Continuous mutation of SARS-CoV-2 during migration via three routes at the beginning of the pandemic.

Background: It remains unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection started, spread worldwide, and mutated to result in the present variants. This difficulty can be attributed to the limitations associated with the analytical methodology for presenting the differences among genomic sequences. In this study, we critically analysed the early data to explain the start and spread of the pandemic. Methods: Objective analyses of the RNA sequences of earlier variants of SARS-CoV-2 (up to September 1, 2020, available in DDBJ and GISAID) were performed using Principal Component Analysis (PCA). The results were compared with information on the collection dates and location. The PCA was also conducted for 12 variants of interest to the WHO as of September 2021, and compared with earlier data. Results: The pandemic began in Wuhan, China. This strain was suspected to be related to other reported animal viruses; however, they had a minimal similarity. The strain then spreads via three routes while accumulating mutations. Several viral subgroups were identified along the routes, each with a large number of patients reported, indicating high infectivity to humans. These routes were only confirmed by the early data analysis, because newer variants would have more mutations, and would be preferentially be examined by PCA if they were included. On the original axes found in the early variants, the newer variants revealed that they retained previously acquired mutations, which helped to reveal the viral ancestors of the newer variants. The rate of mutation was found to be comparable to that of the influenza H1N1 virus, which causes recurrent seasonal epidemics. Another threat imposed by SARS-CoV-2 is that if the pandemic cannot be contained, new variants may emerge annually, preventing herd immunity.