Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-α, IL-6, IL-10, and IFN-γ levels in patients with Crimean-Congo hemorrhagic fever

• Published in: BMC infectious diseases Vol. 14; no. 1; p. 416
• Main Authors: Kaya, Safak, Elaldi, Nazif, Kubar, Ayhan, Gursoy, Nevcihan, Yilmaz, Meral, Karakus, Gulderen, Gunes, Turabi, Polat, Zubeyde, Gozel, Mustafa Gokhan, Engin, Aynur, Dokmetas, Ilyas, Bakir, Mehmet, Yilmaz, Neziha, Sencan, Mehmet
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 28-07-2014; BioMed Central
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Viral - blood; Cytokines - blood; Enzyme-Linked Immunosorbent Assay; Female; Hemorrhagic Fever Virus, Crimean-Congo - genetics; Hemorrhagic Fever Virus, Crimean-Congo - immunology; Hemorrhagic Fever Virus, Crimean-Congo - isolation & purification; Hemorrhagic Fever, Crimean - blood; Hemorrhagic Fever, Crimean - mortality; Hemorrhagic Fever, Crimean - virology; Humans; Immunoglobulin G - blood; Interleukin-10 - blood; Interleukin-6 - blood; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Tumor Necrosis Factor-alpha - blood
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/1471-2334-14-416

Although there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients.
In total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis.
The mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases.
The increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.