Newly Discovered Virus Linked to Childhood Lung Disorders and Kawasaki Disease

A newly discovered virus may be responsible for many respiratory tract illnesses in infants and children, and may be associated with an important multi-organ disease whose cause has remained a mystery for decades, according to articles in the Feb. 15 issue of The Journal of Infectious Diseases, now available online. The virus is one of the numerous coronaviruses, most of which infect animals. In humans, coronaviruses have been known primarily for causing colds or, more recently, severe acute respiratory syndrome (SARS). Genetic evidence now suggests that a previously unknown coronavirus may account for some of the many respiratory diseases for which a causative agent is unidentified, and may have a role in Kawasaki disease, the most common cause of acquired heart disease in children in developed countries.

In the first of two studies, Jeffrey S. Kahn and co-workers at Yale University used molecular probes targeting a gene that is common in human and animal coronaviruses to screen hundreds of specimens for coronavirus genetic material. Ultimately, two specimens were identified in which the sequence of chemical building blocks of the gene differed from that of known human coronaviruses. The Yale investigators, terming the novel virus indicated by their findings the New Haven coronavirus, then used probes specific for the virus to screen respiratory specimens from 895 symptomatic children under age 5 who had tested negative for other viral infections. They found 79 (9 percent) who were positive for the new virus, nine of whom were subsequently found to have evidence of recent infection with another virus as well. Of the remaining 67 patients for whom clinical data were available, signs and symptoms of infection with the new virus included fever, cough, runny nose, rapid breathing, abnormal breath sounds, and hypoxia; 35 had an underlying condition, such as prematurity (19 patients). Indeed, 11 of those infected with the new coronavirus were newborns hospitalized in intensive care.

Analysis of the New Haven coronavirus’s genetic structure showed many similarities to that of a coronavirus recently identified by two groups in the Netherlands, suggesting that the virus may have worldwide distribution.

That Kawasaki disease may be associated with infection by the newly identified New Haven coronavirus was suggested by findings in the Yale group’s second study, which was initiated when they found evidence of the virus’s genetic structure in respiratory secretions from an infant with classic signs of Kawasaki disease. In addition to heart disease, the signs can include conjunctivitis, redness of the mouth or throat, rash, redness or swelling of the hands or feet, and swollen cervical lymph nodes. The investigators then analyzed respiratory secretions from 11 children diagnosed with Kawasaki disease and 22 children without the disease. Eight (73 percent) of the Kawasaki patients but only one (5 percent) of the comparison group tested positive for the New Haven coronavirus.

In an accompanying editorial, Kenneth McIntosh of Harvard University commented that discovery of a new human respiratory coronavirus would not be surprising, since studies in the 1960s and 1970s had pointed to a number of novel coronavirus strains but the findings were not adequately followed up because methods to do so were unavailable at the time. The statistically strong association with Kawasaki disease, however, was “quite surprising.” Noting that previous attempts to link Kawasaki disease to bacteria or other viruses had failed and thus justified healthy skepticism about the present findings, Dr. McIntosh pointed out some “tantalizing facts”: onset of Kawasaki disease is often preceded by a respiratory syndrome; both the disease and respiratory coronavirus infections are seasonal, peaking in the winter and spring; recent studies have described a powerful immune response in the respiratory tract and other organs in acute cases of Kawasaki disease, suggesting the involvement of a specific microbe, which may enter the body through the respiratory tract; finally, as the emergence of SARS illustrates, coronaviruses “are capable of enormously varied pathogenicity.” Despite these encouraging preliminary observations, Dr. McIntosh noted that the association between this novel coronavirus and Kawasaki disease will require confirmation by others in larger future investigations.