Human Coronavirus NL63: A Clinically Important Virus?

Abstract and Introduction

Abstract

Respiratory tract infection is a leading cause of morbidity and mortality worldwide, especially among young children. Human coronaviruses (HCoVs) have only recently been shown to cause both lower and upper respiratory tract infections. To date, five coronaviruses (HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63 and HCoV HKU-1) that infect humans have been identified, four of which (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU-1) circulate continuously in the human population. Human coronavirus NL63 (HCoV-NL63) was first isolated from the aspirate from a 7-month-old baby in early 2004. Infection with HCoV-NL63 has since been shown to be a common worldwide occurrence and has been associated with many clinical symptoms and diagnoses, including severe lower respiratory tract infection, croup and bronchiolitis. HCoV-NL63 causes disease in children, the elderly and the immunocompromised, and has been detected in 1.0–9.3% of respiratory tract infections in children. In this article, the current knowledge of human coronavirus HCoV-NL63, with special reference to the clinical features, prevalence and seasonal incidence, and coinfection with other respiratory viruses, will be discussed.

Introduction

Acute respiratory tract infections (ARTIs) are among the most common causes of disease in humans.^[1] The majority of ARTIs are caused by viruses with rhinovirus, respiratory syncytial virus, influenza virus, enterovirus, human metapneumovirus and parainfluenza virus considered the major pathogens.^[1–3] Those most at risk of severe complications from these viral infections include young children, the elderly or persons with compromised cardiac, pulmonary or immune systems.^[2,4] The high burden of disease caused by respiratory viruses in young children has led to the development of diagnostic tests and vaccines for the treatment of these infections.^[5]

Until recently, it was commonly accepted that the known human coronaviruses (HCoVs), with the exception of severe acute respiratory syndrome Cov (SARS-CoV), mainly cause mild upper respiratory tract infections (URTIs).^[6] For this reason, the circulation of HCoVs was not monitored and no attempt to develop vaccines or drugs against these viruses was made.^[7] CoVs are ssRNA viruses that infect humans and animals. In animals, CoVs cause a wide spectrum of diseases, including respiratory, enteric, hepatic and neurological diseases, with symptoms ranging from mild to severe.^[8,9] HCoVs causing URTIs were first isolated from patients in the 1960s,^[8] with HCoV-229E and HCoV-OC43 the best characterized. Then, following the outbreak of SARS in China in 2003, three additional human coronaviruses were identified – SARS-CoV,^[10–12] HCoV-NL63^[13,14] and HCoV-HKU1.^[15] Of the five known HCoVs, four (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) are circulating continuously in the human population.

This article aims to summarize the current knowledge of HCoV-NL63 with reference to the clinical features, prevalence and seasonal incidence, and coinfection with other respiratory viruses. Finally, perspectives for future developments in the field are discussed.

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

Abstract and Introduction

Abstract

Introduction

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References

Authors and Disclosures

Authors and Disclosures

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