Abstract
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.
Highlights
Viral hemorrhagic fevers (VHF) are an etiologically diverse group of zoonoses with common pathophysiology
Two important causative agents of VHF are present in the Balkan area: Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) and orthohantavirus Dobrava (DOBV) and Puumala (PUUV)
We enrolled 170 patients with CCHF or Hemorrhagic fever with renal syndrome (HFRS) and measured the levels of cytokines and chemokines associated with innate, adaptive Th1, Th2 responses, regulatory T immune response and those involved in endothelial dysfunction and coagulopathy as the major clinical signs of the VHF
Summary
Viral hemorrhagic fevers (VHF) are an etiologically diverse group of zoonoses with common pathophysiology. Clinical manifestations of infections vary from asymptomatic or nonspecific febrile illness that can progress to hypovolemic shock and multi-organ failure and death. Two important causative agents of VHF are present in the Balkan area: Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) and orthohantavirus Dobrava (DOBV) and Puumala (PUUV). Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease with reported a fatality rate of up to 30%. Cases of CCHF are reported in Kosovo, Eastern Europe, Africa, Asia, and the Middle East [1,2,3,4]. The causative agent, CCHFV, is a negative-stranded RNA virus that belongs to the Nairoviridae family of the order Bunyavirales. The virus is transmitted through bites of infected
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