Genetic and immunological basis of severe SARS-CoV-2 infection

The purpose of the proposed project is to identify the key molecules and molecular pathways that underlie severe forms of SARS-CoV-2 infections.We have collected samples from several unique cohorts, including patients who have suffered from hypoxemic pneumonia, mucormycosis, multisystem inflammatory syndrome, and long COVID.

We are focusing on young/pediatric patients without comorbidities, hypothesizing that monogenic inborn errors of immunity may underlie severe viral infections in otherwise healthy individuals.

We will perform genetic analysis using whole exome/genome sequencing, immunological evaluation including measurement of viral-specific antibody response, autoantibody profiling, single-cell RNA and B-cell receptor sequencing, and additional relevant functional assays.The research will be carried out by four internationally recognized investigators with complementary expertise.

During the initial phase, which will last for 6-12 months, patient samples will be collected, and genomic sequencing will be performed.

Subsequently, immunological and other functional assays will be conducted.The project aims to identify the underlying molecular pathogenic mechanisms in patients with severe COVID-19, which could lead to better prevention strategies and more targeted therapies.

Additionally, the research pipeline we develop may serve as a model for how to approach the identification of the etiological factors, pathways involved, and therapy for future pandemics.