WES profiling of COVID-19

Introduction: Italy has been the first European Country experiencing the epidemic wave of SARS-CoV-2 infection reaching 200,000 cases On March 16, we started the GENCOVID project (https://sites google com/dbm unisi it/gencovid) aiming to collect 2,000 COVID-19 patients all over Italy, the first 500 being already collected Material and Methods: A first cohort of 130 Tuscanian COVID-19 patients (100 of which hospitalised) was subjected to clinical and molecular characterisation by Whole Exome Sequencing (WES) Results: Searching for common genes by Collapsing Methods against 300 WES controls of Italian population failed to give straightforward statistically significant results with the exception of a pair of genes, one belonging to the Olfactory Receptor families with many paralogs in the genome This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factor with a strong underlying heritability (50%) Learning the lesson of Autism Spectrum Disorder, we started to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model We identified for each patient an average of 3 pathogenic mutations involved in virus infection susceptibility and pinpoint to one or more rare disorder(s);the number being higher in the most severely affected cases To our knowledge, this is the first report on WES and COVID-19 Our results pinpoint to a combined model for COVID-19 susceptibility with a number of, yet unknown, common susceptibility genes which represent the favorite background in which additional rare mutations confer to the host the best environment for virus growth and organ damage