ABSTRACT
BACKGROUND AND AIM: The ideal biomarker(s) to track evolution and the underlying basis of sepsis remain elusive. We hypothesized that assessing differential mRNA gene expression may aid in tracking sepsis pathogenesis in infants with meningococcal septic shock (MSS). METHOD(S): Temporal paediatric gene expression datasets from Meningococcal Group B sepsis studies in the United Kingdom (MSS1, 29 samples) and Holland (MSS2, 41 samples) underwent Principal Component Analysis (PCA) and Gene Set Enrichment Analysis (GSEA). RESULT(S): Gene-expression clustering algorithm for both datasets demonstrated a baseline state on admission, an intermediate state, and a final state. Additionally, PCA plots suggested a gene-expression trajectory. The MSS1 study showed that 410 genes differentiated survivors from a nonsurvivor, including the ICAM-3 gene. Moreover GSEA t-Test identified apoptosis to be significantly differently (p = 0.02 and q = 0.15) associated with the fatal case compared to the four survivors in MSS1. Also in MSS1, we identified a genesignature for cytokine production which included 5 genes (CLC, HFE, HLA-F, NLRP3, TNFRSF1B) from the cytokine GSEA gene panel. The genes NLRP3 and TNFRSF1B have been noted in the cytokine storm of Coronavirus infection. Also Transcript Time Course Analysis (TTCA) confirmed differential gene function associated with Coronavirus. CONCLUSION(S): Transcriptomic analysis in two independent datasets in infants with MSS identified a trajectorial pattern. Further, the transcriptome expression differed between survivors and non-survivors, suggesting differences in cytokine signalling. Including the existence of genes associated with the cytokine storm of SARS-CoV2. The exploitability of transcriptome analysis to guide therapy and prognosis requires further investigation. (Figure Presented).
ABSTRACT
BACKGROUND AND AIM: Increased Vascular Endothelial Growth Factor (VEGFA) Gene Expression (GE) has been documented in SARS-CoV2 infection. We wished to understand the relationship of VEGFA and VEGF B GE in both Murine SARS-CoV and Human SARS-CoV-2 in-vitro models of infection. METHOD(S): Secondary analysis of datasets from mice given nasal installation of SARS-CoV (MA15), MS1 (GSE33266MCV-1) and MS2 (GSE68820) from pulmonary tissues was undertaken. This allowed viral dose and temporal response analysis, respectively. Also studied were In-vitro Human hACE2 cells infected with SARS-CoV2 (dataset INV, GSE169158). Gene expression (GE) VEGF sub-types were analysed using Qlucore Omics Explorer (QOE) and gene enrichment functional profiling through the g:Profiler online platform. RESULT(S): For Murine studies, MA15 instillation compared to controls in MS1, lead to down-regulation of both VEGFB (MA15 10