Clinical and Immunological Predictors of Hemorrhagic Fever with Renal Syndrome Outcome during the Early Phase.

Geum-Young Lee,Seungchan Cho,Jin Sun No,Hayne Cho Park,Kyungmin Park,Seung-Ho Lee,Won-Keun Kim,Jingyeong Lee,Jongwoo Kim,Jaehun Jung,Jin-Won Song,Yongjin Yi

doi:10.3390/v14030595

Abstract

The ability to accurately predict the early progression of hemorrhagic fever with renal syndrome (HFRS) is crucial for reducing morbidity and mortality rates in severely affected patients. However, the utility of biomarkers for predicting clinical outcomes remains elusive in HFRS. The aims of the current study were to analyze the serum levels of immune function-related proteins and identify novel biomarkers that may help ascertain clinical outcomes of HFRS. Enzyme-linked immunosorbent assay, Luminex, and bioanalyzer assays were used to quantitatively detect 15 biomarkers in 49 serum samples of 26 patients with HFRS. High hemoglobin (HGB) and low urine output (UO) levels were identified as potential biomarkers associated with the acute HFRS. The serum soluble urokinase plasminogen activator receptor (suPAR) and C-X-C motif chemokine ligand 10 (CXCL10) values increased in the early phase of diseases. Elevated suPAR, interleukin-10 (IL-10), CXCL10, and decreased transforming growth factor-beta 3 (TGF-β3) were representative predictors of the disease severity. Upregulation of the HGB showed a significant correlation with high levels of suPAR and CXCL10. Reduced UO positively correlated with increased suPAR, CXCL10, and TGF-β2, and decreased vascular endothelial growth factor and TGF-β3. The changing HGB and UO criteria, high suPAR, IL-10, CXCL10, and low TGF-β3 of HFRS raise significant awareness for physicians regarding prospective biomarkers for monitoring early warning signs of HFRS. This study provides critical insights into the clinical and immunological biomarkers for disease severity and progression in patients with HFRS to identify early predictions of fatal outcomes.

Highlights

Hantaviruses are the causative agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans [1]
The diagnosis of HFRS was made based on a positive enzyme-linked immunosorbent assay (ELISA) for specific IgG and IgM antibodies to Hantaan virus (HTNV) in the serum
77% of enrolled patients were admitted at the intensive care unit (ICU) and were patients with HFRS, and treatment with transfusion, mechanical ventilation, and hemodialysis was required in 12%, 4%, and 4%, respectively

Summary

Introduction

Hantaviruses are the causative agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans [1]. Virus transmission usually occurs through the inhalation of aerosols or dust particles contaminated with virus-containing rodent excreta. Hantavirus infection captured worldwide attention during the Korean conflict from 1950 to 1953, during which more than 3000 United Nations troops fell ill with HFRS [2]. In the early 1980s, the causative agent of the disease was reported to be the Hantaan virus (HTNV) isolated from the lungs of a striped field mouse (Apodemus agrarius), a natural reservoir [3]. The etiologic agent of nephropathia epidemica, a milder form of HFRS, has been reported to be the Puumala virus (PUUV) found in bank voles (Myodes glareolus) in Finland [4]. Pathogenic hantaviruses can cause severe disease in humans, with fatality rates from 1% to 15% [1,5]

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