Human Coronavirus NL63: A Clinically Important Virus?

Nonrespiratory Clinical Findings

To date, one group has reported an association between HCoV-NL63 and Kawasaki disease, a form of early childhood systemic vasculitis that presents as prolonged fever, polymorphic exanthem, oropharyngeal erythema and bilateral conjuctivitis.^[57] In view of this paper, the editorial by McIntosh^[8] made a compelling argument for a possible association between respiratory HCoVs and Kawasaki disease, motivating further study using broader epidemiological and nonepidemiological criteria. All subsequent reports, however, have conclusively demonstrated that no statistical significant link between HCoV-NL63 and Kawasaki disease exists.^[8,58–64]

HCoV-NL63 infections have previously been associated with gastrointestinal findings.^{[21,25,29,65–67]} However, this is not unique to HCoV-NL63 infections, as coronavirus-like particles,^[21] as well as SARS-CoV and HCoV-HKU1 RNA^[68,69] have been previously detected in patient diarrheic samples. These manifestations appear to be a direct consequence of viral invasion of the intestinal mucosa.^[7] In one study, 4 out of 878 stool samples from children with acute gastroenteritis tested positive for HCoV-NL63, and these samples are usually positive for other gastroenteritis viruses as well.^[70] Another study using stool samples collected from 479 patients, reported the absence of HCoV-NL63.^[71] However, this study had several shortcomings, including a short study period, the absence of a control group without gastrointestinal disease, and specimen selection that might be biased towards individuals with more severe disease. Also, the majority of patients included were adults (older than 18 years of age); this is a problem since it has previously been shown that young children are more susceptible to HCoV-NL63 infections. Therefore, the findings of this study cannot exclude the role of HCoV-NL63 in gastrointestinal disease.^[71] Thus far, data show that HCoV-NL63 may, at most, have a minor etiological role in acute gastroenteritis in children, but since other viruses are frequently associated with gastroenteritis in HCoV-NL63 infected individuals, the exact role of HCoV-NL63 is not clear.

Cite this: Human Coronavirus NL63 - Medscape - Feb 01, 2011.

Table 1. Incidence of HCoV-NL63 in clinical samples.
Country	Method used for detection	Incidence (%; sample size)	Ref.
Australia	RT-PCR	3.30 (234)	[31]
Belgium	RT-PCR	2.30 (309)	[29]
Canada	RT-PCR	3.60 (525)	[18]
France	RT-PCR	9.30 (300)	[25]
Germany	Real-time RT-PCR	5.20 (949)	[28,30]
China	RT-PCR	2.60 (587)	[19]
Italy	RT-PCR	1.86 (150)	[27]
Japan	RT-PCR	1.20 (419)	[24]
Japan	RT-PCR	2.50 (118)	[22]
South Korea	RT-PCR	1.60 (515)	[20]
Taiwan	Quantitative RT-PCR	1.30 (539)	[43]
Thailand	RT-PCR	0.42 (1890)	[44]
South Africa	RT-PCR	8.30 (238)	[26]
Switzerland	RT-PCR	7.00 (82)	[23]
Sweden	RT-PCR	6.00 (212)	[32]
USA	RT-PCR	2.20 (1683)	[21]
South Korea	Multiplex RT-PCR	16.5 (182)	[17]
Germany	Real-time RT-PCR	3.90 (1756)	[5]
Norway	Multiplex real-time PCR	4.50 (536)	[33]

RT-PCR: Reverse transcription PCR.
Modified from [74].

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Executive Summary

Prevalence & seasonal incidence

Human coronavirus (HCoV)-NL63 has a worldwide distribution.
HCoV-NL63 infections peak in winter and have an interepidemic period of 2 years.

Respiratory clinical findings

HCoV-NL63 infects both the upper and lower respiratory tracts.
Infection with HCoV-NL63 is often associated with more severe lower respiratory tract infections and subsequent hospitalization.
Lower respiratory tract symptoms include croup and bronchiolitis.

Nonrespiratory clinical findings

The majority of studies did not find an association between HCoV-NL63 infection and Kawasaki disease.
HCoV-NL63 has been detected in a small number of diarrhea stool samples.

Coinfections with other respiratory viruses

Coinfections with other well known respiratory viruses are very common.
HCoV-NL63 viral load is higher in patients infected with HCoV-NL63 alone.
Patients with coinfections are more likely to be hospitalized.

Future perspective

More comprehensive population-based studies are needed to determine the involvement of HCoV-NL63 in the infection of systems other than the respiratory tract.
The development of the HCoV-NL63 infectious clone will greatly aid in understanding this virus.
An animal model is required for virus study and vaccine development.

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Human Coronavirus NL63

Nonrespiratory Clinical Findings

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