The Pediatric Burden of Human Coronaviruses Evaluated for Twenty Years

Abstract
Background: The epidemiology of human coronaviruses (HCoVs) has not been established using reverse transcription polymerase chain reaction techniques in a specimen collection that spans decades. Methods: We used real-time RT-PCR for 3 HCoVs, HCoV 229E, OC43, and NL63, to test nasal wash specimens that had been obtained from a cohort of children <5 years of age with upper or lower respiratory infection (URI, LRI) who were comprehensively followed during the period from 1977 to 2001. Prospectively collected clinical data and archival samples were analyzed. Results: HCoV was detected in 92/1854 (5.0%) of available samples with no known viral etiology of which 9% were 229E, 59% OC43, and 33% NL63. This represented 10/119 (8.4%) of LRI samples and 82/1735 (4.7%) of URI samples. HCoV was not detected every year, but occurred episodically. The recently described HCoV-NL63 was detected as early as 1981. HCoV was associated with 11.4 LRI episodes/1000 child-years <5 years of age (all in children <2 years of age) and 67.3 URI episodes/1000 child-years <5 years of age. Conclusions: HCoV-NL63 and OC43 are associated with a significant proportion of LRI in children less than 2 years of age and a substantial number of medically attended URI episodes.