Scientists believe they have found a plausible explanation for the unusually high number of cases of severe acute hepatitis of unknown etiology in pediatric patients in the UK and worldwide.[1,2]
Two independent studies published on the preprint server suggested that association with adenovirus and adeno-associated virus type 2 (AAV2), and less commonly herpes virus 6 (HHV6), was responsible for the increase in cases of severe acute hepatitis of unknown etiology. It is possible in pediatric patients.
The researchers noted that they found no evidence that the outbreak in the UK, as of 4 July, affecting 263 pediatric patients, most of whom were under the age of 5, was directly linked to SARS-CoV-2 infection.
a study was led by University of Glasgow, in Glasgow, and by another Great Ormond Street Hospital from london, Both in the UK. None have been peer reviewed and are available on preprint servers.
Sequencing and Metagenomics
The Glasgow study investigators conducted a detailed examination of 9 initial cases compared to 58 control subjects. Using next-generation sequencing and real-time polymerase chain reaction (PCR), they confirmed the presence of adeno-associated virus type 2 in the plasma of 9 cases of acute-onset hepatitis and in the liver of 4 patients analyzed. . Adeno-associated virus type 2 was absent in all control groups, which included age-matched healthy individuals, children with adenovirus but normal liver function, and children hospitalized with hepatitis of other etiology.
Using metagenomics and adenovirus sequencing, the London study examined 28 cases, including liver samples from 5 pediatric patients who needed a transplant and blood samples from the remaining children who did not. RNA sequencing of liver samples confirmed the presence of adeno-associated virus type 2 replication in the liver of children with sudden-onset hepatitis. Patient samples were also compared with 132 control samples from immunosuppressed and immunocompetent patients. The results showed that adeno-associated virus type 2 was present in only 6 out of 100 pediatric patients who did not have hepatitis and still had very low levels (11 out of 32), even in patients with immunosuppression. In too.
immunity decreased after lockdown
Adeno-associated virus type 2 requires a co-infecting ‘helper’ virus, usually a human adenovirus or human herpesvirus type 6b (HHV6b), to replicate normally.
Although neither team was able to say for sure why the outbreak of severe acute hepatitis of unknown etiology occurred in pediatric patients this year, they speculated that the increase in adenovirus infections following the end of the COVID-19 pandemic restrictions There may be a decrease in immunity. Certain viruses and changes in virus circulation patterns in children.
Emma Thomson, clinical professor and consultant in infectious diseases, MRC- University of Glasgow Center for Virus Researchwho led the Scottish study, said: “Adeno-associated virus type 2 may itself cause disease or it may be a useful biomarker of recent adenovirus infection, which may be the main underlying pathogen, but is more difficult to detect. There are many unanswered questions and larger studies are urgently needed to investigate the role of adeno-associated virus type 2 in pediatric hepatitis.”
“We need to understand more about the seasonal circulation of adeno-associated virus type 2, a virus that is not monitored systematically; it may be that a peak in adenovirus infection is associated with adeno-associated virus type 2. corresponds with a peak in exposure, leading to unusual manifestations of hepatitis in susceptible young children,” the researcher said.
Both studies ruled out the possibility of recent or previous SARS-CoV-2 infection as a direct cause of acute hepatitis outbreaks. The researchers found no SARS-CoV-2 in the patients’ livers, while tests by the Glasgow team found that only two-thirds of the patients had antibodies to the virus, as did antibodies to SARS-CoV-2 in Scottish children. similar to the spread. those days. In addition, the spike in cases came after a spike in COVID-19 cases in Scotland, but soon after a spike in adenovirus infections, he pointed out.
Judy Breuer, Professor of Virology at the Children’s Health Institute Great Ormond Street Hospitalin London, said: “While we still have some unanswered questions about what exactly is causing this increase in acute hepatitis, we hope these results can reassure parents concerned about COVID-19.” because neither team found any direct link to SARS-CoV-2 infection.”
“However, our data point to adeno-associated virus type 2 in liver or blood cases as the strongest biomarker of hepatitis. In addition, the presence of human herpesvirus type 6b and adenovirus in the damaged, excised livers of five children.” necessary liver transplantation raises questions about the role of coinfection with these three viruses in the most severe cases,” she concluded.