title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Infectious Diseases and Clinical Bacteriology, Training and Research Hospital, Diyarbakir, Turkey. ksafak76@gmail.com.
authors: Safak
authors: S
authors: Kaya
authors: Nazif
authors: N
authors: Elaldi
authors: Ayhan
authors: A
authors: Kubar
authors: Nevcihan
authors: N
authors: Gursoy
authors: Meral
authors: M
authors: Yilmaz
authors: Gulderen
authors: G
authors: Karakus
authors: Turabi
authors: T
authors: Gunes
authors: Zubeyde
authors: Z
authors: Polat
authors: Mustafa Gokhan
authors: MG
authors: Gozel
authors: Aynur
authors: A
authors: Engin
authors: Ilyas
authors: I
authors: Dokmetas
authors: Mehmet
authors: M
authors: Bakir
authors: Neziha
authors: N
authors: Yilmaz
authors: Mehmet
authors: M
authors: Sencan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D006479:Hemorrhagic Fever, Crimean / Q000097:blood* / Q000401:mortality / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10