This study analyzed 220 SARS-CoV-2 genomic sequences from December 2019 to March 2020 to investigate viral mutations. Researchers identified eight novel recurrent mutation hotspots, finding different patterns in European and North American strains. A key mutation in the RNA-dependent-RNA polymerase (RdRp) gene, at position 14408, emerged in Italy in February 2020. Viruses with this RdRp mutation had a significantly higher number of point mutations (a median of 3 versus 1). This finding is critical as RdRp is a primary target for antiviral drugs, and this mutation's proximity to a predicted drug-binding site warrants investigation for potential drug resistance.