Study suggests 2014's enterovirus D68 was not more severe than other cold bugs

TORONTO -- The respiratory bug known as enterovirus D68, which caused clusters of children in Canada and the U.S. to get sick in late summer-early fall last year, does not seem to have increased the need for ICU care or the risk of death compared to other cold-causing viruses, a Canadian study suggests.

That's the conclusion drawn from a study of 87 children treated at McMaster Children's Hospital in Hamilton, who tested positive for EV-D68, and 87 other kids who had a different virus causing their cold symptoms.

There are more than 100 enteroviruses, the second most common cause of the common cold after rhinoviruses. EV-D68 tends to cause symptoms in the lower part of the respiratory system, putting children with asthma or wheezing at greater risk of developing more acute illness from the infection; most cold viruses typically affect the upper airways.

The study found that children who turned out to be infected with EV-D68 were more likely to be in respiratory distress when they were seen in the emergency department and more often required hospital admission, compared to kids infected with other enterovirus or rhinovirus strains.

"However, they were not significantly more likely to require admission to the pediatric critical care unit or to die," said lead researcher Dr. Dominik Mertz, medical director of infection prevention and control at Hamilton Health Sciences.

"We didn't find any evidence that they were worse off than children infected by the other strains of the common cold," Mertz said Tuesday from Hamilton.

The study, published Tuesday in the Canadian Medical Association Journal, found 23 per cent of children infected with EV-D68 needed to be cared for in intensive care, with or without a ventilator to assist their breathing. For kids with a different cold virus, 15 per cent needed ICU admission.

That difference, the researchers concluded, is not what's called in medicine "statistically significant."

"So even those with the normal strains, one in seven kids ended up in the ICU," he said. "And I think that's something some people underestimate, the fact that with what is perceived as the common cold, some children can get severely sick from that as well and it doesn't need to be EV-D68."

Dr. Danuta Skowronski, an infectious disease specialist at the B.C. Centre for Disease Control who was not involved in the study, said "it's important and interesting to see the Canadian experience with the enterovirus D68 event last season."

But Skowronski questioned the researchers' conclusion that EV-D68 was not associated with greater risks of admission to a critical care unit or death, suggesting that the number of patients in the study may not have been large enough for such an assertion.

"For me, the risk of further severity -- in other words, admission to ICU or death -- is really an issue of sample size and needs to be resolved," she said from Vancouver.

After examining the data presented in the paper, Skowronski said she would have been more cautious about drawing a similar conclusion "on the basis of these results."

"But I still think their paper is a welcome addition to the body of knowledge around D68 and other enteroviruses generally. And I think enterovirus D68 last year opened our eyes to the severe end of the clinical spectrum."

The EV-D68 outbreak was also associated with neurological symptoms in some children, including a condition called acute flaccid paralysis (AFP), which is characterized by extreme muscle weakness. The enterovirus family -- which includes polio -- is known to be linked with such neurological complications as AFP, meningitis and encephalitis.

But during the 2014 outbreak, not all children who developed AFP tested positive for EV-D68, suggesting that another enterovirus may have contributed to the development of paralysis symptoms in children, suggests an accompanying CMAJ editorial.

"Further studies are needed to define whether EV-D68 is truly a more severe pathogen than other enteroviruses and rhinoviruses for all patients, or whether there are certain populations at increased risk of severe disease," write Drs. Michelle Science and Upton Allen of the Hospital for Sick Children in Toronto.

"Such research should also address whether there are factors that are related to viral or patient genetic variation that might be associated with disease severity."

Skowronski added that future research needs to look at both hospital-based and community-based patients to determine the overall prevalence of EV-D68 "to better reflect the full spectrum of illness."

"Hospital-based clusters are important signals, but we shouldn't hang our hats on them in terms of risk assessment. For that we need much broader community sampling."