Within the GEN-COVID Multicenter Study, biospecimens from more than 1,000 SARS-CoV-2-positive individuals have thus far been collected in the GEN-COVID Biobank (GCB). Sample types include whole blood, plasma, serum SERO, leukocytes, and DNA. The GCB links samples to detailed clinical data available in the GEN-COVID Patient Registry (GCPR). It includes hospitalized patients (74.25%), broken down into intubated, treated by CPAP-biPAP, treated with O2 supplementation, and without respiratory support (9.5%, 18.4%, 31.55% and 14.8, respectively); and non-hospitalized subjects (25.75%), either pauci- or asymptomatic TRANS. More than 150 clinical patient-level data fields have been collected and binarized according to the organs/systems primarily affected by COVID-19: heart, liver, pancreas, kidney, chemosensors, innate or adaptive immunity, and clotting system, for further statistics. Hierarchical Clustering analysis identified five main clinical categories: i) severe multisystemic failure with either thromboembolic or pancreatic variant; ii) cytokine storm type either severe with liver involvement or moderate; iii) moderate heart type either with or without liver damage; iv) moderate multisystemic involvement either with or without liver damage; v) mild either with or without hyposmia HP. GCB and GCPR are further linked to the GEN-COVID Genetic Data Repository (GCGDR), which includes data from Whole Exome Sequencing and high-density SNP genotyping. The data are available for sharing through the Network for Italian Genomes, within the COVID-19 dedicated section. The study objective is to systematize this comprehensive data collection and start identifying multi-organ involvement in COVID-19, defining genetic parameters for infection MESHD susceptibility within the population, and mapping genetically COVID-19 severity and clinical complexity among patients.