Dr. Matt Binnicker, an expert in diagnosing infectious diseases, provides an update on the global outbreak of hepatitis in young children and discusses the possible causes being investigated by scientists around the world, including the potential role of Covid-19.
During the fall of 2021, physicians in Alabama began to observe an unusual increase in the number of young children diagnosed with hepatitis inflammation of the liver, which can become a serious, life-threatening disease. First, 5 children were admitted to the Children of Alabama with symptoms of hepatitis, including yellowing of the eyes, jaundice, and an enlarged liver. Over the next 3 months, another 4 children were diagnosed, but each from a different part of the state and without any apparent epidemiological connection. The only common thread was that most had experienced an gastrointestinal or upper respiratory disease in the days before their hospitalization, and each of the patients was tested positive for adenovirus.
Fast forward to May 2022 and the number of pediatric hepatitis cases has increased 450 globally. Eleven children are dead. In the United States alone, 109 cases across 25 states have been reported, with more than 90% of children requiring hospitalization, 14% requiring liver transplantation, and 5 dying. While the exact cause remains a mystery, more than 50% of children have been tested positive for adenovirus, suggesting that this common viral infection may be linked to the outbreak. However, researchers are also investigating other potential causes, such as Covid-19, or the possibility that Covid-19 precautions have reduced natural immunity to common viruses, such as adenovirus.
What is adenovirus?
Adenovirus are named from the tissue from which they were first isolated – they adenoids, which is the tonsil and lymph tissue where the nose and throat meet. There are more than 50 different types of adenoviruses that can cause disease in humans, and infection with one or more types is extremely common. Infection is usually caused by direct contact with airway droplets – cough or sneezing – or through the fecal-oral route (touching your mouth with unwashed, contaminated hands). In people with a normal immune system, infection generally results in a mild or asymptomatic course of the disease with common symptoms, including a respiratory disease (cough, sore throat, runny nose), conjunctivitis (eye infection) or gastroenteritis (diarrhea, vomiting). Historically, adenovirus infection in otherwise healthy people has not been associated with hepatitis.
Does adenovirus cause a global outbreak of hepatitis in children?
Because many of the early cases of hepatitis occurred in children who had recently experienced a respiratory or gastrointestinal disease, specific testing for adenovirus was performed and the virus was identified in the blood of these patients. Out of the 450 total cases to date, approx. 70% tested positive for adenovirus, and further studies have shown that the majority of these are adenovirus serotype 41, which is commonly associated with diarrhea and vomiting in infected individuals. Although these results seem to strongly suggest an association between adenovirus and hepatitis, liver biopsies performed in a subset of cases have shown no evidence of adenovirus infection, prolonging the mystery as to the cause of the outbreak.
Could Covid-19 be behind the onset of hepatitis in children?
Due to the lack of documented adenovirus infection in all reported pediatric hepatitis cases, significant efforts are being focused on investigating other potential causes. One possibility is that Covid-19, along with infection with another common virus – like adenovirus – can result in liver disease. In some patients, Covid-19 may hyperstimulate immune system and increases the chances that a subsequent viral infection can trigger harmful inflammation.
Another possibility is that Covid-19 alone may be behind the increase in cases of hepatitis in children. Covid-19 has been linked to a condition called multisystem inflammatory syndrome in children (MIS-C), and a recent examination found that children with Covid-19 have an increased risk of liver disease. However, only 18% of cases of hepatitis in children have shown laboratory evidence of active SARS-CoV-2 infection. Ongoing studies are examining whether children have Covid-19 antibodieswhich would suggest prior infection and strengthen the case that Covid-19 may be a contributor.
A third hypothesis is that the significant reduction in adenoviral infections during the Covid-19 pandemic due to measures such as masking, distancing, and lockdowns has resulted in decreased natural immunity in young children, increasing their susceptibility to infection – and potentially more serious disease. . Although possible, this hypothesis seems unlikely as cases have occurred in children up to 16 years of age. Older children are much more likely to have been exposed to adenoviruses and therefore have a level of natural immunity.
Over the next few weeks, new data from one case-controlled study in the UK should provide clearer insight into whether adenovirus infection is a random finding or has a causal relationship with hepatitis in children. Until then, parents and caregivers should be on the lookout for signs and symptoms of hepatitis in young children, including fever, abdominal pain, and yellowing of the eyes and skin.