In this study of 110 healthy, community-based infants, RSV was rarely detected (1.8 %). By contrast, rhinovirus was detected in the nasal swab specimens from 14.5 % of healthy infants, with predominance of rhinovirus-A and -C. When limiting our analysis to those who were completely asymptomatic at screening and enrollment, the rhinovirus prevalence decreased to 11.5 %.
Despite the research importance of rhinovirus (overall and species) detection in asymptomatic “healthy” infants, the literature remains sparse [12, 13]. Our rhinovirus findings are in agreement with a prior U.S. study on asymptomatic infants (0–5 months), which found overall rhinovirus prevalence of 11.4 % with a rhinovirus-A and -C predominance (rhinovirus-A 7.0 %, rhinovirus-B 0 %, and rhinovirus-C 4.4 %) [12]. However, the earlier study differed by including children with comorbidities such as wheezing, chronic heart–lung disease, and immunodeficiency. In addition, other community-based studies were conducted among infants at high risk for atopy, including a Dutch study that used nasal brush specimens and found a rhinovirus prevalence of 17 % among 6 month old asymptomatic infants, the majority of whom had a parent with allergic disease [5]. Likewise, in the Childhood Origins of Asthma study, the rhinovirus prevalence was 32 % using nasal washes among infants <1 year, all of whom were at high risk for atopy [5]. Additional studies among healthy, community-based infants age <1 year using nasopharyngeal swabs or nasal washes reported rhinovirus prevalence of 12–24 %, but based on small samples (n < 35 subjects) [7, 8]. A major strength of our study, compared to previous research, is assessing viral prevalence and rhinovirus species in a young population (median age 3.8 months, comparable to the median age of bronchiolitis hospitalization [4]) without comorbidities or high-risk of atopy.
Interestingly, we found that the rhinovirus genomic load among infants with rhinovirus detection was intermediate [14]. The mechanisms of rhinovirus positivity are unclear and likely multifactorial—e.g., active replication without respiratory symptoms, prolonged viral shedding, delayed clearance, and combinations of these factors in the population. The observed difference in patient characteristics (e.g. a higher rate of day care attendance and exposure to passive smoke in home among infants with rhinovirus detection) may paly a role in these potential mechanisms. The significance and mechanisms of rhinovirus detection in asymptomatic children merit further investigation.
Our finding of low RSV prevalence in asymptomatic infants suggests that RSV is likely the causative agent when detected in the setting of clinical symptoms of bronchiolitis. By contrast, given the observed prevalence of rhinovirus in infants without ARI, and even in infants without any respiratory symptoms, it remains unclear if rhinovirus detection always reflects current illness. Rhinovirus is frequently detected in the setting of multiple coexisting viruses [4]. Although a recent study of healthy infants showed that persistence of rhinovirus genome beyond 30 days was uncommon, 8.9 % of distinct rhinovirus infections lasted longer than 14 days, and 4.5 % lasted longer than 30 days [15]. Thus, while rhinovirus detected during bronchiolitis hospitalization can have an etiologic role, an alternate scenario is that the detected rhinovirus is persistent from a previous infection, and perhaps a marker of subject susceptibility or impaired immune response to rhinovirus infection. The generally higher rhinovirus prevalence found in studies of asymptomatic infants at high risk for atopy [5] may support this theory.
Our study has several potential limitations. First, the sample size, although larger than several prior studies, remains relatively small and all infants were recruited from one group practice in Boston, which may limit our generalizability to other settings. Second, this study was a single-year study; therefore, it is possible that an outbreak of a less virulent strain of rhinovirus occurred during this study period. Additionally, specimens were collected from late fall to early spring, yet rhinovirus infections occur year-round. While the observed prevalence could be different in months we did not enroll subjects, this chosen study period is helpful for bronchiolitis researchers. Third, ours study did not test other respiratory viruses, such as adenovirus, coronavirus, and human metapneumovirus. However, RSV and rhinoviruses are the most frequently detected respiratory viruses in young children (e.g., 85 % in children hospitalized for bronchiolitis [4]). Lastly, this cross-sectional study did not follow up the infants after enrollment to determine if some went on to develop ARI in the days after sample collection. Nevertheless, our results add to a surprisingly sparse literature and will aid interpretation of studies on viral bronchiolitis.