Rapid immune perturbations during sepsis and necrotising enterocolitis in preterm babies (preprint)

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.

A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis (preprint)

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.