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Open AccessArticle

Characterization of Biomarker Levels in Crimean–Congo Hemorrhagic Fever and Hantavirus Fever with Renal Syndrome

Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
National Institute of Public Health of Kosovo, 10000 Pristina, Kosovo
Author to whom correspondence should be addressed.
Viruses 2019, 11(8), 686;
Received: 14 June 2019 / Revised: 20 July 2019 / Accepted: 25 July 2019 / Published: 26 July 2019
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are important viral hemorrhagic fevers (VHF), especially in the Balkan region. Infections with Dobrava or Puumala orthohantavirus and Crimean-Congo hemorrhagic fever orthonairovirus can vary from a mild, nonspecific febrile illness, to a severe disease with a fatal outcome. The pathogenesis of both diseases is poorly understood, but it has been suggested that a host’s immune mechanism might influence the pathogenesis of the diseases and survival. The aim of our study is to characterize cytokine response in patients with VHF in association with the disease progression and viral load. Forty soluble mediators of the immune response, coagulation, and endothelial dysfunction were measured in acute serum samples in 100 HFRS patients and 70 CCHF patients. HFRS and CCHF patients had significantly increased levels of IL-6, IL-12p70, IP-10, INF-γ, TNF-α, GM-CSF, MCP-3, and MIP-1b in comparison to the control group. Interestingly, HFRS patients had higher concentrations of serum MIP-1α, MIP-1β, which promote activation of macrophages and NK cells. HFRS patients had increased concentrations of IFN-γ and TNF-α, while CCHF patients had significantly higher concentrations of IFN-α and IL-8. In both, CCHF and HFRS patients’ viral load significantly correlated with IP-10. Patients with fatal outcome had significantly elevated concentrations of IL-6, IFN-α2 and MIP-1α, while GRO-α, chemokine related to activation of neutrophils and basophils, was downregulated. Our study provided a comprehensive characterization of biomarkers released in the acute stages of CCHF and HFRS. View Full-Text
Keywords: VHF; CCHF; HFRS; cytokines; biomarkers VHF; CCHF; HFRS; cytokines; biomarkers
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Korva, M.; Resman Rus, K.; Pavletič, M.; Saksida, A.; Knap, N.; Jelovšek, M.; Strašek Smrdel, K.; Jakupi, X.; Humolli, I.; Dedushaj, J.; Petrovec, M.; Avšič-Županc, T. Characterization of Biomarker Levels in Crimean–Congo Hemorrhagic Fever and Hantavirus Fever with Renal Syndrome. Viruses 2019, 11, 686.

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