Human Coronavirus NL63

Burtram C Fielding


Future Microbiol. 2011;6(2):153-159. 

In This Article

Respiratory Clinical Findings

Scientific and clinical evidence show that HCoV-NL63 infects both the upper and lower respiratory tract,[36] causing symptoms similar to those associated with HCoV-229E and HCoV-OC43. Commonly, patients diagnosed with HCoV-NL63 infections of the upper respiratory tract present with mild symptoms, such as fever, cough, sore throat and rhinitis.[18] It is important to remember though, that the reports of symptoms in young children, who represent the majority of cases, are based mainly on parental observations, which often do not include possible subjective signs and symptoms. In addition, most studies are case reports of patients who have been hospitalized for acute respiratory tract infections (and other milder symptoms are ignored in favor of treating the more severe ones) and studies are often limited by small sample sizes or short periods of assessment.[36] For these reasons the involvement of HCoV-NL63 in many other diseases could be overlooked.

Recent studies have reported an association between HCoV-NL63 infection and more severe LRTIs.[21,30,45] LRTIs are the leading cause of morbidity in children younger than 5 years of age worldwide.[46,47] A recent study by Dominguez and colleagues reports that even though HCoV-NL63 and HCoV-OC43 were equally prevalent during their 1-year study period, HCoV-NL63 was more often associated with more severe LRTIs and subsequent hospitalization.[21] One of the most worrying clinical diagnoses of HCoV-NL63 infection is bronchiolitis, an inflammation of the membranes lining the bronchioles,[22,24,25,30,45,48,49] and although a study of children hospitalized with fever and acute respiratory symptoms in China did not report an association of HCoV-NL63 with bronchiolitis,[19] it still believed to be one of the presenting symptoms.

Several research groups have linked HCoV-NL63 infections to croup.[5,17,19,28,30,43,50–52] Croup children present with pharangitis, sore throat and hoarseness of voice, and infected children are considered for hospitalization. The chance of developing croup is 6.6-times higher in HCoV-NL63-infected children than in HCoV-NL63-negative children.[30] Another study reports that HCoV-NL63, when compared with other respiratory viruses, is the virus second-most commonly associated with young children (median age 13 months) hospitalized with croup.[17] In fact, HCoV-NL63 appears to be more frequently associated with croup than HCoV-229E and HCoV-OC43.[7] Previously, the etiological agent of croup was generally assumed to be one of the more well-known respiratory viruses, such as the parainfluenza viruses, but it is now clear that HCoV-NL63 also plays a major role in this disease.[9]

It is important to remember that since HCoVs (including HCoV-NL63) are also frequently detected in asymptomatic individuals,[44,53,54] the studies that lack of specimens from healthy individuals limit the inference of a disease association. A recent study, however, reported that for all four circulating HCoVs combined, the detection frequency in samples from patients with URTIs and LRTIs exceeds the proportion seen with samples taken from patients with no respiratory symptoms; this provides epidemiological evidence for the role of HCoVs in the etiology of respiratory disease.[55] Furthermore, since it has previously been shown that HCoV can be detected in clinical samples 14 days after illness,[56] the possibility that some of the control patients in the earlier studies may have been shedding HCoV following an earlier symptomatic infection cannot be excluded.


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