Introduction: SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade.
Methods: Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra.
Results: In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon.
Discussion: We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.
Keywords: COVID-19; clade-discordant residues; ultra-deep sequencing; variant of concern; viral emergence; viral quasispecies.
Copyright © 2024 Martínez-González, Soria, Mínguez, Lorenzo-Redondo, Salar-Vidal, López-García, Esteban-Muñoz, Durán-Pastor, Somovilla, García-Crespo, de Ávila, Gómez, Esteban, Fernández-Roblas, Gadea, Domingo and Perales.