Genomic epidemiology and phylogenesis of SARS-CoV-2 in Italy: identification and characterization of circulating variants of clinical and public health relevance

The evolutionary rate of SARS-CoV-2 has been estimated to be around 2 mutations per month. This can explain the high variability observed among more than 400,000 genomes submitted to public databases and classified into more than 10 clades/subclades and several evolutionary lineages. Some mutations can affect proteins with important functions, like the Spike protein, generating viral variants potentially impacting key biological properties, such as an increased transmissibility, pathogenicity or the ability to escape immunological defences. To date, several SARS-CoV-2 variants have been described. The first relevant mutation was identified in position 614 of the spike protein (D614G) and became the main variant in the first phase of the Italian epidemic and later worldwide. More recently, the VOC 202012/01 variant (B.1.1.7) emerged and became highly prevalent in the UK, while other extensively mutated variants were identified in South Africa (B.1.351-501.V2), Nigeria and Brazil (B.1.128.P1). These variants may impact the clinical course of the disease with greater pathogenicity or challenge public health prophylactic measures as a result of increased transmissibility. Moreover, some variants may have the ability to escape currently used diagnostic tests or the host immune defenses, causing reinfections. For these reasons, the role played by stochastic (genetic drift-founder effect) or deterministic forces (selective pressure due to cross-immunity) in driving the evolution of the virus variants must be investigated to clarify the possible contribution of the vaccines to select escape variants. The general goal of this proposal is the study of the genomic epidemiology of SARS-CoV-2 in Italy, by sequencing a large number of viral genomes (at least 200 new genomes per month) collected in different regions of Italy. This will be possible by taking advantage of the participation of the project partners to an existing network named SCIRE (SARS-CoV-2 Italian Research Enterprise) including more than 70 centers all over the country. The study population will include COVID-19 symptomatic patients at different stages of the infection, asymptomatic subjects enrolled in screenings, and special populations such as immunocompromised patients and vaccinated subjects. The project will contribute to elucidate the clinical and public health impact of both already known and potentially new emerging SARS-CoV-2 strains circulating in Italy, in accordance with the indications of the international agencies. Importantly, the infrastructure built by the project will be a foundation for responding to possible future pandemics or re-emerging viruses. The consortium will be an appealing resource for international collaborations in the area of molecular epidemiology, facilitating the joint application to competitive EU research programs or attracting the interest of pharmaceutical companies, which in turn greatly reinforces the long-term sustainability of the network.