Serum Markers Associated with Severity and Outcome of Hantavirus Pulmonary Syndrome

Abstract

BACKGROUND:Hantavirus pulmonary syndrome (HPS) is caused by Andes virus (ANDV) and related hantaviruses in the Americas. Despite a fatality rate of 40%, the pathogenesis of HPS is poorly understood and factors associated with severity, fatality and survival remain elusive.METHODS:Ninety-three ANDV-infected HPS patients, out of whom 34 had a fatal outcome, were retrospectively studied. Serum levels of cytokines and other inflammation-associated markers were analyzed using multiplex immunoassay and ELISA. Associations with disease severity, fatal outcome and survival were identified using logistic regression.RESULTS:HPS patients exhibited increased serum levels of markers associated with inflammation, intestinal damage and microbial translocation compared to controls. Patients with fatal outcome displayed higher levels of IL-6, IL-10, IFN-γ, sTRAIL, and intestinal fatty acid binding protein (I-FABP) than survivors. Levels of complement factor 5/5a were higher in survivors compared to fatal cases. IL-6 and I-FABP, the latter a marker for intestinal damage, were by multivariate analyses identified as independent markers associated with disease severity (odds ratio 2.25 95% CI 1.01-5.01) and fatal outcome (odds ratio 1.64 95% CI 1.01-2.64), respectively.CONCLUSIONS:HPS patients displayed a multifaceted, systemic inflammatory response, with IL-6 and I-FABP as independent markers of disease severity and fatality, respectively.