It has been argued that vaccine-breakthrough infections of SARS-CoV-2 would likely accelerate the emergence of novel variants with immune evasion. This study explored the evolutionary patterns of the Delta variant in countries/regions with relatively high and low vaccine coverage based on large-scale sequences. Our results showed that (i) the sequences were grouped into two clusters (L and R); the R cluster was dominant, its proportion increased over time and was higher in the high-vaccine-coverage areas; (ii) genetic diversities in the countries/regions with low vaccine coverage were higher than those in the ones with high vaccine coverage; (iii) unique mutations and co-mutations were detected in different countries/regions; in particular, common co-mutations were exhibited in highly occurring frequencies in the areas with high vaccine coverage and presented in increasing frequencies over time in the areas with low vaccine coverage; (iv) five sites on the S protein were under strong positive selection in different countries/regions, with three in non-C to U sites (I95T, G142D and T950N), and the occurring frequencies of I95T in high vaccine coverage areas were higher, while G142D and T950N were potentially immune-pressure-selected sites; and (v) mutation at the N6-methyladenosine site 4 on ORF7a (C27527T, P45L) was detected and might be caused by immune pressure. Our study suggested that certain variation differences existed between countries/regions with high and low vaccine coverage, but they were not likely caused by host immune pressure. We inferred that no extra immune pressures on SARS-CoV-2 were generated with high vaccine coverage, and we suggest promoting and strengthening the uptake of the COVID-19 vaccine worldwide, especially in less developed areas.
Keywords: SARS-CoV-2; co-mutation; genetic divergence; immune pressure; methylation; vaccine coverage.