Cytokine response in crimean‐congo hemorrhagic fever virus infection

Abstract

We described the predictive role of cytokines in fatality of Crimean Congo Hemorrhagic Fever Virus (CCHFV) infection by using daily clinical sera samples. Consequent serum samples of the selected patients in different severity groups and healthy controls were examined by using human cytokine 17-plex assay. We included 12 (23%) mild, 30 (58%) moderate, 10 (19%) severe patients, and 10 healthy volunteers. The mean age of the patients was 52 (sd 15), 52% were female. Forty-six patients (88%) received ribavirin. During disease course, the median levels of IL-6, IL-8, IL-10, IL-10/12, IFN-γ, MCP-1, and MIP-1b were found to be significantly higher among CCHF patients than the healthy controls. Within the first 5 days after onset of disease, among the fatal cases, the median levels of IL-6 and IL-8 were found to be significantly higher than the survived ones (Fig. 3), and MCP-1 was elevated among fatal cases, but statistical significance was not detected. In receiver operating characteristic (ROC) analysis, IL-8 (92%), IL-6 (92%), MCP-1 (79%) were found to be the most significant cytokines in predicting the fatality rates in the early period of the disease (5 days). IL-6 and IL-8 can predict the poor outcome, within the first 5 days of disease course. Elevated IL-6 and IL-8 levels within first 5 days could be used as prognostic markers.

Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in Ifnar-/- mice

“…Despite the known challenges in drawing comparisons, we observed several parallels between the responses we recorded in Ifnar -/mice and reports of severe human disease. Ifnar -/mice demonstrated increased levels of proinflammatory cytokines (IL-1β, IL-6, CXCL10, TNF-α), and the anti-inflammatory cytokine IL-10, all of which have been associated with fatal outcomes in humans [50][51][52]. Increased levels of murine CXCL1 and CXCL2, functional homologs of human IL-8, correlate with reports of IL-8 as a diagnostic marker for disease severity in humans [52].…”

“…Ifnar -/mice demonstrated increased levels of proinflammatory cytokines (IL-1β, IL-6, CXCL10, TNF-α), and the anti-inflammatory cytokine IL-10, all of which have been associated with fatal outcomes in humans [50][51][52]. Increased levels of murine CXCL1 and CXCL2, functional homologs of human IL-8, correlate with reports of IL-8 as a diagnostic marker for disease severity in humans [52]. Finally, changes in clinical chemistry and CBC values reported in humans as important diagnostic markers for predicting disease severity, including elevated AST and ALT, elevated neutrophils, and lymphopenia [1,17,53,54], were also seen in Ifnar -/mice as disease severity increased.…”

Crimean–Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures

“…IFN‐γ was similar between both groups (Kaya et al., ). A more recent student study similarly showed increased IL‐6 and TNF‐α in fatal cases ( n = 5) compared with non‐fatal cases ( n = 22), with IL‐8 being an additional marker for fatality (Ergönül et al., ).…”

The relationship with clinical course and prognosis of serum endothelin-1, angiopoietin-2, and tie-2 levels in Crimean-Congo hemorrhagic fever

“…The patients were divided into those with mild-moderate disease and those with severe disease according to the criteria defined by Swanepoel et al and the modified criteria recommended by Ergönül et al [7,8], as well as the clinical indicators of poor prognosis. Forty patients were included in the mild-moderate group, 16 patients in the severe group, and 4 patients in the fatal group.…”