Lockdown cause of childhood hepatitis

Serious hepatitis outbreak in children, immunity was NOT generated as normal in locked down children and now the specific viral cause has just been discovered

Since 20th March

Children under 16

35 countries

UK, 12 liver transplants, Ireland 2

Immunosuppressant drugs for life

No single virus had been identified in all cases

Hepatitis viruses A, B, C, E not detected in cases

No link to current covid infection status

Most / many cases were not covid vaccinated

Symptoms of hepatitis

Any one of the classic 3

Pale, grey-coloured stools

Dark urine

Jaundice

Other symptoms include

muscle and joint pain

fever

feeling and being sick

feeling unusually tired all the time

a general sense of feeling unwell

loss of appetite

tummy pain

itchy skin

A post lockdown phenomena?

Two common viruses, spreading again after pandemic lockdowns

infants exposed later than normal

Detailed investigation, 9 early cases and 58 control subjects

Median 3.9 years, 4 boys, 5 girls

Preceding subacute history

Abdominal pain, diarrhoea and vomiting,

between 1 to 11 weeks prior to acute hepatitis

Using sequencing and real-time PCR

Adeno-associated virus 2 (AAV2),

detected in the plasma of 9/9

and liver of 4/4 patients

(normally causes no illness, requires a coinfecting "helper" virus)

Age-matched healthy controls

Adeno-associated virus 2 (AAV2),

detected in the plasma of 0/13

Children with adenovirus (HAdV) infection and normal liver function

Adeno-associated virus 2 (AAV2),

detected in the plasma of 0/12

Children admitted to hospital with hepatitis of other aetiology

Adeno-associated virus 2 (AAV2),

detected in the plasma of 0/33

AAV2 typically requires a coinfecting ‘helper’ virus to replicate

Usually adenovirus (HAdV) or a herpesvirus

Adenovirus (HAdV)

Detected in 6/9 cases

Human herpesvirus 6B (HHV6B)

Detected in 3/9 cases

Conclusion

Acute non-A-E paediatric hepatitis is associated with the presence of Adeno-associated virus 2 (AAV2) infection,

which could represent a primary pathogen or a useful biomarker of recent Adenovirus (HAdV) or Herpesvirus (HHV6B) infection.

Prof Judith Breuer, University College London and Great Ormond Street Hospital

During the lockdown period when children were not mixing, they were not transmitting viruses to each other.

They were not building up immunity to the common infections they would normally encounter.

When the restrictions were lifted, children began to mix, viruses began to circulate freely - and they suddenly were exposed with this lack of prior immunity to a whole battery of new infections.

Prof Emma Thomson, University of Glasgow

Larger studies are urgently needed to investigate the role of AAV2 in paediatric hepatitis cases.

We also need to understand more about seasonal circulation of AAV2, a virus that is not routinely monitored,

it may be that a peak of adenovirus infection has coincided with a peak in AAV2 exposure,

leading to an unusual manifestation of hepatitis in susceptible young children

Class II HLA-DRB1*04:01 allele

Identified in 8/9 cases (89%)

(background frequency of 15.6% in Scottish blood donors)

Adeno-associated virus 2 (AAV2) mutations

May be significant

9 capsid gene mutations over-represented in these cases

altered phenotype, including substantial evasion of neutralising antibodies directed against wild-type AAV2,

enhanced production yields,

increased virion stability.