Low peripheral blood chemokine (C-C motif) ligand 5 and tumor necrosis factor α gene expression is associated with unfavorable progression of respiratory syncytial virus bronchiolitis in infants

Abstract

Objectives: We aimed to analyze whether the expression of inflammatory and antiviral genes in respiratory syncytial virus (RSV)-infected infants' peripheral blood is associated with bronchiolitis progression.

Methods: We conducted a prospective study on 117 infants between 2015 and 2023. The expression levels of nine genes were quantified by quantitative polymerase chain reaction. Infants were classified according to their clinical evolution during hospital admission: (i) non-progression (n = 74), when the RSV bronchiolitis severity remained stable or improved; (ii) unfavorable progression (n = 43), when the RSV bronchiolitis severity increased. The association analysis was performed by logistic regression, adjusted by age, gender, prematurity, and RSV bronchiolitis severity in the emergency room.

Results: Infants were 57.3% male, and the median age of the study population was 61 days. Thirty-five infants (30.7%) were admitted to the intensive care unit after hospital admission. Univariate logistic models showed that tumor necrosis factor (TNFα) and chemokine (C-C motif) ligand (CCL5) gene expression at baseline were inversely associated with unfavorable progression, which was confirmed by multivariate analyses: TNFα (adjusted odds ratio = 0.8 [95% confidence interval = 0.64-0.99], P-value = 0.038) and CCL5 (adjusted odds ratio = 0.76 [95% confidence interval = 0.62-0.93], P-value = 0.007).

Conclusions: An inadequate immune response to RSV, characterized by reduced gene expression levels of CCL5 and TNFα in peripheral blood, was associated with an unfavorable progression of RSV bronchiolitis.

Keywords: Bronchiolitis; CCL5; Gene expression; Peripheral blood; Respiratory syncytial virus; TNFα.