The Role of Blood Urea Nitrogen and C-Reactive Protein and Their Ratios to Albumin in Predicting Mortality in Crimean-Congo Hemorrhagic Fever

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is an acute febrile hemorrhagic disease that can be fatal. Almost one-eighth of people infected with CCHF develop serious illness. The mortality rate is high due to severe bleeding, diffuse intravascular coagulation, shock, and multiple organ failure. Early detection of serious illness can play a key role in developing effective treatment and follow-up strategies. C-reactive protein (CRP), blood urea nitrogen (BUN), and albumin have previously been evaluated as markers of clinical severity in infectious diseases. This study aimed to evaluate the role of these readily available and inexpensive biomarkers and their ratios as predictors of mortality risk in patients with CCHF. This retrospective observational single-center study was conducted between May and October 2022 in a regional hospital in northeastern Türkiye, where the incidence of CCHF is the highest. Hundred and fifty patients aged 18 years and over with a definitive diagnosis of CCHF were included; patients with chronic kidney disease requiring long-term hemodialysis and those with missing data were excluded from the study. The patients' demographic characteristics, comorbidities, initial complaints, and epidemiological, clinical, and laboratory findings were recorded. Receiver operating characteristics (ROC) curve analysis was used to determine the predictive power of the studied biomarkers. Categorical and continuous variables found to be significant for mortality were evaluated using univariate logistic regression. Variables found to be significant in this test were used to create a multivariate logistic regression model to identify independent risk factors for mortality. The median age of the patients was 49 (18-89) years and 93 (62.0%) were men. Twelve patients (8.0%) required intensive care and 11 (7.3%) died. Complaints of abdominal pain (p= 0.010), hypotension (p= 0.002), somnolence (p< 0.001), and bleeding (p< 0.001) at the time of hospital admission were significantly more common among non-surviving patients. BUN and CRP were the biomarkers with the highest diagnostic power for mortality. A BUN cut-off value of 19.5 mg/dl had 100% sensitivity and 74.1% specificity, while a CRP cut-off value of 31.5 mg/L had 100% sensitivity and 81.8% specificity. CRP/albumin ratio (CAR) and BUN/albumin ratio (BAR) had higher predictive power than all individual biomarkers. At a cut-off point of 0.98, CAR had diagnostic power of 0.942 (95% confidence interval= 0.901-0.984), 100% sensitivity, and 84.9% specificity for mortality. At a cut-off of 0.50, BAR predicted mortality with diagnostic power of 0.932 (95% confidence interval= 0.879-0.984), 100% sensitivity, and 81.3% specificity. In univariate logistic regression analysis, the presence of bleeding, somnolence, and hypotension at the time of admission; higher troponin, total bilirubin, neutrophil count, activated partial thromboplastin time, prothrombin time, and age; and lower platelet count, fibrinogen, low-density lipoprotein cholesterol, and total cholesterol were significant risk factors determined for poor prognosis. Multivariate logistic analysis performed with these parameters revealed that somnolence, CAR, and BAR were independent risk factors for predicting mortality in CCHF. In conclusion, BAR and CAR, more easily and quickly obtained than severity scores, had higher sensitivity and specificity in predicting mortality than single biomarkers, and can be used during hospital admission for CCHF.