Cytokine release syndrome in Crimean-Congo hemorrhagic fever: can IL-1 receptor antagonist levels be a guide in its treatment?

Objective: Crimean-Congo Hemorrhagic Fever (CCHF) is a potentially fatal zoonotic viral disease involving fever and hemorrhage. Our aim was to investigate the relationship between interleukin (IL)-1 and IL-1 receptor antagonist (RA) levels in patients with CCHF and the course of the disease and mortality, as well as to contribute to the literature at a time when new therapeutic protocols are being investigated.

Patients And Methods: Sixty-one patients with CCHF were admitted to our hospital's infectious diseases ward between March and September 2022, and 40 healthy people were included in the control group in our study. The patients were divided into mild/moderate (n=35) and severe (n=26) CCHF groups depending on the clinical course. The patients with CCHF were also divided into surviving and exitus groups. IL-1 and IL-1RA levels were measured from blood specimens using the ELISA method.

Results: Significant elevation in IL-1 and IL-1RA levels was observed in CCHF cases with a severe manifestation compared to those with moderate disease. Both patient groups' IL-1 and IL-1RA levels were also significantly higher than those of the control group. In addition, IL-1 and IL-1RA levels were significantly higher among the exitus patients compared to the surviving CCHF patients. The laboratory values of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CK), platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were also significantly higher among the patients with severe manifestations compared to the moderate severity patient group, and in the exitus patients compared to the survivors. However, platelet count and fibrinogen levels were lower in the patients with a severe manifestation compared to the moderate severity group and in the exitus patients compared to the survivors. White blood cells (WBC) were higher in exitus patients than in survivors.

Conclusions: IL-1 and IL-1RA levels were elevated in all the CCHF patients, while the higher values in patients with a fatal course suggest that the inflammatory process is very severe and that IL-1 receptor antagonists may be needed in the treatment.