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:The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from non-infected healthy controls. Additionally, low-density granulocytes (LDGs) from patients with severe COVID-19 were included to understand their unique role. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. LDGs from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. These findings underscore the crucial role of neutrophil inflammasomes in driving inflammation during severe COVID-19. The study provides insights into the pathological mechanisms of severe COVID-19 and highlights potential targets for therapeutic intervention.
Project description:It is known that about 60% of all human messenger RNAs (mRNAs) regulated by microRNAs, the role of mRNAs and microRNAs in the critically ill patients with Coronavirus Infection 2019 (COVID-19) is unknown. To evaluate mRNA and microRNA in whole blood of the critically ill patients with COVID-19 and to elucidate the pathogenesis of COVID-19 including the subsequent proteins profile following mRNA and microRNA integration analysis. RNA was extracted from the whole blood in 5 healthy controls and 10 critically ill patients with COVID-19 at the time of admission. mRNA and miRNA were measured by RNA sequence, and gene expression variation and pathway analysis were performed. As the IFNs proteins profile cohort, IFN-α2, IFN-β, IFN-γ, IL-27 and IFN-λ1 were measured on the day of admission (day 1, 181 critical and 22 non-critical patients) and day 6-8 (168 critical patients) in COVID19 patients and 19 healthy controls. Compared to healthy controls, 3488 mRNA and 31 miRNA genes were identified in the differentially expressed genes in the critically ill patients with COVID-19 (p-value<0.05, Log 2 fold change> |2|). In the canonical pathway analysis using Ingenuity Pathway Analysis (IPA), interferon signaling pathway was the most activated. In plasma interferon levels, IFN-β was elevated along with the increase of severity compared to healthy controls. IFN-λ1 was elevated in moderate disease compared to healthy controls, and conversely, IFN-λ1 was lower in severe disease than in moderate disease. Integration of mRNA and microRNA analysis showed activated interferon signaling. The plasma interferon proteins profile revealed that IFN-β (type I) and IFN-λ1 (type III) played an important role in the disease progression of COVID-19.
Project description:Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage and fatal outcomes. MicroRNAs (miRNAs) are detectable in blood, reflecting cell activation and tissue injury. We performed small RNA-Seq in healthy controls (N=11), non-severe (N=18) and severe (N=16) COVID-19 patients
Project description:To reveal genetic determinants of susceptibility to COVID-19 severity in the population and further explore potential immune-related factors, we performed a genome-wide association study on 284 confirmed COVID-19 patients (cases) and 95 healthy individuals (controls). We compared cases and controls of European (EUR) ancestry and African American (AFR) ancestry separately. To further exploring the linkage between HLA and COVID-19 severity, we applied fine-mapping analysis to dissect the HLA association with mild and severe cases.
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
