Illness plaguing NY kids eerily similar to Kawasaki disease linked to another coronavirus 15 years ago
New York is currently grappling with a mysterious illness in children potentially related to Covid-19, with symptoms similar to Kawasaki disease and toxic shock syndrome. This is, however, not the first time that a coronavirus has been linked to Kawasaki disease.
In 2005, researchers said that a newly discovered coronavirus may be responsible for many respiratory tract illnesses in infants and children in New Haven, US, and may be associated with an important multi-organ disease whose cause had remained a mystery for decades. The same virus was detected in children with Kawasaki disease.
Genetic evidence suggested that the previously unknown coronavirus may account for some of the many respiratory diseases and may have a role in Kawasaki disease, said researchers. Researchers from Yale University isolated the novel coronavirus called New Haven coronavirus or HCoV-NH from eight children with Kawasaki disease.
Kawasaki disease, which usually affects children 5 years and younger, is the presence of a high fever, rash on back, chest, and abdomen, swollen red hands and feet, and bloodshot eyes, among others.
What is the situation in New York?
On May 9, New York State Governor Andrew Cuomo said during a briefing that hospitals have reported 73 cases of what they now think could be a Covid-19 related illness in children -- mostly toddler to elementary school age -- with symptoms similar to Kawasaki disease and toxic shock syndrome. These children do not present symptoms that one normally associates with Covid-19; it is not a respiratory illness nor are they in respiratory distress. Cuomo also said that three children have died in New York of inflammatory complications possibly linked to Covid-19.
“As it turns out, these children happen to have the Covid-19 antibodies or be positive for Covid-19. But those were not the symptoms they showed when they came into the hospital system. It is a serious situation,” Cuomo said on Saturday.
What did the researchers find in 2005?
Researchers from Yale University obtained specimens from the respiratory tracts of 895 children in the New Haven area who were less than 5 years old and who tested negative for common respiratory infections. In the process, the investigators identified genomic sequences of a novel human coronavirus (HCoV), which they referred to as New Haven coronavirus (HCoV-NH).
“They 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,” says the 2005 study published in The Journal of Infectious Diseases.
The team found 79 (9%) 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). 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 identified in 2004 by two groups in the Netherlands, suggesting that the virus may have a 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 a 6-month-old infant with classic signs of Kawasaki disease. The investigators analyzed respiratory secretions from 11 children diagnosed with Kawasaki disease and 22 children without the disease. Eight (72.7%) of the Kawasaki patients tested positive for the New Haven coronavirus, compared with only one (4.5%) child out of 22 in the comparison group.
“We identified evidence of a novel human coronavirus, designated “New Haven coronavirus” in respiratory secretions from a 6-month-old infant with classic Kawasaki disease. To further investigate the possible association between HCoV-NH infection and Kawasaki disease, we conducted a case-control study,” says the team. “Specimens of respiratory secretions from 8 of 11 children with Kawasaki disease and from 1 of 22 control subjects (children without Kawasaki disease matched by age and the time the specimens were obtained) tested positive for HCoV-NH. These data suggest that HCoV-NH infection is associated with Kawasaki disease,” they add.
The research team also said that if HCoV-NH infection is the cause of Kawasaki disease and is common, it was unclear why the disease occurs in a relatively small number of children. “Further studies -- such as prospective cohort studies, seroepidemiological investigations, and investigations of inflamed tissue for the presence of virus -- are required to determine the precise role played by HCoV-NH in the pathogenesis of Kawasaki disease and to determine whether other infectious agents can also trigger this syndrome,” the experts recommended.
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 several 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.”
Despite the encouraging preliminary observations, Dr McIntosh had said that the association between this novel coronavirus and Kawasaki disease would require confirmation by others in larger future investigations.
According to experts from Murdoch Children's Research Institute, and the University of Sydney, while it may be tempting to conclude that Covid-19 may trigger Kawasaki disease, one should be cautious. The findings of the 2005 study could not be replicated in other groups of children with Kawasaki disease, they say.
“There are as yet few details on the cases and not all children had positive tests for SARS-CoV-2 – nor all the features of Kawasaki shock syndrome. Many children are also older than is typical of Kawasaki disease. Further, both Kawasaki disease and COVID-19 cause illness via excessive inflammation, particularly of blood vessels. And both diseases can progress to a state of overwhelming whole-body inflammation sometimes called a cytokine storm. So it might be difficult to differentiate one disease from the other in their most severe forms,” they write in The Conversation.
The experts say that another possible explanation could be that Covid-19 led to bacterial infection, which then caused features similar to those of Kawasaki disease or toxic shock syndrome.