AN IMPROVED GENOMIC SURVEILLANCE APPROACH TO DISSECT THE SARS-COV-2 PANDEMIC

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the only approach to rapidly monitor and tackle emerging variants of concern (VOC) of the COVID-19 pandemic. Such scrutiny is crucial to limit the spread of VOC that might escape the immune protection conferred by vaccination strategies. It is also becoming clear now that efficient genomic surveillance would require monitoring the host gene expression to identify prognostic biomarkers of efficacy and disease progression. Here we applied an integrated workflow for RNA extracted from nasal swabs to obtain in parallel the entire genome of SARS-CoV-2 and host respiratory epithelium transcriptome, representing the majority of Italian processed genomic samples. In addition, we have matured and applied novel proof-of-principle approaches to prioritize possible gain-of-function mutations by leveraging patients' metadata and isolated patient-specific signatures of SARS-CoV-2 infection. The goals mentioned above have all been achieved in a cost-effective manner that does not require automation, in an effort to allow any lab with a benchtop sequencer and a limited budget to perform integrated genomic surveillance on premises.