Coronavirus NL63 Illnesses in Infancy are a Risk Factor for Asthma at Age Six

Abstract

RATIONALE: In infancy, rhinovirus illnesses and severe RSV bronchiolitis indicate increased risk for recurrent wheezing and asthma, but there is less information about other viruses. We evaluated the frequency and severity of metapneumovirus (HMPV) and coronavirus (HCV) infections in a high-risk group of infants. METHODS: Nasal lavage samples were obtained in the first year of life during scheduled study visits and symptomatic respiratory illnesses as part of the Childhood Origins of Asthma Project (COAST). Samples (n 5 567) were analyzed by Respiratory Multicode Assay (RMA) for HMPV, HCV-229E, HCV-OC43, HCV-NL63 and HCV-SARS. RESULTS: HMPV was isolated in 10.7% of samples during illnesses (n 5 291), and also occurred with other respiratory viruses (4.8%). 47.8% of HMPV illnesses included wheezing. HCV were isolated in 19.2% of the samples during illnesses and included HCV-OC43 (10.0%) and HCV-NL63 (9.6%). In addition, HCV was commonly detected together with other respiratory viruses (6.5%). Of all HCV illnesses (n 5 42), 33.3% included wheezing; however, HCV-NL63 had a significantly higher wheezing rate compared to HCV-OC43 (37.5% vs. 4.5%, p 5 0.028). Children who had at least one HCV-NL63 illness during infancy were significantly more likely to have asthma at age 6 compared to those without HCV-NL63 illnesses (52.2% vs. 25.0%, p 5 0.007). Having either HCV-OC43 or HMPV was not a risk factor for asthma at age 6. CONCLUSIONS: Improvements in viral diagnostics has allowed for identification of viruses that are difficult to culture. In infancy, HCV-NL63, HCV-OC43 and HMPV were significant causes of wheezing illnesses, however, only HCV-NL63 was significantly associated with asthma development at age six.

The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children

“…The results of the COAST Study 7,8,12 and the subsequent study from Australia 9 appear to be in contrast to our initial findings that the administration of palivizumab in infancy protects premature subjects against subsequent recurrent wheezing in the first 3 to 4 years of life. 6 This prompted us to examine the potential for a differential effect of RSV prevention in those with and without an atopic diathesis.…”

“…A Spanish study showed that human metapneumovirus and RSV in infancy were associated with asthma at age 5 years, 11 and the COAST Study showed that human coronavirus NL63 but not human metapneumovirus produced asthma at age 6 years. 12 Thus, the relationship between early RSV LRTI and allergic sensitization in the development of asthma at a later age is still unresolved. This controversy prompted us to examine the effect of the family history of atopy on the prevention of later recurrent wheezing in premature infants who had received palivizumab in the first year of life compared to controls.…”

RSV hospitalisation and healthcare utilisation in moderately prematurely born infants

“…There have been studies suggesting that other viruses may be important in the development of subsequent wheezing/asthma in infants born at term. In the COAST study, rhinovirus was the most important association of development of wheezing at 3 [14] and 6 [10] years in children with a strong family history of atopy, and in another study [18], human coronavirus NL63 was associated with asthma at 6 years. Other studies have suggested that other viruses in combination with RSV may increase subsequent morbidity.…”