Mysterious Hepatitis Outbreak in Children in 2022, Study Suggests Linked to Common Pediatric Respiratory Virus

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occurrence of Acute severe hepatitis of unknown cause Infections in previously healthy children in 2022 may be associated with adeno-associated virus 2, or AAV2, according to the WHO. 3 independent studies It was published in Nature on Thursday.

Between April and July 2022, more than 1,000 children worldwide (at least 350 in the United States) were diagnosed with hepatitis. Nearly 50 need liver transplants, 22 children died, According to the World Health Organization.

New research suggests that AAV2 may be involved in this disease. This common childhood virus cannot copy itself unless another “helper” virus, such as adenovirus or herpes virus, is present. Researchers found that AAV2 was present in nearly all children with acute hepatitis of unknown origin, many of whom were infected with multiple helper viruses.

Although researchers cannot say for sure, the timing of the outbreak may be related to the easing of Covid-19 pandemic restrictions globally after a period of relative isolation.

“Children were either suddenly exposed to a barrage of viruses after the lockdown, or their immune systems were not sufficiently trained, making them more susceptible to harmless viruses,” said a German gastroenterologist not involved in the study. Physician Dr. Frank Tutke writes: An editorial published alongside new research.

In one new study that analyzed tissue samples from US children, AAV2 was detected in 93% of 14 cases, but only 4% of 113 controls. The researchers found that all AAV2-infected children were co-infected with a “helper” virus (human herpesvirus 6 or Epstein-Barr virus) that may facilitate AAV2 replication.

“Our results suggest that co-infection with AAV2 may cause more severe liver disease than infection with adenovirus or herpesvirus alone,” the authors wrote.

A second study conducted in the UK reported high levels of AAV2 in 96% of 28 affected children and only low levels in controls. Low levels of human adenovirus and human herpesvirus 6 were most often found in the liver, which the authors speculate may have similarly enabled AAV2 replication and liver damage.

A third study suggests that aberrant immune responses may promote AAV2 liver injury. British researchers found high levels of her AAV2 in blood and liver samples in 81% of her 32 affected children and low her in 7% of her 74 unaffected children. detected only AAV2 levels of Ninety-three percent of the affected group had genetic mutations that predispose them to autoimmune diseases involving her T cells, a type of immune cell.

Scientists once believed A human adenovirus, which usually causes mild cold and flu-like illnesses, may be the cause of the outbreak. However, adenoviruses usually only affect people with very weak immune systems, and various strains have shown that no single strain of virus can explain the outbreak, calling this hypothesis into question.

The new findings “are likely to be controversial and have implications for disease management,” said Tacke.

Elucidation of the mechanism is important for treatment. Antivirals are appropriate if AAV2 is the cause. Drugs that weaken the immune system may be needed if the cause is an abnormal immune response.

Although consistent findings across two continents provide strong evidence, some uncertainties remain, such as whether AAV2 directly causes liver injury or is ‘just a bystander’.

For example, adeno-associated viruses are commonly used as vehicles for gene therapy because they cannot replicate on their own. Liver damage has been observed in trials involving AAV-based approaches, but it’s rare and generally not fatal, scientists say.

“If AAV2 directly caused hepatitis, we would expect more cases to be reported,” Tacke said.

more Research is needed to understand how AAV2 infection alone, or with another virus, affects liver cells, he recommended.

“Until then, monitoring AAV2 (and related viruses) is recommended in such cases.” He said.