MIAMI — No unusual cases of severe hepatitis among children have been confirmed in Florida despite a global rise in cases and an ongoing investigation into what’s causing the outbreak, which has affected more than 500 kids worldwide, including more than 150 in the United States.
Doctors and public health officials in South Florida and elsewhere have been on alert for unusual hepatitis cases without a known cause since an April 21 advisory from the Centers for Disease Control and Prevention notified them of a cluster of severe cases in Alabama among previously healthy children dating back to October.
Since then the global count, including retrospective cases that are not new, has grown to at least 500 children in 20 countries, including 180 pediatric patients in the United States over the past seven months, an increase of 71 cases over the number reported two weeks ago, the CDC said on Wednesday.
Jeremy Redfern, press secretary for the Florida Department of Health, said state officials have been on the lookout for potential cases but that none have been confirmed to date.
“The Bureau of Epidemiology continues to monitor and will investigate any suspected cases that are reported to the Department of Health,” Redfern said in an email.
However, the CDC said on Wednesday that Florida has reported at least one person younger than 10 under investigation for severe hepatitis with unknown cause, though it may not be a recent case.
The CDC said it is investigating cases in 36 states and territories. Though most children have recovered, at least 5 kids have died and 16 needed a liver transplant.
Nearly half of the children identified by the CDC also have tested positive for adenovirus, a common bug among kids that usually causes severe stomach illness and pink eye. CDC officials are casting a wide net as they search for a cause but on Wednesday the agency said that adenovirus infection “continues to be a strong lead.”
Taking more precautions with patients
The agency has advised doctors to take extra steps when treating patients with unusual cases of severe hepatitis, such as testing for adenovirus infection and collecting blood, respiratory and stool samples.
“We’ve had potentially a handful of similar cases. Now, we’re going to be more aware,” said Dr. Aymin Delgado-Borrego, a pediatric gastroenterologist and hepatologist with KIDZ Medical Services, a physician group that works with Joe DiMaggio Children’s Hospital in Hollywood.
Though hepatitis cases in healthy kids are rare, it’s not unusual for the cause to be unknown when they do get the disease.
Hepatitis, which is an inflammation of the liver, can be caused by infection with hepatitis A, B, C, D and E viruses, or by some toxins and medications. Hepatitis C, which spreads through contact with blood from an infected person, can cause liver damage, including cirrhosis and cancer, if left untreated.
Investigating whether COVID connected to outbreak
Most of the children with severe hepatitis reported around the world did not have active COVID-19 and were unvaccinated. But the CDC said it is investigating whether SARS-CoV-2, the virus that causes COVID-19, is a possible cause of the outbreak.
At a World Health Organization press conference on Tuesday, Dr. Philippa Easterbrook, a senior scientist in the global hepatitis program at the WHO, said that researchers are investigating “how these two infections may be working together as co-factors either by enhancing susceptibility or creating an abnormal response.”
“There is some interesting communications in the scientific literature, raising a bit more about those mechanisms and about whether a previous COVID infection in children, perhaps some time ago, may have persisted and stayed around in the gut and then a subsequent adenovirus infection may have resulted in the immune system being activated and causing inflammation [of the liver],” Easterbrook said.
However, Easterbrook emphasized that this was just a hypothesis and that there was no data to support it.
Dr. Mobeen Rathore, a pediatric infectious disease specialist with the University of Florida Health System in Jacksonville, said researchers know that COVID-19 can cause hepatitis in adults but that the disease alone does not explain the sudden emergence of severe hepatitis in children.
“We don’t believe the 109 or so cases have been associated with coronavirus,” Rathore said. “What we do know for sure is there’s no reason to believe that any of these hepatitis cases have been caused by the vaccine.”
Researchers are investigating the potential link between prior COVID-19 infection and the unusual cases of severe hepatitis in children, but it will likely take months or more before they can identify the cause, and even longer to explain why some kids get it and others do not.
KIDZ Medical’s Delgado-Borrego said that during the past six months, four children — three 1-year-olds, and one 3-year-old — have presented at Joe DiMaggio Children’s Hospital with hepatitis and a confirmed adenovirus infection.
In recent months, Delgado-Borrego and her colleagues have also seen older pediatric patients with severe hepatitis and a history of recent Epstein-Barr virus or SARS-CoV-2 infection but did not test positive for adenovirus. She said doctors have wondered if there’s a connection.
“We cannot ignore the elephant in the room,” she said. “The question of a synergistic effect between COVID-19 and any other hepatotropic virus or any other injury to the liver is a very significant one. ... COVID-19 certainly affects the liver, and it is clear that when you have essentially two hits to the liver, it’s easy to develop more or significant inflammation.”
Warning signs of hepatitis
At Nicklaus Children’s Hospital in Miami, doctors have not admitted any pediatric patients with severe hepatitis and adenovirus infection in recent months, said Dr. Ruben Gonzalez-Vallina, a pediatric gastroenterologist and hepatologist.
Once doctors rule out a known cause for hepatitis, such as infection with hepatitis A, B, C, D and E viruses, they test the patient’s blood and stool for adenovirus, he said.
Gonzalez-Vallina said researchers are investigating a possible link between the hepatitis cases in kids and infection with a specific adenovirus called type 41, which typically causes gastroenteritis in children.
He said that so far there is no evidence that any cases of severe hepatitis in children were caused by COVID-19 or the vaccines, but that researchers are investigating a potential link to prior infection with SARS-CoV-2.
“We are looking back now on cases of severe hepatitis among people who were healthy to see if they have antibodies and if they were exposed to COVID-19 before,” Gonzalez-Vallina said.
As the number of severe hepatitis cases without a known cause continues to rise among children, Rathore of UF Health Jacksonville said parents should exercise common sense when considering whether to seek medical attention for their kids.
“A child with hepatitis can sometimes just start with a fever and not eating well and just not feeling well,” he said. “Any virus can do that, but the things that can potentially alert you beforehand are if the urine becomes dark, or the stool becomes light colored … or jaundice of the skin, or the eyes become yellow in tone.”
