Reports of more than a dozen cases of dangerous and often deadly viral sepsis in babies in Europe — along with increasing circulation of similar viruses that typically spike in the summer and early fall — have pediatric infectious diseases experts in the U.S. on edge.
“We are all on pins and needles here in the States,” said Dr. David Kimberlin, a co-director of the division of pediatric infectious diseases at the University of Alabama at Birmingham.
Enteroviruses can severely affect newborns, whose immune systems aren’t mature enough to fight off infection.
“Most enteroviruses cause a very mild disease in the children that they infect,” Dr. Mike Ryan, the executive director of the World Health Organization’s health emergencies program, said in a briefing Wednesday. “But in a small proportion, we see a much more significant, catastrophic disease.”
In May, the WHO called attention to a cluster of a particular type of enterovirus, called echovirus-11. Nine babies in France within their first month of life had been infected and developed organ failure and sepsis. Seven died.
That is more than would be expected, a WHO spokesperson wrote in an email. “It is considered unusual due to the extremely rapid deterioration and associated case fatality rate amongst the affected babies,” the spokesperson wrote. Echoviruses can be spread by fecal matter or by breathing in respiratory droplets, and they usually live in the digestive system.
Twin baby boys in Italy were found to be infected with the same echovirus-11 strain. One was severely sickened and remained in intensive care. What’s more, health officials in the United Kingdom reported a similarly unusual increase in severe myocarditis, or heart inflammation, among 10 babies who had another enterovirus called coxsackievirus. At least one died.
The WHO is expected to update global reports of enterovirus-related neonatal sepsis later this week, a spokesperson said Wednesday.
There is no way to know whether those specific strains are already in the U.S. and sickening babies. The Centers for Disease Control and Prevention doesn’t have an active reporting system for neonatal enteroviral disease or enteroviruses in general. More than 100 types of enteroviruses can infect people, according to the CDC.
“Although we do not have routine surveillance of enteroviruses, CDC does have other surveillance systems that we use to monitor and quickly assess signals for outbreaks and increases in specific types of enteroviruses,” Dr. Janell Routh, the head of the CDC’s division of viral diseases, said in a statement. “Given that viral circulation has been disrupted by the COVID-19 pandemic, we remain vigilant to any changes in enterovirus transmission.”
Summer is enterovirus season
Doctors interviewed across the country are seeing a small increase in enterovirus cases, especially among children. Most run a slight temperature, cough, sneeze or have a sore throat, and they recover without much fuss.
“We’re hearing reports from around the country of all of our children’s hospitals having some degree of significant enterovirus this summer,” said Dr. Buddy Creech, a pediatric infectious disease doctor at Vanderbilt University Medical Center in Nashville, Tennessee.
The cases in Europe, however, have prompted Creech and his colleagues to make sure pediatricians and families with newborns are aware of the potential for enteroviruses.
“We have our systems on high alert,” Creech said.
Though enteroviruses are common, cases of neonatal enteroviral sepsis have historically been rare. But because the pandemic threw all viral activity off, the concern is there could be an even greater surge in enteroviruses this summer.
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When more enterovirus is circulating in a community, the chance a newborn will become infected increases.
That’s why it’s critical for pediatricians to be on the lookout for the potential for severe illness in newborns, rather than “be behind the eight ball when things pick up and get out of control,” said Dr. Kevin Messacar, a pediatric infectious disease specialist at Children’s Hospital Colorado in Denver.
Creech’s team is already treating more newborns hospitalized with enteroviruses than usual. The hospital system didn’t comment on the exact number.
“These are typically children in the first few days or week or two of life who are exposed to an enterovirus and for reasons that we don’t fully understand get very sick from what typically causes nothing more than coldlike symptoms,” Creech said.
The babies are usually born healthy and go home from the hospital with their families. It’s then that they develop symptoms of enterovirus exposure, including:
- Fever.
- Not feeding well.
- Trouble breathing.
- Being extra fussy or cold to the touch.
- Pale or blotchy skin.
A few may develop severe complications: meningitis, organ failure, myocarditis, even problems within their bone marrow. Some babies’ tiny systems become “super inflamed” to the point that as much damage is being done by their immune responses as by the virus itself, Creech said.
Testing and treatment for enterovirus
Enterovirus treatments are limited. Babies get supportive care, such as intravenous fluids or help with breathing and blood pressure.
Many doctors also give the babies intravenous immunoglobulin. That’s essentially a cocktail of antibodies meant to bind to whatever virus is causing illness. Ideally, those antibodies work to calm inflammation and help prevent the virus from continuing to spread in the body.
No antiviral medicine is approved to treat those tiny babies.
“It is disheartening that we don’t have more treatments,” said Dr. Shannon Ross, an infectious disease specialist at Children’s of Alabama in Birmingham. Ross has treated one infant this summer with viral sepsis. “That’s the most difficult thing: having fewer options to treat these babies.”
It isn’t known which type of enterovirus led to severe disease in the babies cared for by Creech and Ross. Hospital systems don’t usually do that kind of testing, because doctors say it wouldn’t make a difference in how they’re treated.
In fact, it is difficult to get a true scope of the number of newborns who die or are hospitalized from enterovirus infection, because the U.S. doesn’t track such cases.
One research project aims to provide some clarity.
Kimberlin, of the University of Alabama at Birmingham, and Dr. Mark Abzug, a pediatric infectious disease physician at Children’s Hospital Colorado in Denver, launched a study in 2020 to analyze tissue samples from babies with neonatal enteroviral sepsis.
“One thing that we’re looking at specifically is to see if there are any viral laboratory or clinical markers that correlate well with morbidity and mortality,” Abzug said. It may turn out, for example, that the amount of virus circulating in the babies’ bloodstreams may be a flag that they are at risk for more severe illness.
That’s just a theory for now. The team will eventually sequence multiple strains of the viral samples — there are more than 110 — to learn more about how each affects newborns’ immature immune systems. The study has funding from the National Institutes of Health.
The ultimate research goal, Abzug said, is to find an effective antiviral medication.
“That’s the real unmet medical need. To do that, we are trying to prospectively gather the information that can inform the best study design for an antiviral as it becomes available for study,” Abzug said.
Answers are still a way away; just 23 babies have been enrolled so far. But the research is applauded by the doctors who treat those sickest of infants.
Enteroviruses are “underrecognized as a major player in the infectious disease world, partly because they’ve always been endemic,” Messacar said. “They’ve always been around.”
But they are also “one of the most common causes of meningitis, brain infections, heart infections and neonatal sepsis in our young babies,” he said. “We need to wake up to enteroviruses’ being a major cause of morbidity and, unfortunately, mortality in the pediatric population.”
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