Epidemiology and Clinical Presentations of the Four Human Coronaviruses 229E, HKU1, NL63, and OC43 Detected over 3 Years Using a Novel Multiplex Real-Time PCR Method

Abstract

Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.Four human coronaviruses (human coronavirus 229E [HCoV-229E], HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory symptoms, including highmorbidity outcomes such as pneumonia and bronchiolitis (26,31,35). Specifically, HCoV-NL63 has been associated with croup (33) and HCoV-HKU1 with febrile convulsion (18). Coronaviruses are frequently codetected with other respiratory viruses, particularly with human respiratory syncytial virus (HRSV) (17). Whether coronaviruses contribute to disease severity in such coinfections is currently unclear. Other coronaviruses infecting humans include human enteric coronavirus, which is closely related to HCoV-OC43 and is associated with necrotizing enterocolitis and gastroenteritis (10,27).Coronaviruses are globally distributed (7,32,34,38), although there are differences in the frequency of detection of the four viruses in different parts of the world at different times (6,11,15,16,22,28,29). Longitudinal studies of coronavirus epidemiology are lacking in the literature and are restricted to descriptions representing a maximum of 1 year for all four respiratory coronaviruses or 2 years for three coronaviruses (9,17,18). Th...

Primeira detecção de coronavírus humano associado à infecção respiratória aguda na Região Norte do Brasil

“…Entretanto, alguns estudos têm mostrado uma maior frequência da infecção pelo vírus entre os meses de dezembro e abril 8 . Não existem, também, estudos que comprovem a discrepância de susceptibilidade à infecção entre faixas etárias.…”

Infections with human coronaviruses NL63 and OC43 among hospitalised and outpatient individuals in São Paulo, Brazil

“…The incidence and clinical features of HCoV infections in Brazilian patients with respiratory illness is not well known, especially among adults. There are few studies that describe HCoV infections among adults (Bellei et al 2008, Gaunt et al 2010. The aim of the present study was to investigate the occurrence of HCoVs among Brazilian outpatients and hospitalised patients who received care at the Hospital of São Paulo Federal University, Brazil, during 2009 and 2010.…”

“…The composition of our subject pool could be a limitation of our study and might explain the small number of coronavirus-positive cases. Gaunt et al (2010) detected 0.3-0.85% coronavirus-positive samples across all ages and we hypothesised that the H1N1 2009 influenza pandemic wave might have influenced the dynamics of the other respiratory viruses, mainly in 2009. The coronavirus-positive rate found among adults revealed that HCoVs may be representative causal agents of respiratory disease among adults as well as children.…”

Coronavirus Infections in Pediatric Outpatients with Febrile Respiratory Tract Infections in Hiroshima, Japan, over a 3-Year Period

“…HCoV was present in only 15 (3.0z) of 495 febrile pediatric outpatients with RTI. Several other studies, each conducted over a period 1 year, in various clinical settings, have found detection rates of 2.1z to 7.6z for these four HCoV strains (4,5,(15)(16)(17)(18). In the present study, the rate of HCoV infection was markedly lower than those for each of 8 other common respiratory viruses, but not lower than that of Flu-C. Of 4 other studies that used PCR to examine the incidence of common respiratory viruses (RSV, PIV1-3, AdV, and HMPV) and HCoVs (4,5,15,16), 3 found that the rates of HCoV detection were the lowest among the respiratory viruses tested (4,15,16).…”

“…Two of the HCoV strains (HCoV-OC43 and HCoV-229E) were detected predominantly in individuals with common colds (3)(4)(5)(6). Thereafter, three new HCoV strains were identified via molecular and tissue culture assays: severe acute respiratory syndrome coronavirus (SARS-CoV) (7), coronavirus strain noted in The Netherlands (HCoV-NL63) (8,9), and coronavirus strain noted in Hong Kong (HCoV-HKU1) (10).…”