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Crimean Congo hemorrhagic fever (CCHF) is an acute viral infection that can cause death. The detection of host transcriptome is important for understanding differences in the pathogenesis of the disease. Long noncoding RNAs (lncRNAs) regulate gene expression in different biological processes. They have also emerged as key molecules for therapeutic targets. We investigated the lncRNA gene expression profiles by utilizing the microarray for the first time in CCHF. LncRNAs were determined by the comparisons between case-control, fatal case-control, and fatal case-nonfatal cases. Quantitative polymerase chain reaction was applied to validate the microarray results of some lncRNAs. In our study, 39 lncRNAs (5 downregulated and 34 upregulated) were found to be significantly regulated in the cases when compared to the controls (p < 0.05; FC ≥ 2). One hundred ten lncRNAs exhibited a statistically significant difference between fatal cases and controls. FER1L4, ECRP, and LOC100133669 are important lncRNAs in both case and fatal case groups compared with controls. These lncRNAs may be considered important therapeutic targets for the CCHF in further studies., (© 2022 Wiley Periodicals LLC.)

We aimed to decide which scoring system is the best for the evaluation of the course of Crimean-Congo Hemorrhagic Fever (CCHF) by comparing scoring systems such as qSOFA (quick Sequential Organ Failure Assessment), SOFA (Sequential Organ Failure Assessment), APACHE II (Acute Physiology and Chronic Health Evaluation II) and SGS (Severity Grading System) in centers where patients with CCHF were monitored. The study was conducted with patients diagnosed with CCHF in five different centers where the disease was encountered most commonly. Patients having proven PCR and/or IgM positivity for CCHF were included in the study. The scores of the scoring systems on admission, at the 72 nd hour and at the 120 th hour were calculated and evaluated. The data of 388 patients were obtained from five centers and evaluated. SGS, SOFA and APACHE II were the best scoring systems in predicting mortality on admission. All scoring systems were significant in predicting mortality at the 72 nd and 120 th hours. On admission, there was a correlation between the qSOFA, SOFA and APACHE II scores and the SGS scores in the group of survivors. All scoring systems had a positive correlation in the same direction. The correlation coefficients were strong for qSOFA and SOFA, but poor for APACHE II. A one-unit rise in SGS increased the probability of death by 12.818 times. qSOFA did not provide significant results in predicting mortality on admission. SGS, SOFA and APACHE II performed best at admission and at the 72 nd and 120 th hours.

Crimean Congo hemorrhagic fever (CCHF) is one of the most important viral infections and is caused by Crimean Congo hemorrhagic fever orthonairovirus (CCHFV). Severity of CCHF can vary from a mild and nonspecific illness to a severe disease with fatal outcomes. MicroRNAs (miRNAs) have an increasing impact on the different pathways of viral infections. Within the transition process from acute phase to convalescence with 18 CCHF patients, we investigated the impacts on miRNA via microarray for the first time. We also compared miRNA gene expression in 16 severe and 15 mild cases. We identified Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways associated with significant miRNAs utilizing DIANA TOOLS mirPath v.3. In this study, miR-15b-5p and miR-29a-3p were significantly downregulated in statistical terms; miR-4741, miR-937-5p, miR-6068, miR-7110-5p, miR-6126, and miR-7107-5p were upregulated in acute cases in comparison with convalescent patients (p ≤ .05). In total, 28 miRNAs (8 downregulated, 20 upregulated) were differentially expressed in severe CCHF patients as compared with mild cases (p ≤ .05). Whereas miR-6732-3p, miR-4436b-5p, miR-483-3p, and miR-6807-5p had the highest downregulation, miR-532-5p, miR-142-5p, miR-29c-3p, and let-7f-5p had the highest upregulation in severe patients in comparison with mild cases. Consequently, we determined that CCHF-induced miRNAs are associated with antiviral and proinflammatory pathways in acute and severe cases. In comparison with convalescence, these miRNAs in acute period may be therapeutic targets., (© 2021 Wiley Periodicals LLC.)

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single-stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus-host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case-control, fatal-control, and fatal-nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy-five and sixty-six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case-control, fatal-control, and fatal-nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir-based therapy against CCHF using miRNAs in the future., (© 2019 Wiley Periodicals, Inc.)

Crimean-Congo Hemorrhagic Fever (CCHF) is an acute viral hemorrhagic disease. In this study, an evaluation was made of the potential use of iron metabolism and liver function biomarkers to estimate the bleeding status in CCHF patients. This prospective study was conducted in Cumhuriyet University, Turkey. Only patients with confirmed CCHF were enrolled in the study. The study subjects comprised 40 CCHF patients and 37 healthy control subjects. Serum iron, unsaturated iron binding capacity (UIBC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were determined using the colorimetric method. Serum ferritin levels were measured using the electrochemiluminescent method. The serum ferritin (p = 0.037), AST (p = 0.0002), ALT (p = 0.002), LDH (p = 0.0005) and aPTT (p = 0.001) values were higher in patients with bleeding than in patients without bleeding. Receiving operating characteristic analyses were applied for the area under the curve (AUC) values for ferritin, aPTT, and AST to discriminate the bleeding status in patients, an these were determined as 0.717, 0.819, and 0.882, respectively. A cut-off value of 149 U/L for AST was obtained to discriminate the bleeding condition in CCHF patients. Higher ferritin (p < 0.0001) levels were determined in patients compared to the control group. The iron (p = 0.180) and UIBC (p = 0.0017) values were lower in patients than in the control group. Cytokine storm due to an increase in ferritin levels may contribute to the increased inflammation and coagulation abnormalities in CCHF patients. It was concluded that routine screening of the AST level would be helpful to estimate the bleeding status in addition to screening liver damage in CCHF patients., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Crimean-Congo hemorrhagic fever (CCHF) is a viral infection. Circulating plasma cell-free DNA (pcf-DNA) is a novel marker indicating cellular damage. So far, the role of pcf-DNA did not investigate in CCHF patients. In the current study, pcf-DNA levels were investigated in CCHF patients with different clinical severity grades to explore the relationship between circulating pcf-DNA level, virus load, and disease severity. Seventy-two patients were categorized as mild, intermediate, and severe based on severity grading scores. The pcf-DNA level was obtained from all participants on admission and from the survivors on the day of the discharge. The controls consisted of 31 healthy. Although the pcf-DNA level at admission was higher in patients than in the controls, the difference was not statistically significant (P = 0.291). However, at admission and in the convalescent period, the difference between pcf-DNA levels in mild, intermediate, and severe patient groups was significant. The pcf-DNA level in severe patients was higher than in the others. Furthermore, compared to survivors, non-survivors had higher pcf-DNA levels at admission (P = 0.001). A direct relationship was found between the pcf-DNA level and the viral load on the day of discharge in surviving patients. ROC curve analysis identified a pcf-DNA level of 0.42 as the optimal cut-off for prediction of mortality. The positive predictive value, negative predictive value, specificity, and sensitivity for predicting mortality was 100%, 72%, 100%, and 79%, respectively. In summary, our findings revealed that pcf-DNA levels may be used as a biomarker in predicting CHHF prognosis., (© 2015 Wiley Periodicals, Inc.)

We investigated the possibility of transmission of Crimean-Congo hemorrhagic fever (CCHF) virus through respiratory and physical contact. In this prospective study, we traced 116 close relatives of confirmed CCHF cases who were in close contact with the patients during the acute phase of the infection and evaluated the type of contact between patients and their relatives. These relatives were followed for clinical signs or symptoms indicative of CCHF disease, blood samples of those with and without clinical signs were analyzed for CCHF virus immunoglobulin M and G (IgM and IgG, respectively) by enzyme-linked immunosorbent assay. No close relatives developed any signs or symptoms of CCHF and were negative for CCHF virus IgM and IgG. The results suggest that CCHF virus is not easily transmitted from person to person through respiratory or physical contact.

Objectives: The Crimean-Congo hemorrhagic fever (CCHF) virus can spread from person to person and may cause nosocomial outbreaks among healthcare workers (HCWs). The US Centers for Disease Control and Prevention have recommended the use of personal protective equipment (PPE). We investigated the compliance of HCWs with PPE usage during the follow-up of patients, and also the number of risky contacts that occurred between patients and HCWs. We also aimed to determine the seroprevalence of CCHF virus in HCWs., Methods: This study was conducted at Cumhuriyet University Education and Research Hospital, a medical center located in a highly endemic area for CCHF where a total of 1284 confirmed CCHF patients were followed-up between 2002 and 2012. All HCWs who were at risk of CCHF virus contact and infection were included in the study. The compliance of the HCWs with PPE usage and the number of contacts that had occurred were recorded. HCW serum samples were analyzed for CCHF virus IgM and IgG by ELISA., Results: The total rates of PPE usage were 93.7% for gowns, 77.4% for gloves, and 38.9% for masks; the highest compliance was detected in the infectious diseases ward: 100%, 88.6%, and 82.9%, respectively. A total of four HCWs had a history of high-risk contact with contaminated material (two percutaneous exposure and two mucosal contacts), but the number of low-risk contacts was quite high. The total seroprevalence rate was only 0.53%., Conclusions: Although the HCWs at our medical center have dealt with an extremely high number of CCHF patients during the last decade, the total seropositivity for CCHFV IgG was only 0.53%. This low rate may be a result of high compliance with PPE usage and also regular education programs., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To describe ocular findings of patients with Crimean-Congo hemorrhagic fever (CCHF)., Design: Prospective, interventional, consecutive case series., Methods: This study was conducted in Sivas, a city located in the central Anatolia, between July 1 and August 31, 2007. Confirmed CCHF patients were enrolled in the study and underwent ocular examination during hospitalization., Results: Nineteen confirmed CCHF patients were included in this study. All patients were classified into 2 groups in terms of disease severity (severe vs nonsevere), according to the Swanepoel predictive criteria. Fourteen patients (73.7%) were classified as "nonsevere," and the remaining 5 patients (26.3%) were classified as "severe" in this study. One patient having severe disease died. Ocular findings were present in 14 patients (73.7%) and none of the patients presented any visual complaints. Ocular examination revealed that 7 patients (36.8%) had only bilateral multiple subconjunctival hemorrhage, and 2 patients (10.5%) (1 bilateral, 1 unilateral) had retinal hemorrhage. Five patients (26.3%) had subconjunctival hemorrhage and retinal hemorrhage. Follow-up examination 1 month later showed complete resorption of the subconjunctival hemorrhage and retinal hemorrhage. There was a statistically significant difference between patients with ocular findings and patients without ocular findings for prothrombin time (P = .011). There was no evidence of uveitis, retinal edema, sheathing of retinal vessels, or intravitreal hemorrhage in our patients., Conclusion: From the small sample study, CCHF caused a mild form of ocular disease. CCHF must be considered when subconjunctival or superficial retinal hemorrhages are seen in association with fever in endemic areas.

In the Tokat and Sivas provinces of Turkey, the overall Crimean-Congo hemorrhagic fever virus (CCHFV) seroprevalence was 12.8% among 782 members of a high-risk population. CCHFV seroprevalence was associated with history of tick bite or tick removal from animals, employment in animal husbandry or farming, and being >40 years of age.

Objective: The aim of this study was to evaluate the efficacy of oral ribavirin treatment in patients with Crimean-Congo haemorrhagic fever (CCHF)., Methods: In 2004, all patients diagnosed with CCHF were treated with oral ribavirin, however in 2003 none of the CCHF patients had been given treatment due to lack of confirmatory diagnostic information at that time in Turkey. In this study, patients treated with ribavirin in 2004 (n=126) were compared with ribavirin-untreated CCHF patients (n=92) in 2003. Patients only with a definitive diagnosis of CCHF (clinical symptoms plus the presence of specific IgM antibodies against CCHF virus and presence of viral antigen) were included in this study., Results: There was no difference in the case-fatality rate between treated and untreated patients (7.1% vs. 11.9%; P>0.05). A Cox Proportional Hazards regression analysis revealed that altered sensorium and prolonged international normalized ratio were independent predictors of mortality., Conclusion: Our results showed that oral ribavirin treatment did not improve the survival rate in CCHF patients. Ribavirin and supportive care are the only available choices for treatment of CCHF patients, but to ascertain the efficacy of ribavirin, more laboratory and observational studies are necessary and ultimately, to elucidate these conflicting results and evaluate the efficacy undoubtedly, a multicenter randomised controlled trial will be needed.