A Hypothesis-Generating Prospective Longitudinal Study to Assess the Relative Contribution of Common Respiratory Viruses to Severe Lower Respiratory Infections in Young Children

Abstract

Background: Respiratory viruses such as respiratory syncytial virus (RSV), influenza, parainfluenza and human metapneumovirus are wellestablished etiologies of acute lower respiratory tract infections (ALRIs; LRI-viruses). In contrast, adenovirus (AdV), rhinovirus/enterovirus (RV/ EV) and seasonal human coronaviruses (CoV), collectively termed AdV/ RV/CoV, are detected both in healthy children and children with ALRI. Methods: The methods include a prospective longitudinal case-control study, assessing the prevalence of LRI-viruses versus AdV/RV/CoV in ALRI [community-acquired alveolar pneumonia (CAAP) and bronchiolitis] during hospitalization (visit 1), 7-14 days (visit 2) and 28-35 days (visit 3) in 2-17-month-old children. Controls were 2-27-month-old children hospitalized for elective surgery during the same respiratory seasons. Results: We enrolled 99 infants (37 CAAP, 38 bronchiolitis and 24 controls) and obtained 211 nasopharyngeal swabs. Overall, 163 (77%) had greater than or equal to 1 viruses detected; RV/EV (n = 94; 45%) and RSV (n = 71; 34%) were the most frequently detected viruses. In CAAP, the overall LRI-virus prevalence was 78.4%, 32.4% and 5.4% in visits 1, 2 and 3, respectively; the respective rates in bronchiolitis were 73.7%, 34.5% and 8.0%. In controls, no LRI-viruses were detected. In contrast, the overall AdV/RV/CoV prevalence was high among controls (70.8%) and similar among CAAP (48.6%, 40.5% and 40.5%) and bronchiolitis (47.4, 58.6% and 64.0%) across visits.Conclusions: Among ALRI cases, LRI-viruses dominated during the acute disease, with prevalence declining within 28-35 days, suggesting their causative role. In contrast, AdV/RV/CoV prevalence was similar during all 3 visits and in controls, suggesting that carriage of these viruses is common during the viral respiratory season. The current study is relatively small and of short duration; however, the findings are supported by other recent studies.

Use of Rapid Antigen Triple Test Nasal Swabs (COVID-VIRO ALL-IN TRIPLEX: Severe Acute Respiratory Syndrome Coronavirus 2, Respiratory Syncytial Virus, and Influenza) in Children With Respiratory Symptoms: A Real-life Prospective Study

“…Although human metapneumovirus (HMPV) is also detected more frequently in children with respiratory infections, other viruses such as adenovirus or rhinovirus are detected in both healthy children and in children with respiratory infections [ 27 ]. In ambulatory settings, data regarding the circulation of HMPV are scarce [ 28 ].…”

“…In ambulatory settings, data regarding the circulation of HMPV are scarce [ 28 ]. Although the triple test targets the main respiratory viruses such as SARS-CoV-2, RSV, and influenza (well-established etiologies of respiratory infections), HMPV is not yet included in this test [ 27 , 29 ]. The addition of an HMPV antigen test in the current triple test could be relevant.…”

Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment in Germany

“…However, clinical and laboratory findings should also be considered. Detecting a respiratory virus does not exclude the possibility of a bacterial (co-)infection [ 56 , 57 ]. If a bacterial LRTI is likely, ABT adjustment for relevant microbial findings from the respiratory specimen should be made at this time.…”

The Respiratory Microbiome in Paediatric Chronic Wet Cough: What Is Known and Future Directions

“…While metagenomic studies of adult bronchiectasis are emerging [ 23 ], we are unaware of any paediatric studies to date. As a result, current understanding of the respiratory virome among children with PBB or bronchiectasis is based only on PCR data [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

“…Notably, virus-positive children were more likely to require hospitalisation [ 40 ]. Despite the high HRV prevalence in the paediatric PBB and bronchiectasis populations, observed associations with disease may be confounded by the virus’ high prevalence in both symptomatic and asymptomatic childhood respiratory infections [ 5 , 39 , 43 , 52 ]. Thus, cautious consideration of HRV associations with disease is needed, particularly where testing is performed using upper respiratory specimens.…”