From the identification of pathogenic autoantibodies in patients with neurological post-acute sequelae of COVID-19 to mechanisms of neuronal-derived neoantigen production

In this project, we aim at investigating the biological basis of the neurological post-acute sequelae of COVID-19 using two experimental paradigms. In the first part, we will address the presence of autoantibodies, in the serum of long neuro-COVID patients, endowed with binding properties to central nervous system (CNS) antigens and able to impair CNS functions. Once the antibody-antigen binding has been demonstrated in vivo (in animal model) and ex vivo (on human CNS tissues), the targeted antigen.s will be identified using wide-proteome analysis. In the second part, we will study whether SARS-CoV-2 infection induces the RNA-editing mechanisms (i.e. ADAR and APOBECs enzymes known to be upregulated in epithelial cells following SARS-CoV-2 infection) in brain organoids and consequently promote the generation of neuronal-derived neoantigens. This part will include the identification of endogenous edited transcripts candidates, as well as their ability/affinity to be loaded on MHC class I molecules