Whole-Genome Analysis of Various SARS-CoV-2 Clinical Isolates Establishes a Direct Positive Correlation between the Viral Load and Rate of Mutations

<b>Abstract</b><b>Objective</b> SARS-CoV-2 was first identified in China in late December 2019. To investigate its specific genomic features, whole and near-complete SARS-CoV-2 genome sequences were analyzed. <b>Methods</b> Clinical samples were collected from 18 COVID-19–positive patients and subjected to nucleic acid purification. Cell culturing was performed to extract various SARS-CoV-2 isolates. Whole-genome analysis was performed using next-generation sequencing, and phylogenetic analyses were conducted to determine genetic diversity of the various SARS-CoV-2 isolates. <b>Results</b> Thirty-two clinical samples were collected from 18 patients. The comparative analysis revealed molecular genetic evolutionary features and evolutionary dynamics of the entire genome. The next-generation sequencing data identified 8 protein-coding regions with 17 mutated proteins. The sequencing analysis identified largely invariant regions of SARS-CoV-2 genome along with 51 missense point mutations and deletions in 5¢ and 3¢ untranslated regions. The phylogenetic analysis revealed that V and GH are the dominant clades of SARS-CoV-2 circulating in the Gwangju region of South Korea. Moreover, statistical analysis confirmed a significant correlation between viral load (P &lt; 0.001) and mutation rate (P &lt; 0.0001) in 2 mutually exclusive SARS-CoV-2 clades. <b>Conclusion</b> Thus, we found novel nonsynonymous mutations throughout the whole genome of SARS-CoV-2. Furthermore, we successfully established a direct positive correlation between the viral copy number and the rate of mutations, which indicates frequent genomic alterations in SARS-CoV-2 in patients with high viral load. Our results provide an in-depth analysis of SARS-COV-2 whole genome which we believe, can point to an effective strategy for the development of vaccines and therapeutics for COVID-19.