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. 2005 Jun 15;40(12):1721-9.
doi: 10.1086/430301. Epub 2005 May 10.

Human coronavirus NL63 infection and other coronavirus infections in children hospitalized with acute respiratory disease in Hong Kong, China

Susan S Chiu  1 , Kwok Hung Chan, Ka Wing Chu, See Wai Kwan, Yi Guan, Leo Lit Man Poon, J S M Peiris
Affiliations

Human coronavirus NL63 infection and other coronavirus infections in children hospitalized with acute respiratory disease in Hong Kong, China

Susan S Chiu et al. Clin Infect Dis. .

Abstract

Background: Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43).

Methods: We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002.

Results: Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (+/- standard deviation [SD]) of the infected children was 30.7 +/- 19.8 months (range, 6-57 months). The mean maximum temperature (+/- SD) for the 12 children who were febrile was 39.3 degrees C +/- 0.9 degrees C, and the mean total duration of fever (+/- SD) for all children was 2.6 +/- 1.2 days (range, 1-5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season.

Conclusions: HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged < or = 6 years each year in Hong Kong.

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Figures

Table 1
Table 1
Viruses identified in nasopharyngeal aspirate specimens obtained from 587 hospitalized children.
Table 2
Table 2
Comparative results of RT-PCR using consensus and specific primers for human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E) in nasopharyngeal aspirate specimens of 587 hospitalized children.
Figure 1
Figure 1
A, Seasonality of human coronavirus infections in Hong Kong, China. The percentage of subjects with RT-PCR positive for human coronavirus NL63 (HCoV-NL63), OC-43 (HCoV-OC43), and 229E (HCoV-229E), as well as human metapneumovirus (hMPV), in the study population of 587 patients is shown.B, The percentage of patients positive for influenza virus A or B, parainfluenza virus (Para), adenovirus, and respiratory syncytial virus (RSV) among all 2684 pediatric admissions during this same period. Adapted from [4].
Table 3
Table 3
Clinical data on children with human coronavirus NL63 RNA detected in nasopharyngeal aspirate (NPA) specimens.
Table 4
Table 4
Comparison of clinical manifestations for 11 children infected solely with human coronavirus NL63 (HCoV-NL63), influenza virus A, or respiratory syncytial virus (RSV).
Figure 2
Figure 2
Correlation of human coronavirus NL63 (HCoV-NL63) load and duration of illness. Patients with multiple respiratory pathogens are excluded from this analysis. Viral load is expressed as genome copies per reaction, and 1 genome copy per reaction approximates to 326 copies per 1 mL of nasopharyngeal aspirate (NPA) material. The viral load appears to correlate inversely with time after onset of clinical symptoms, withr = -0.8 (by Pearson Correlation coefficient). The equation log10 (viral load) = -1.09 (day) + 4.96 was found to predict HCoV-NL63 load in the NPA specimen in relation to symptom onset.
Figure 3
Figure 3
Phylogenetic analysis of the human coronavirus NL93 (HCoV-NL63) polymerase 1a gene region. Phylogenetic trees were constructed by the neighbor-joining method, and bootstrap values were determined by 1000 replicates in MEGA 2.1 (available at http://www.megasoftware.net). Viral sequences generated from this study are in bold. Two complete viral genome sequences, HCoV-NL63 and human group 1 coronavirus associated with pneumonia (human group 1 coronavirus), and other reference sequences were obtained in GenBank (accession numbers AY518894, AY567488-AY567494, NC 005831, and AY675541–675553). Genetic sequences from 4 other patients could not be obtained, because the primers for the polymerase 1a region did not amplify a PCR product of sufficient quantity to allow reliable genetic sequencing analysis.
Table 5
Table 5
Characteristics of children with human coronavirus OC43 infection.
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