Résilience - COVID-19 - Résilience - Coronavirus disease 2019

Single gene inborn errors of immunity underlying SARS-CoV2-related multisystem inflammatory syndrome in children. – GenMIS-C

Submission summary

Since April 2020, a rare and life-threatening SARS-CoV2-related Kawasaki-like disease, designated by the CDC as Multisystem Inflammatory Syndrome in Children (MIS-C), emerged in communities with high rates of COVID-19, in particular in children. Available epidemiological data provided compelling evidence for SARS-CoV2 being the trigger of MIS-C. We have previously identified a number of monogenic inborn errors of immunity (IEIs) underlying a variety of severe viral diseases including critical COVID-19 pneumonia. We now aim to dissect the immunopathogenesis of MIS-C by testing a monogenic hypothesis. We have recruited >500 previously healthy MIS-C patients, and are performing whole exome sequencing (WES) and whole genome sequencing (WGS) sequentially for them. We will search for rare single gene IEIs underlying MIS-C via an unbiased genome-wide approach, by analyzing the WES and WGS data at the cohort population and individual patient levels, testing models of genetic and immunological homogeneity and heterogeneity. For all candidate MIS-C-causing genes, we will perform in-depth characterization at the molecular and cellular levels, to connect the candidate genotype to molecular mechanism(s) and cellular phenotype(s) relevant to the MIS-C pathogenesis. This project will enable us to better understand the immunopathogenesis of MIS-C. The results of this project will also permit genetic diagnosis and counseling, while facilitating the development of novel preventive and therapeutic strategies in both genetic and non-genetic cases.

Project coordination

Shen-Ying Zhang (INSTITUT DES MALADIES GÉNÉTIQUES (IHU))

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IMAGINE INSTITUT DES MALADIES GÉNÉTIQUES (IHU)

Help of the ANR 79,970 euros
Beginning and duration of the scientific project: April 2021 - 12 Months

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