In the months since UK doctors voiced their outcry over the mysterious incidence of smallpox that appeared to affect young children, researchers have been desperate to find the cause and possible link to the coronavirus epidemic among the leading theologians. But on June 17, researchers at the US Center for Disease Control and Prevention (CDC) published data suggesting that in the United States, at least levels of hepatitis, or inflammation of the liver, for unknown reasons had not changed since 2017 among children aged 11 or younger. If true, the findings may confuse the idea of linking the epidemic.
Not everyone is guaranteed by the data, however, and it is unclear whether the same acquisition will occur in other countries. “I can tell you, having worked in this country for 30 years as a liver doctor, we have had a large number of cases by 2022,” said Deirdre Kelly, a pediatric liver specialist at the University of Birmingham, UK. “And I think the United Kingdom’s conviction is very good.”
In addition to the US results, the CDC continues to assess potential links to the epidemic. An analysis published on June 24 showed that 26% of 123 children with undiagnosed hepatitis in the United States had a history of testing for COVID-19 prior to liver disease2. The CDC is now working on collecting the samples it needs to test its antibodies against SARS-CoV-2, to find out if some children with hepatitis had previous undiagnosed diseases, said David Sugerman, chief medical officer at the Infectious Diseases Unit. at the CDC National Vaccination and Respiratory Centers. “We are very much looking at SARS-CoV-2,” he said.
Known and unknown causes
Hepatitis in children has many known causes, including infection with hepatitis A, as well as exposure to certain drugs, such as paracetamol. But every year, a few cases of undiagnosed childhood hepatitis occur.In early April, the United Kingdom Health Security Agency (UKHSA) informed the public of an increase in the number of young children with severe hepatitis. At the time, the organization reported that there may be 60 cases of children under the age of 10 by 2022. Doctors often see about 20 such cases a year in the United Kingdom, says Kelly.
Since the beginning of this year, more than 250 children in the UK have hepatitis – and, on May 26, a total of about 650 cases in 33 countries have been reported to the World Health Organization. Twelve British children needed reassurance; no one is dead. In the United States, 11 of the 296 children diagnosed with the disease have died.
In the United Kingdom and the United States, many children with undiagnosed hepatitis were also infected by a member of a family of common viruses known as adenoviruses. This has led to speculation that hepatitis is caused by adenovirus. But while this is a popular UKHSA theory, it is not very popular. Researchers have shown a lack of statistical control: adenovirus infections are most common in winter and spring, and it is not known what the infection rate was among children who did not have hepatitis.
There is also a lack of precursors: adenoviruses are not known to cause hepatitis in children with healthy immune systems. And the levels of the virus found in most children with hepatitis are low. “I do not think it is an adenovirus,” said Orit Waisbourd-Zinman, a pediatric liver specialist at Schneider Children’s Medical Center in Petah Tikva, Israel.On June 10, Waisbourd-Zinman published a series of cases of five children with undiagnosed hepatitis3. Only one of them, he says, was diagnosed with adenovirus. Microbiologist Sumit Rawat at Bundelkhand Medical College in Sagar, India, tested samples of 17 children with unexplained hepatitis and found only 3 adenoviruses.
But Waisbourd-Zinman and Rawat both say that all the children they see have been tested for SARS-CoV-2 before, or have family members with them. UKHSA re-listed COVID-19 as a possible explanation. However, only 15% of UK children with hepatitis virus became infected with SARS-CoV-2 at the time of diagnosis, and the organization did not release data on how many antibodies against the virus, which could exacerbate previous infections.
COVID connection
Although there are no definite theories yet, the timing of the outbreak of hepatitis strongly indicates a strong connection with the epidemic, says infectious disease doctor William Irving at the University of Nottingham, in the UK. Increased cases may be the result of direct damage resulting from previous SARS-CoV-2 infections, reduced exposure to viruses during closure or abnormal immune response caused by coronavirus. “All of this is shaking hands,” he says. “But I think the COVID epidemic should be a serious one.”
One thing that is clear is that this condition is not related to the COVID-19 vaccine: only a handful of children in the United Kingdom have contracted hepatitis B vaccine. The CDC study, which covers the year 2017-22, asks for any explanations for the epidemic. The team collected data from health care records, organ transplant records and laboratory tests for adenovirus stool samples. Finally, the researchers found no recent increase in the number of cases of pediatric hepatitis, implants or adenovirus-positive cell samples.
Hidden diagnostics
But Waisbourd-Zinman argues that a simple analysis of electronic health records may not reveal the true rates of undiagnosed hepatitis in children. He tried similar research in Israel, he said, but soon discovered that he had to keep personal records in order to obtain a buried diagnosis. For example, one hepatitis was diagnosed as a result of drugs used in kidney transplants; another was infected with a known virus that causes hepatitis. These causes were not coded that way on medical records, and a temporary examination would be associated with unexplained cases of hepatitis.
He says that noise makes it difficult to choose cases that are not really defined. “It’s just impossible to see the increase,” he said. “It’s very different.” In April, researchers re-determined that undiagnosed hepatitis rates in large European children were no higher than the base of that region4. But Kelly, who interviewed the analysis, notes that there were limitations: as in the United States, the details of European health care are varied, he says, and the European survey includes only specialized hospitals.
Some countries, including Israel and the United Kingdom, have now asked doctors to report cases of pediatric hepatitis that could be explained by known causes to public health authorities, to help track the situation. This, along with a variety of research studies presented to trace the cause of the condition, could shed light on a number of unexplained cases of pediatric hepatitis that occur each year – whether they are linked to COVID-19 or not, Kelly said. “I think there may be something special about those children that puts them at risk,” he said. “Perhaps one of the best things about this is that we can find out what that is.”
