Role of viral load and host cytokines in determining the disease severity of Respiratory Syncytial Virus associated acute lower respiratory tract infections in children.

Abstract

Respiratory syncytial virus disease (RSV) is an important cause of acute lower respiratory tract infection. This study aimed to evaluate the role of viral load and cytokines, including MMP-9 and TIMP-1, in determining the severity of RSV disease and to identify potential biomarkers of disease severity. 142 patients of RSV (>2 months to <5 years of age) presenting with acute lower respiratory tract infection (ALRTI) between December 2013 to March 2016 were enrolled. Their nasopharyngeal aspirate was subjected to RSV viral load quantification and local cytokine levels of IL-6, TNF, IL-17A, IFN-Ƴ and IL-10 as determined using cytokine bead array. Levels of MMP-9 and TIMP-1 were calculated using Quantikine ELISA on 109 aspirates. These parameters were compared against different categories of disease severity. A higher viral load and increased levels of TNFα, MMP-9 and MMP-9:TIMP-1 were associated with greater severity of disease; while levels of IL-17a, IFN-Ƴ, and IFN-Ƴ:IL-10 were associated with disease resolution. In defining transition from non-severe to severe disease, MMP-9 had a sensitivity and specificity of 89.7% and 85.4%, respectively and MMP-9:TIMP-1 had a sensitivity and specificity of 87.2% and 76.8% respectively. Hence, MMP-9, MMP-9:TIMP-1, TNFα and IL-10 could serve as potential biomarkers for disease progression in RSV-infected children.