Thread by @EckerleIsabella

Unknown #Hepatitis in #children: From my point of view as a clinical virologist, there are many aspects that speak against #Adenovirus, with important implications for treatment. Why? Viral loads in the cases reported to be low. Normally viruses causing hepatitis are massively

found in the blood. Hepatitis virus A, B, E, when causing fulminant clinical hepatitis: very high viral loads (C rarely causes this). Same for other viruses with hepatic tropism (eg Yellow fever). Viral hepatitis with pronounced clinical picture but low viral loads doesn’t exist

Now in the children with hepatitis no Adenovirus was detected in the liver biopsies, and viral load in blood was low. In some cases, Adenovirus DNA only in whole blood but not plasma. Again: a virus that is replicating in liver should be found everywhere: plasma, serum, biopsy

Strikingly, no full genome of an Adenovirus could be sequenced from any of the cases. In the rare cases of systemic Adenovirus infections that I remember (very few in > 10 years diagnostic virology at university hospitals, all in severely immunocompromised), huge viral loads,

so high that sequencing would be easily possible, also virus isolation in cell culture. The fragments detected in the affected children with hepatitis revealed in most (not all) Adv positive cases 41F. This is a long known gastrointestinal Adv that never caused hepatitis before

In absence of a full genome indicating anything unusual, hard to believe 41F would suddenly completely change tropism PLUS suddenly cause severe disease in immunocompetent children, which was never observed before - and all of this, on a global scale. Not all cases Adv + at all.

With no common pathogen across cases & increasing signals for a post-viral (immune-mediated) pathogenesis (whichever pathogen is the cause), important decisions for treatment: antiviral (only effective if there is virus replicating) vs immunosuppressive treated (eg cortison)

Rapid data sharing of successful treatment for post viral disease extremely important. Urgently needed what works, remember children are very sick, liver transplantation is only possible in highly specialised centres & several deaths are already reported in US.

Also data on adenovirus circulation from other parts of the world would be interesting. Many European regions experience high levels of Adv circulation. Typing is of interest as well as detection in whole blood in healthy children. Possible it’s just a coincidence finding

Since there were many comments on #SARSCoV2 #COVID19 as potential trigger: I think this is a likely hypothesis but more data needed. Serology data should come soon, I would assume such children will have close follow up for transaminases & serological assays are widely available