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

Abstract

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.

Longitudinal proteomic profiling reveals increased early inflammation and sustained apoptosis proteins in severe COVID-19

“…~10 days after initial symptom onset), but declined thereafter before patient discharge, with the possible exception of IL-6 which remained high in several ICU patients after an initial decrease (Fig 2A-C). As was recently noted 4 , the IL-6 -IL-10 -CXCL10 triad showed striking correlations with disease severity and the levels of these analytes were elevated in the great majority of hospitalized COVID19 patients, attesting to a highly in ammatory response to the virus.…”

“…Thus, most patients across a range of disease severities were reported to display a core peripheral blood immune signature, in essence comprising hyperactivation and severe depletion of selective CD4 + and CD8 + ab T cell subsets, Vg9Vd2 T cells, and NK cells; adaptive B cell responses; and profound alterations in the composition of the blood monocyte and dendritic cell compartments 4,5,6 . Within this signature, discrete components were associated with disease-severity 5 .…”

“…study was supported by the European Regional Development Fund (Project No 2014-2020. 4.01.15-0012 and the Centre of Excellence in Genomics (EXCEGEN) framework), the Estonian Research Council grants PUT1367 and PRG377.…”

Deciphering the state of immune silence in fatal COVID-19 patients

“…The contribution of host immune system in establishing the worse prognosis has been already con rmed by several clinical observations on SARS-CoV-2 and other SARSs-dependent diseases. Indeed, lymphopenia and release of pro-in ammatory cytokines such as CXCL10 (IP10), interleukin (IL)6, IL8, IL10, tumor necrosis factor (TNF)α and C-C motif chemokine ligand (CCL)2 are enlisted as hallmark of severe SARS-CoV2 infection and correlate with adverse clinical outcome [5][6][7]. Accordingly, among clinical parameters associated to critical outcome, multicenter analysis on hospitalized COVID-19 patients, established among clinical parameters associated to critical outcome not only age, co-morbidities and pre-existing diseases but also immune alterations such as an increased neutrophil to lymphocyte ratio [8], hinting that pathogenic disease characteristics of the disease are worsened in sub-optimally e cient and immune dysfunctional patients.…”

“…Severe COVID-19 patients display some shared features of sepsis, including secretion of in ammatory cytokines, neutrophil hyper-activation, reduced function of natural killer (NK) and dendritic cells (DC), altered monocyte activation and lymphopenia [7,17]. Several high dimensional phenotypic and molecular approaches were deployed in order to dissect the biology of virus-immune system interaction during COVID-19 pathogenesis [7,16,[18][19][20][21][22]. These analyses were performed on peripheral blood and peripheral blood mononuclear cells (PBMCs) isolated from patients with different disease severity.…”