COVID19 is a current pandemic disease due to the novel coronavirus SARS-CoV-2. The scientific community mounted a strong response by accelerating research and innovation, and rapidly setting the basis to the understanding of molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key step of SARS-CoV2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of structural and functional data on key actors of the replicatory machinery of SARS-CoV-2, filling the gaps in the current availability of structural data using homology modelling. Moreover, learning from similar viruses, we collect literature data to reconstruct the pattern of interactions among protein actors of the SARS-CoV-2 RNA polymerase machinery. In this pattern, an important role is played by co-factors, like Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors holding the entire machinery together to enhance the efficiency of RNA replication.

The study aims to evaluate the rate of readmission in patients affected by diabetic foot ulcers (DFUs), causes and the outcomes of patients requiring a new hospitalization. This study is a retrospective observational study including consecutive patients requiring hospitalization since January 2019 to September 2022 due to a DFU. Once they were discharged, patients were regularly followed as outpatients. After 6 months of follow-up, the rate of hospital readmission for a diabetic foot problem was recorded. According to the readmission or not, patients were divided in two groups, readmitted and not readmitted patients respectively. Hence, all patients were followed for six months more and outcomes for the two groups were analyzed and compared. The mean age was 6812yrs, with a prevalence of male (72.6%); the majority of patients were affected by type 2 diabetes (>90%) with a mean diabetes duration of approximately 20yrs. After 6 months of follow-up, 68 (21.9%) patients were readmitted. The main reason of hospital readmission were the presence of critical limb ischaemia (CLI) in the contralateral limb (6.1%), the recurrence of CLI in the previous treated limb (4.5%) and the onset of new infected DFU in the contralateral foot (4.5%). Readmitted patients reported lower rate of healing (51.5vs89.2%,p<0.0001) and higher rate of major amputation (10.3vs4.5%,p=0.04) in comparison to not readmitted patients. CLI and dialysis resulted independent predictors of hospital readmission. Hospital readmission is frequent issue among patients with DFUs, increasing the risk of non-healing and major amputation. CLI resulted the main cause of new hospitalization.