Repeated emergence of probabilistically and chronologically anomalous mutations in SARS-CoV-2 during the COVID-19 pandemic

Mutations in 22 major SARS-CoV-2 variants before June 2023 are investigated. It is found that mutation spectra of spike (surface glycoprotein) in Alpha and Delta variants are deviant from the normal human SARS-CoV-2 mutation spectrum with statistical significance. Sudden surges of G614D mutation, a reversion of the earliest and the most dominant point mutation in SARS-CoV-2, are observed in the non-early periods of Delta and Omicron BA.2 prevalence, which does not agree with the expectation of natural evolution. Outstanding number of unique pure reversion mutants consisting only of reverse mutations are observed in the beginning of Omicron BA.1 prevalence, many of which can emerge only through a large amount of recombination. Community spread can hardly cause these probabilistically and chronologically anomalous mutation patterns.