N the fatal group

N the fatal group 4CzIPN might have occurred due to inappropriate immune response both in the early and late phase of the disease in these cases. Innate immunity is the first line of bmjopen-2016-011824 defense against viruses before adaptive immunity develops and it is characterized by the production of type I IFN, which is crucial for limiting the early replication and spread of viruses. CCHFV is one of the viruses sensitive to type I IFN, and it delays the IFN response [33]. Furthermore, CCHFV challenge of type I IFN receptor-knockout mice results in a fatal outcome and higher CCHFV titers [34,35]. This study showed that all survivors develop a sufficient amount of specific IgG antibody after 8 days of fever onset. Due to the limitation in serum sample amounts, we could not estimate IgG antibody levels in the fatal patients after day 9 of the illness. However, when compared to survivors, the consistently higher CCHFV titer in a fatal CCHF patient after day 8 of the illness strongly suggests insufficient amount of specific IgG antibody against the virus. The initial virus specific antibody activity can be assessed by ELISA IgG and IgM after 2 days of the onset of CCHF symptoms and the levels increase between days 7 to 9 of the illness in survivors [20]. Likewise Duh, et al. [13] showed that all 9 fatal and most of the severe CCHF cases had no IgG antibodies as determined by ELISA even on day 9 of the illness. Other reports also suggest insufficient IgG antibody responses in severe and fatal CCHF cases [15,20,23]. The lack of specific IgG antibodies in fatal cases has entailed using human CCHF hyperimmunoglobulin with a promising effect [16]. Finding a meaningful correlation between serum CCHFV titer and DIC score can be expected because the results of this study, as well as earlier ones, suggest a close relationship between CCHFV titer, and both clinical severity and fatal outcome in CCHF [11,13-16].Conclusion In conclusion, the results of this study showed that higher CCHFV titers and overproduction of TNF- and IL-6, (a phenomenon called cytokine storm), the presence of DIC, and the absence of CCHFV specific immunity have important roles in the pathogenesis of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13485127 CCHF and are strongly associated with a fatal outcome. In addition, the levels of serum IL-6, TNF-, and CCHFV titers correlated with the existence of DIC, subsequently leading to hemorrhages and death. Lower serum CCHFV titers in the survivors than in the fatal patients during the course of CCHF may suggest that the disease is being controlled both in the acute and convalescent phases by the innate and adaptive immune systems. The difference between innate and adaptive immune 3-Fluoro-2-(trifluoromethyl)aniline responses of the survivor and fatal CCHF patients need to be elucidated to understand thoroughly the pathogenesis of CCHF. Additional filesAdditional file 1: Correlation between serum interleukin-6 level (pg/mL) at the time of admission and (A) C-reactive protein, (B) Prothrombin time (C), Activated partial thromboplastin time, (D) International normalized ratio, (E) Disseminated intravascular coagulation score, (F) Tumor necrosis factor-alpha, and (G) Aspartate aminotransferase. Additional file 2: Correlation between serum virus titer (copy/mL) at the time of admission and (A) C-reactive protein, (B) Prothrombin time (C), Activated partial thromboplastin time, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/22763976 (D) International normalized ratio, (E) Disseminated intravascular coagulation score, (F) Serum tumor necrosis factor-alpha, and (G) serum interleukin-6.Competing interest Th.