The post-SARS rush of research on human coronaviruses (CoVs) might not result in an immediate cure for SARS. But if recent publications are any indicator, it may fuel some solid insights into diseases such as the common pneumonias as well as the rare Kawasaki syndrome.

This year started with several papers that identified what may turn out to be at least two novel human coronaviruses that cause serious illness. First, a Hong Kong team that was one of the first to sequence the SARS CoV published findings of a new coronavirus, CoV-HKU1, which was present during the SARS outbreak.[1] The discovery was a serendipitous one, according to the researchers who examined specimens obtained in early 2003 from patients suspected of having SARS.

K.Y. Yuen, who led the Hong Kong team, sees nothing extraordinary about the illness retrospectively diagnosed as CoV-HKU1. Unlike SARS, the virus' pathogenicity does not stand out. "We cannot use clinical symptoms and signs to differentiate it from common community-acquired pneumonia," he says. "We need to do laboratory tests like RT-PCR [real-time PCR]." Yuen says studying the new virus further will be challenging, however, because culturing the HKU1 virus is difficult compared with culturing SARS.

Scientists now say that many more coronaviruses that cause serious disease might be constantly circulating. Yuen's team has "good evidence that they have an agent through molecular methods," says Dean Erdman, a researcher at the US Centers for Disease Control and Prevention (CDC) who was also one of the first scientists to characterize and sequence the SARS virus. However, evidence of the virus in cytopathic assays and direct culture is scant.

Erdman says that HKU1 is most similar to another type 2 human coronavirus, OC43, known to scientists since the 1960s. Erdman didn't think the virus recently jumped from animals as did the SARS CoV, so the pathogen has probably been causing serious pneumonia in humans for decades or longer.

In another recent paper, Jeffrey Kahn and colleagues at Yale University found a link to a different novel coronavirus having some similarities to SARS: the virus that causes Kawasaki syndrome, the leading cause of acquired heart disease in the United States.[2] "We took all the genetic sequences of mammalian human and avian coronaviruses available on GenBank, and we looked for conserved regions [and] for probes from these conserved regions, and we began to screen respiratory specimens," says Kahn.

One of the samples tested positive for the newly named HCoV-NH (New Haven virus). Kahn's team soon discovered that KS had been diagnosed in that patient, so they went on to test more specimens from patients with KS. Eight of the 11 specimens (72%) from children with Kawasaki syndrome tested positive for HCoV-NH, while only one (4.2%) of the 22 control specimens from children without respiratory disease tested positive.

While Kawasaki syndrome has disappointed scientists in the past with a shopping list of seemingly promising causative agents (all of which turned out to be red herrings), CDC scientists, including Erdman, are optimistic about the results. Nonetheless, despite a highly significant correlation, the finding is being received with a fair amount of skepticism. Ian Mackay, who heads a research unit at the Royal Children's Hospital in Queensland, Australia, isn't convinced that HCoV-NH is new. "It seems like it's perhaps a strain of NL63 if anything, rather than a novel virus," he says.

McKay says the New Haven team might have isolated a variant of HCoV-NL63, a coronavirus isolated last year in the Netherlands.[3] Mackay's group recently published evidence that the HCoV-NL63 strain causes serious lower respiratory tract disease in Australia.[4] However, he doesn't rule out the possibility that NL-63 could also cause Kawasaki syndrome.