The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis

<div><p>Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O₂ saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O₂ saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness.</p></div

RSV gene Copy Numbers (CN) are correlated highly and linearly, and correlations improve when data are normalized by RNase P CN.

<p>(A) N CN vs. NS2 CN showing the most correlated pair of CNs measured (r = 0.941; p<0.0001); F CN vs. NS2 CN showing the least correlated pair of CNs measured (r = 0.789; p<0.0001). (B) Normalized N CN vs. normalized NS2 CN (where normalized CN = RSV gene CN/ RNase P CN) showing the most correlated pair of normalized CNs measured (r = 0.963; p<0.0001); normalized F CN vs. normalized NS2 CN showing the least correlated pair of normalized CNs measured (r = 0.808; p<0.0001).</p

Spearman correlations between RNase P-normalized RSV gene copy numbers and biomarker activity levels.

<p>Spearman correlations between RNase P-normalized RSV gene copy numbers and biomarker activity levels.</p

Spearman correlations among the RNase P-normalized copy numbers of 5 RSV genes.

<p>Spearman correlations among the RNase P-normalized copy numbers of 5 RSV genes.</p

RNase P-normalized RSV gene copy numbers between non-hospitalized and hospitalized infants.

<p>RNase P-normalized RSV gene copy numbers between non-hospitalized and hospitalized infants.</p

Demographic and clinical characteristics by disposition.

<p>Demographic and clinical characteristics by disposition.</p

Description of the RNase P-normalized copy numbers of 5 RSV genes.

<p>Description of the RNase P-normalized copy numbers of 5 RSV genes.</p