Independent and interactive effects of viral species on early-life lower respiratory tract illness

Abstract

Objectives: To determine the association between viral species and odds of severe lower respiratory tract illnesses (sLRI) versus upper respiratory illness (URI) among children under 2 years of age.

Methods: Infants (n=2,061) enrolled in the Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes were surveilled for respiratory illnesses until age 2 years (March 2020 to April 2024). Nasal swabs from 1,363 illnesses (774 participants) were screened for 21 pathogens.

Results: RSV infections occurred in 23% of sLRIs and increased odds of sLRI vs URI (OR=9.28; 95% CI, 5.43-15.85). Metapneumovirus, parainfluenza, and non-SARS-CoV-2 coronavirus also increased odds of sLRIs, while SARS-CoV-2 was associated with lower risk of sLRIs. Rhinovirus (43%) and bocavirus (16.1%) were commonly detected, but were not associated with sLRI risk. Co-infection with multiple viral species was associated with 2.92-fold greater odds of sLRI (95% CI, 2.05-4.16) compared to single viral species infections. Rhinovirus-bocavirus was the most common co-infection, and interaction between these viruses was associated with increased odds of sLRI.

Conclusions: Diverse viral pathogens drive early-life sLRIs. Some (e.g. RSV and metapneumovirus) have intrinsic propensity to cause sLRIs, while other viruses' lower airway pathogenicity depends on other factors, including co-infection.

Keywords: Coinfection; Infants; Pediatrics; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Rhinovirus.