Emerging Asian viruses get a lot of attention, be they severe acute respiratory syndrome or fresh flu strains. But new, or at least newly discovered, viruses can be found in far less exotic locales. New Haven, Conn., for example.

That's where Jeffrey Kahn and his colleagues from the Yale University School of Medicine discovered a new coronavirus, which they described in the Feb. 15, 2005, issue of the Journal of Infectious Diseases, now available online. In a separate article in the same issue, they also presented epidemiological evidence that the coronavirus is found in three-quarters of children diagnosed with Kawasaki disease.

Both papers are epidemiological studies, and before they lead to novel therapy approaches, they need to be epidemiologically confirmed. But Kahn, who is an assistant professor of pediatrics and epidemiology at Yale and senior author of both papers, called the findings "another example of the fact that there are a lot of disease-causing viruses out there that we haven't identified yet."

In their first paper, the group used a PCR-based screen to probe about 600 lung mucus samples from children that had symptoms of respiratory disease but tested negative for major childhood respiratory viruses. They were looking for gene sequences that were similar to known sequences of the gene for replicase 1, a conserved gene among human coronaviruses that is necessary for their replication. Using that screening, the scientists identified a coronavirus that had not been previously described in the literature, though it is very similar to a coronavirus that recently was identified in a study in the Netherlands. When the scientists tested about 1,250 samples from nearly 900 children for the presence of New Haven coronavirus, just less than 9 percent tested positive. Eleven of the children that tested positive had been hospitalized in the neonatal ICU since birth, including a 1-day-old child, meaning that the virus was either acquired in the hospital or was infected prenatally.

Virus Potential Cause For Kawasaki, Though Not First

The symptoms associated with New Haven coronavirus infection were by and large fairly unremarkable for a respiratory virus: Cough, runny nose, shallow breath, fever, abnormal breath sounds and hypoxia were the most common findings. However, the scientists were intrigued by the fact that one of the positive samples in their first study came from a patient with Kawasaki disease.

Kahn and his colleagues did a second study, testing the secretions of Kawasaki patients and matched controls for the presence of New Haven coronavirus. Seventy-three percent (eight of 11) of the Kawasaki patients tested positive for New Haven coronavirus, while only 5 percent (one) of the controls had been infected.

While Kawasaki disease itself usually is brief and fairly benign, it leads to heart disease in about 20 percent of the children who contract it, making it the leading cause of acquired pediatric heart disease in the developed world. The cause of Kawasaki disease is unknown, and a diagnosis of Kawasaki disease is based solely on a set of clinical symptoms. In its information on Kawasaki disease, the Centers for Disease Control and Prevention notes that in several outbreaks, "children with [Kawasaki syndrome - KS] had a higher incidence of an antecedent, primarily respiratory, illness (during the 30 days before onset of KS) than did controls matched for age, sex and race. Neither serologic nor isolation studies incriminated a single etiologic agent for this antecedent illness."

While the association between New Haven coronavirus and Kawasaki disease certainly is noteworthy, the findings do not establish a cause-and-effect relationship. Kahn told BioWorld Today that "the findings are purely epidemiological," and would need to be confirmed with larger samples as well as prospective studies before either a causative relationship could be established, or new therapeutic strategies based on those findings.

An accompanying editorial by Kenneth McIntosh, of Harvard Medical School, noted that "the linking of an agent to Kawasaki disease follows a long trail of previously failed or still-struggling attempts to identify the etiologic agent of this important syndrome, ranging from an unidentified retrovirus, to parvovirus B19, to Epstein-Barr virus, to Chlamydia pneumoniae, and to toxin-producing Staphylococcus aureus or Streptococcus pyogenes, with a scattering of others along the way."

But McIntosh (who, with charming honesty, editorialized that for 35 years after the initial description of coronaviruses, research on them was "pretty dull") also noted that "some tantalizing facts about both CoVs and Kawasaki disease" - namely, the previous epidemiological studies showing that Kawasaki disease is preceded by a respiratory infection, the fact that Kawasaki disease and coronaviruses peak during the same season, and recent other reports on immunological precursors to Kawasaki disease - are cause for "cautious optimism" about the association.

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