Enterovirus D68 seen in cancer, stem cell transplant patients

The virus that sent hundreds of children across the nation to hospital emergency rooms with severe respiratory infections last summer also caused serious illness in adult cancer patients, according to researchers at Fred Hutchinson Cancer Research Center, Seattle Children’s and the University of Washington.

A paper published online Thursday in the journal Blood described the pathogen, enterovirus D68 (EV-D68), in eight adults who had received stem cell transplants or chemotherapy for blood cancers. Two of them required mechanical ventilation and admission to intensive care units.

“We are the first group to describe EV-D68 infections in immunocompromised adults, and we showed that it can cause severe respiratory disease,” said the paper’s lead author, Dr. Alpana Waghmare, a pediatric infectious disease specialist with Seattle Children’s and a Fred Hutch research associate. “The findings of our work have significance not only at our institution, but also to other cancer centers worldwide.”

The researchers noted that in all of the cases in which EV-D68 was identified, there was no evidence that the virus was contracted in the hospital or clinic.

“That speaks to good infection control,” said Dr. Michael Boeckh, head of the Infectious Disease Sciences Program in Fred Hutch’s Vaccine and Infectious Disease Division and a co-author of the paper.  

Preventing, detecting and treating infections are top concerns for cancer centers. Cancer itself as well as cancer treatment can increase a person’s risk of contracting viruses and other pathogens by weakening the immune system, leaving patients vulnerable to respiratory viruses and other pathogens that can lead to pneumonia, respiratory failure and even death. People who receive stem cells from donors may need medicine to keep them from rejecting the stem cells, further suppressing the immune system.

The researchers tested respiratory tract samples collected as part of routine clinical care from adults with symptoms of respiratory infection who were seen at University of Washington hospitals, clinics and the Seattle Cancer Care Alliance between mid-August and early November last year. The samples were tested for 12 other respiratory viruses. Those that tested positive for human rhinovirus, which causes colds and is similar to enterovirus, and those that tested negative to all the viruses in the panel were then tested for enterovirus at the UW Molecular Virology Laboratory, one of the few laboratories in the country that can test for EV-D68. The test was developed for research purposes by UW’s Dr. Jane Kuypers, a Fred Hutch affiliate and also an author on the paper.

Of 506 samples tested, 21 were presumptively positive for EV-D68. Eight of the 21 were patients with a blood cancer. (The remaining patients had underlying conditions including asthma, HIV, heart or blood vessel disease and alcohol abuse.)

The eight blood cancer patients ranged in age from 22 to 69; six had had had stem cell transplants and were on immunosuppressive therapy. Four of the eight patients also had a history of underlying lung disease, which researchers noted was similar to last fall’s outbreak in children, in which many of the confirmed cases involved a history of asthma or wheezing.

Symptoms ranged from mild and manageable in an outpatient clinic to respiratory failure that required admission to intensive care and mechanical ventilation, the study noted. One patient with congestive heart failure and other conditions died, though it was not possible to say what role, if any, EV-D68 played in the death.

The study was not designed to determine how widespread EV-D68 is in cancer patients, but the researchers estimated that it could be the true pathogen in about 10 percent of stem cell transplant patients who test positive for the rhinovirus and up to 5 percent of overall cases in such patients during peak circulation of EV-D68.  The paper noted that current diagnostic test for EV-D68 are limited and cited the need for improved rapid diagnostic tools.

The EV-D68 strain was first identified in the United States in 1962. Until last year’s national outbreak, it had been rare. In children, it typically triggers mild, cold-like symptoms, but can cause severe illness. In 2014, more than 1,000 children were diagnosed with EV-D68 and it was related to 13 deaths, according to U.S. Centers for Disease Control and Protection.

Adults can get infected with enteroviruses, but they are more likely to have no symptoms or mild symptoms. Only one other study has described EV-DG in adults, including solid organ transplant recipients but not cancer patients. 

Around the same time as the outbreak, about 100 children in 34 states came down with an unexplained polio-like illness causing weakness or paralysis of an arm or a leg. Some were infected with EV-D68, but a link to the virus has not been substantiated.

No paralysis was seen in adult patients in the new study, the researchers said.

The virus spreads as easily as a cold, and last year’s outbreak in children occurred in late August and early September, as children returned to school. Adult cancer patients could be vulnerable at that time too.

“What we think is that the kids are the vectors, so as soon as kids start getting it, they pass it on to adults,” said Waghmare. “It’s a little bit of a lag from what we see in kids.”

There are no vaccines or specific treatment for EV-D68 beyond supportive care, including oxygen support or medications that can open airways. At home, people can help protect themselves from getting and spreading EV-D68 and other respiratory illnesses by following basic practices such as washing hands with soap and water for 20 seconds, avoiding touching the face, avoiding close contact with people who are sick, covering coughs and sneezes with a tissue or shirt sleeve and staying home when sick.