples from 49 COVID-19 patients in a second cohort.
Project description:In this study, we sought to identify circulating microRNA (miRNA) signatures associated with COVID-19 severity and outcome through small RNA-sequencing of serum samples from 89 COVID-19 patients and 45 healthy controls. As results, a set of miRNAs associated with lung disease, vascular damage and inflammation were upregulated in serum of COVID-19 patients vs controls, while miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis and stress response were downregulated. In addition, patients with severe COVID-19 vs mild or moderate disease had a circulating miRNA signature associated with sepsis, hearth failure, tissue fibrosis, inflammation, and impairment of type I IFN and antiviral responses. A subset of the differentially expressed miRNAs predicted ICU admission, sequelae and mortality in COVID-19 patients. Investigation of the differentially expressed circulating miRNAs in relevant human cell types in vitro showed that some of these miRNAs were modulated directly by SARS-CoV-2 infection or indirectly by type I IFN stimulation.
Project description:SARS-CoV-2 is an emerging mosquito-borne pathogen with increasing public health significance. To characterize interconnected immune responses to SARS-CoV-2, we here examined transcriptional signatures of CD4 and CD8 T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with naturally-acquired SARS-CoV-2 infection. Whole transcriptome analysis demonstrated that all seven immune cells among PBMCs were clustered together with disease severity regardless of cell types. mDCs and pDCs gene signatures distinct disease severity. A distinct phenotype was observed in severe patients with or without plasma viremia, demonstrating a highly impaired induction of Interferon stimulated genes (ISGs) accompanied by imbalanced type I interferon sensing and an excessive inflammatory response. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in blood from different disease severe COVID-19 patients.