Acute hepatitis in kids. We urge colleagues with access to samples (blood/liver tissue) to consider SARS-CoV-2 superantigen-mediated disease, potentiated by a second virus (AdV) 🧵1/ thelancet.com/journals/langa…
2/ @ArditiMd and colleagues first described a superantigen motif in SARS-CoV-2 and several groups have independently found T-cell skewing (TRBV11-2 expanded) in kids w #MISC, indicative of a superantigen-mediated inflammation.
3/ Multiple reports have reported intestinal SARS-CoV-2 persistence and leakage of superantigens into the bloodstream trigger immune activation and possibly MIS-C in susceptible individuals, @LaelYonker et al
4/ A recent energy allocation theory could explain mild COVID-19, viral persistence and MIS-C specifically in growing children and young people: cell.com/action/showPdf…
5/ Adenoviruses (AdV) sensitises mice to superantigen (Staph. SEB) mediated disease. AdV + SEB triggered acute hepatitis in mice, while AdV or SEB alone did not cause hepatitis: journals.asm.org/doi/full/10.11…
6/ We should urgently investigate SARS-CoV-2 superantigen mediated disease, potentiated by an intestinal virus (AdV or other) as a possible mechanism of hepatitis. If confirmed, immunomodulatory treatments could be given and hopefully help.
🚨New paper alert! Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe #LongCOVID a thread 1/6.medrxiv.org/content/10.110…
2/6. To maximise our chances of understanding mechanisms of disease we enrolled the 121 most severe cases among >1000 patients screened.
3/6. A key observation in #longCOVID is elevated IgG responses to SARS-CoV-2 which normally wane off but imply persistent antigen (viruses) in these patients.
Brilliant special issue @ScienceMagazinescience.org/doi/10.1126/sc…. I discuss the establishment of immune-microbe interactions early in life and its importance for long-term health, Brief 🧵:
1/ In 1989 Lee & Len Herzenberg proposed a layered model of hematopoiesis. In 2021 @DanBunis@trevorDBurt et al showed fetal-to-adult transition to be highly variable among human newborns at birth: doi.org/10.1016/j.celr…
2/ This implies that newborns face postnatal microbes with a different balance of immune cells poised towards tolerance (fetal origin) and resistance (adult origin). This could have important implications for the establishment of immune-microbe mutualism early after birth...
How come #COVID19 is mostly mild in children? and at the same time, why do the rare hyperinflammatory syndrome #MISC affect mostly young people, and not the elderly? thread🧵and a hypothesis: cell.com/immunity/fullt…
2/In other infections, ex mononucleosis, symptomatic disease in teenagers differs from mild/asymptomatic infection in young children by stronger bystander T-cell activation and systemic inflammation.
3/But what limits systemic inflammatory responses in young children? One likely explanation is that energy allocation for growth increases the threshold to mount expensive systemic inflammatory responses unless absolutely required...
New work from our team and collaborators: The Immunology of Multisystem Inflammatory Syndrome in Children with #COVID19 (MIS-C) medrxiv.org/content/10.110… 1) we contrast MIS-C with Kawasaki disease and mild SARS-CoV2 in kids
2) MIS-C differ from hyperinflammation in severe COVID-19 disease
3) Unique cytokine profiles in MIS-C that differ from Kawasaki disease (pre-SARS-CoV2)