The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes

Abstract

The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.

Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18–dependent activation

“…Although IL-12 was not detected in our CBA analyses, the physiological concentration may be below the limit of detection. Furthermore, Guo et al (28) reported that IL-18 (but not IL-12) was readily found in the serum of hospitalized H7N9 patients. Indeed, the fact that IL-18 is present at significant levels in the peripheral circulation suggests that a "global" activation of MAIT cells may occur in multiple peripheral sites in addition to the infected lung.…”

“…+ T cells at multiple time points after disease onset: days 6-12, days 13-20, and days [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] (Fig. 1B).…”

Risk of Severe Influenza Infection: Hypercytokinemia Gene Polymorphisms and Related Plasma Proteome in Canadian Young Adults

“…Previous studies have examined the proteomic profile associated with the response to IAV infection and the heritability of risk of severe disease in Mexican, Chinese, African and American Indigenous populations [13,[22][23][24][25]. However, studies comparing the association between variants in cytokine-coding genes and various proteome biomarkers of risk for severe infection are lacking in the general healthy population and in Canation and code for cytokine synthesis and proteomic biomarkers in a population of young Canadian adults.…”

C-C Motif Chemokine Ligand 2 (CCL2) Mediates Acute Lung Injury Induced by Lethal Influenza H7N9 Virus

“…Most infected patients have exhibited excessive cytokine and chemokine production, which could result in hypercytokinemia and is associated with disease severity (Chen et al, 2013; Chi et al, 2013; Huang et al, 2014; Guo et al, 2015). Hypercytokinemia, also known as a “cytokine storm,” is an early indicator of H7N9-induced ALI.…”

“…Previous studies have shown that CCL2 plays a crucial role in influenza virus H1N1 infection (Maelfait et al, 2016). Although increased expression of CCL2 during influenza infection has been well-documented (Zhou et al, 2013; Guo et al, 2015), the effects of the CCL2/CCR2 pathway on the pathogenesis of infection are controversial (Dawson et al, 2000; Narasaraju et al, 2010; Maelfait et al, 2016). Thus, we determined the effects of CCL2 on the severity of H7N9-induced ALI in an experimental mouse model.…”