ABSTRACT
Deaths complicated by infection are a major cause of mortality in preterm babies. Here we study the influence of bacterial sepsis and the gut inflammatory disorder necrotising enterocolitis (NEC), frequently associated with bacterial complications, on host immune dysregulation in extremely preterm babies. We identify a peripheral blood immune signature that distinguishes sepsis and NEC from other cases of suspected, though microbiologically unconfirmed, sepsis. Some signature traits could even make this distinction in babies with low or undetectable C-reactive protein, a common clinical test to alert infection. Our analysis incorporates longitudinal single-cell genomic evaluation of peripheral blood immune cells, elucidating amphiregulin as a key differentially expressed gene during sepsis and NEC, which was validated as a plasma analyte that correlated with disease-associated clinical signs. Collectively, signature immune traits provide insight into dysregulated sepsis and NEC-associated pathways and highlight candidate markers, pending validation, that could improve diagnostic-led, targeted antibiotic prescribing.
Subject(s)
EnterocolitisABSTRACT
Person-to-person transmission of SARS-CoV-2 virus has triggered a global emergency because of its potential to cause life-threatening Covid-19 disease. By comparison to pauci-symptomatic virus clearance by most individuals, Covid-19 has been proposed to reflect insufficient and/or pathologically exaggerated immune responses. Here we identify a consensus peripheral blood immune signature across 63 hospital-treated Covid-19 patients who were otherwise highly heterogeneous. The core signature conspicuously blended adaptive B cell responses typical of virus infection or vaccination with discrete traits hitherto associated with sepsis, including monocyte and dendritic cell dampening, and hyperactivation and depletion of discrete T cell subsets. This blending of immuno-protective and immuno-pathogenic potentials was exemplified by near-universal CXCL10/IP10 upregulation, as occurred in SARS1 and MERS. Moreover, specific parameters including CXCL10/IP10 over-expression, T cell proliferation, and basophil and plasmacytoid dendritic cell depletion correlated, often prognostically, with Covid-19 progression, collectively composing a resource to inform SARS-CoV-2 pathobiology and risk-based patient stratification.
Subject(s)
COVID-19 , Sepsis , Tumor Virus InfectionsABSTRACT
A new beta Coronavirus (SARS-CoV-2) infection was first identified in the Wuhan City, China in December 2019 and after that it had spread rapidly throughout the globe and subsequently WHO have announced it as a pandemic. So, SARS-CoV-2 has now become a global threat to human civilization. Recent studies showed that the proteomic data of SARS-CoV-2 is closely related with other beta Coronavirus. The phylogenetic tree revealed the closeness of recently reported SAR-CoV2 with SARS-CoV by using MEGA 7 along with the suitable protocol of Neighbor joining algorithm. The spike glycoprotein plays the most important role during the onset of infection. Several mutations have been reported across the globe in the S Proteins. In this research, molecular docking between the SARS-CoV-2 spike glycoprotein and ACE2 protein was carried out in PatchDock web servers. WEBnm@ calculated the molecular simulation using Normal Mode Analysis (NMA) along with lowest deformation energy value which signifies the domain motions. Also during multiple sequence analysis, variations were observed within the Spike protein reported globally. 3- Dimensional structure of protein molecules were designed using homology modeling and the structure were validated through Q mean score and Ramachandran plot. All of the designed sequences were having around 91% of the amino acid in the favored region of Ramachandran plot. In order to check the binding affinity difference between the mutated and non-mutated strains, the generated models were docked with human ACE2 molecules. The non mutated strains have given the similar ACE value. However, there were variations in ACE value of the mutated strains. This observation provides evidence of Phylogenetic diversity and evolution.