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

Laing, A. G.; Lorenc, A.; Del Molino Del Barrio, I.; Das, A.; Fish, M.; Monin, L.; Munoz-Ruiz, M.; Mckenzie, D.; Hayday, T.; Francos Quijorna, I.; Kamdar, S.; Joseph, M.; Davies, D.; Davis, R.; Jennings, A.; Zlatareva, I.; Vantourout, P.; Wu, Y.; Sofra, V.; Cano, F.; Greco, M.; Theodoridis, E.; Freedman, J.; Gee, S.; Nuo En, Chan; J., Ryan; S., Bugallo Blanco; E., Peterson; P., Kisand; K., Haljasmagi; L., Martinez; L., Merrick; B., Bisnauthsing; K., Brooks; K., Ibrahim; M., Mason; J., Lopez Gomez; F., Babalola; K., Abdul- Jawad; S., Cason; J., Mant; C., Doores; K., Seow; J., Graham; C., di Ros

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.