Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children

Abstract

Background: The etiological agents responsible for a substantial proportion of respiratory tract diseases have not been identified. We sought to determine whether novel human coronaviruses (HCoVs) are circulating in New Haven, Connecticut, and, if so, whether they are associated with respiratory tract disease in infants and young children.

Methods: We developed a polymerase chain reaction (PCR)-based approach for screening specimens from the respiratory tracts of symptomatic children. PCR probes that target regions of the replicase 1a gene that are conserved among genetically diverse animal CoVs and HCoVs were designed. Using these probes, we identified genomic sequences of a novel HCoV, designated "New Haven coronavirus" (HCoV-NH). Thereafter, we designed specific probes to screen respiratory specimens from children <5 years old for this novel HCoV. Clinical features associated with HCoV-NH infection were identified.

Results: Seventy-nine (8.8%) of 895 children tested positive for HCoV-NH. Cough, rhinorrhea, tachypnea, fever, abnormal breath sounds, and hypoxia were the most common findings associated with HCoV-NH infection. Sequence analysis revealed that HCoV-NH is closely related to a novel HCoV recently reported in The Netherlands.

Conclusions: The novel HCoVs identified in New Haven and The Netherlands are similar and likely represent the same species. This newly discovered virus may have worldwide distribution and may account for a significant proportion of respiratory tract disease in infants and young children.

Figure 1.

Age distribution of New Haven coronavirus (HCoV-NH)-positive children <5 years old. HCoV-NH infection in children hospitalized since birth at the newborn intensive care unit (NICU), Yale-New Haven Hospital (CT), is represented by black bars.

Figure 2.

Weekly distribution of New Haven coronavirus (HCoV-NH)-positive children <5 years old from January 2002 to mid-February 2003. For clarity, only the first day of every other week is labeled. HCoV-NH infection in children hospitalized since birth at the newborn intensive care unit (NICU), Yale-New Haven Hospital (CT), is represented by black bars.

Figure 3.

Phylogenetic analysis of New Haven coronavirus (HCoV-NH). To construct the phylogenetic tree, sequences of a 126-bp portion of the replicase 1a gene of a representative sample of HCoV-NH (NH) amplicons, the HCoV recently identified in The Netherlands (NL-63), HCoV-229E, and transmissible gastroenteritis virus (TGEV) were used.

Table 2.

Respiratory specimens from children <5 years old tested for New Haven coronavirus (HCoV-NH) from January 2002 to mid-February 2003.