Do common viruses suddenly cause liver failure in children?

Last October, a girl with severe and abnormal liver failure was admitted to a hospital in Birmingham, Alabama. Her symptoms were typical: her skin with her jaundice and her eyes were yellow, and her liver damage markers were off the chart.But she did a negative test on all the usual suspects behind her Liver disease.. Her only positive test was, surprisingly, for adenovirus, the most well-known and common virus that causes mild colds, conjunctivitis, or gastroenteritis. In rare cases, it may be associated with hepatitis or liver inflammation in immunocompromised patients. But this girl was healthy.

Then it happened again. The second child was about the same age, all with the same symptoms, and again positive for adenovirus. “One patient is a fluke. Two are patterns,” said Markus Buchfellner, a pediatric infectious disease doctor at the University of Alabama at Birmingham (UAB). The two soon became three, then four.Surprisingly, hospital doctors warned local health authorities and the CDC, and the investigation finally ended up. 9 such cases Abnormal hepatitis in children in Alabama. Two necessary liver transplants.

Buchfellner initially thought that everything that was happening was local to Alabama.But this Spring, British researchers have begun to independently be confused about their own mysterious rise in hepatitis among children.Since then they have 150 such cases In the UK, this has caused the CDC to throw a wider net, resulting in a suspicious number of cases across the United States. Up to 109.. Fifteen children needed a liver transplant and five died.Globally, the number of possible cases is currently total Spread to 20 countries 348..

Early evidence continues to point to an association with adenovirus. This is an unexpected correlation that is too strong to dismiss and not strong enough to close the case. 70% of the world’s possible cases have been tested positive for adenovirus. According to the World Health Organization.. However, biopsies were performed in only a few of these cases, but the adenovirus could not be found in the liver of the child. At the same time, there is no doubt that another virus has recently infected a large number of children. Of course, it is SARS-CoV-2. However, the correlation here is even less clear. Of the possible cases, only 18 percent were tested positive for COVID.

Adenovirus and coronavirus are not necessarily mutually exclusive explanations. The main hypothesis now suggests an interaction between adenovirus and a pandemic. This is because social distance changes the pattern of adenovirus immunity, making it more serious or simple. more Because adenovirus infections, or previous infections or co-infection with coronavirus, cause an abnormal response to adenovirus. Or has the adenovirus itself changed recently and evolved to damage the liver more easily?

Severe liver failure in children is extremely rare, says Helena Gutierrez, medical director of pediatric liver transplantation at UAB and Children’s of Alabama. But when that happens, a significant proportion of cases remain completely mysterious even in peacetime.In most cases, no identifiable cause was found Half of a child Liver failure is so severe that a transplant may be needed. Ultimately, understanding recent patterns of unexplained liver failure cases in children may shed light on previously mysterious cases that were once too rare to receive much attention. Hmm.

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But why is it increasing now? Children under the age of 5 who make up the majority of hepatitis are not yet vaccinated, so the only cause that can ultimately be ruled out is the COVID vaccine. In the coming weeks, experts will review three key data to analyze the remaining hypotheses.

The first and perhaps most obvious datasets to collect are: Have these children been infected with COVID before? The overwhelming majority of children with hepatitis have been tested negative for the coronavirus, but researchers are currently collecting antibody data to see if any of them had COVID in the past. .. “I don’t think it’s directly related to the virus itself,” says Buchfellner, but perhaps COVID infections make children more susceptible to liver failure when something else happens, such as an adenovirus infection. You may have done so.And but Multisystem inflammatory syndrome, or MIS-CAfter coronavirus infection May affect the liverHepatitis patients showed no other characteristics Signs of that conditionHigh inflammatory markers and heart damage.

Many children will be positive when COVID antibody data is available. This is because many children are generally recently infected with COVID. Experts will want to go one step further to determine if the coronavirus actually plays a role. If so, they would expect that children with hepatitis are more likely to have COVID antibodies than controls in children without hepatitis.

Read: The impact of COVID-19 on children is even stranger than we thought

The second important piece of data is about the adenovirus itself. Adenovirus is very common, but do all positive tests simply reflect an accidental infection unrelated to liver failure? Again, researchers will want to see if children hospitalized for hepatitis are more likely to test positive for adenovirus than children hospitalized for other reasons. If so, the link to adenovirus will be stronger. The UK is analyzing these accurate data and expects results next week.

Exactly how many children are positive for adenovirus sounds like simple statistics, but when investigators are dealing with almost retroactive data, it can be annoying at an early stage. I have. Different doctors in different hospitals may consider ordering different tests. UAB happened to test for adenovirus, but the test is not always routine, as it is so few on the list of causes of hepatitis. Benjamin Lee, a pediatric infectious disease doctor at the University of Vermont, says how the test is done can affect whether the test returns positive. “Can a virus be detected in the blood when a patient comes to the hospital for treatment? Are there other sites that need to be tested?” He asks. How about your nose and throat? Or a stool? And in fact, British researchers needed to understand the melange of blood, stool, and respiratory samples with different positive rates.

The third prong of the study focuses on the adenovirus found in these samples. By sequencing their genomes, it is possible to determine if the virus has recently acquired a new mutation that could explain the link to liver failure. Subspecies of adenovirus have previously emerged, and this type of virus is particularly suitable for reconstructing its genome. British scientists initially struggled to get enough virus out of early samples, but whole-genome sequencing is underway. And scientists don’t have a large database of old adenovirus samples of this kind for comparison with new ones. “We take it for granted with SARS-CoV-2,” says James Platts-Mills, an infectious disease physician at the University of Virginia. Therefore, the initial progress may be slow.

However, partial sequencing of the viral genome has already identified one particular type of adenovirus that predominates in cases of hepatitis. It is adenovirus 41, also known as 41F. (There are more than 100 types of adenovirus. F refers to the species, and the numbers reflect the order in which the types were discovered.) Adenovirus 41 infects the gastrointestinal tract. Platts-Mills is studying adenovirus 41 in developing countries Main causes of hospitalization Because of diarrhea in children. It is also distributed in wealthy countries, but in the United States it does not cause enough problems to justify active surveillance. According to Platts-Mills, hepatitis cases may be just the “tip of the iceberg” of 41 cases of a large number of undocumented mild adenoviruses. The invisible surge, if any, may be due to a new viral mutation or a large number of infants being infected at once and the COVID restrictions being relaxed.

Still, it’s amazing that adenovirus 41 is especially seen as a suspect in these hepatitis cases, adenovirus experts told me.Adenovirus is associated with severe liver failure, but type rather than adenovirus 41 1, 2, 3, 5, and 7.. In addition, these cases most often occur in patients with a depressed immune system. “In children with weakened immunity, we could see it in the liver. When we made the slides, we could see the viral particles,” said Kurt Schaberg, a pathologist at the University of California, Davis. Says. Adenovirus hepatitis.. The dark center of infected hepatocytes grows and swells. It’s all very obvious. Biopsy did not find these patterns in the liver of children with unimmunized immunity. If adenovirus plays a role, it is probably more indirect. Perhaps it somehow triggers the immune system to begin attacking the liver on its own, or in combination with other viruses, toxins, or environmental factors. And since this can continue even after the virus itself has been removed, the adenovirus test can be negative.

This all means that it is not easy to understand the answers to these cases of hepatitis in children. “If you find the virus in your liver, that’s it,” says Buchferner, Alabama. “The fact that it can’t be found means it’s much harder to prove.” Rather than a single direct cause, researchers are probably looking for an indirect cause or multiple indirect causes. I am. In the coming weeks, at least by clarifying three important questions: whether these children are also infected with COVID, whether the adenovirus infection is accidental, and whether the virus is mutated. You can narrow down the list of plausible hypotheses.

Meanwhile, all nine children in Alabama have recovered. Whatever the cause, the doctor emphasized to me, but the risk of severe hepatitis for a healthy child is still very small.