The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule.

Abstract

The nature and dynamics of mutations associated with the emergence, spread, and vanishing of SARS‐CoV‐2 variants causing successive waves are complex. We determined the kinetics of the most common French variant (“Marseille‐4”) for 10 months since its onset in July 2020. Here, we analyzed and classified into subvariants and lineages 7453 genomes obtained by next‐generation sequencing. We identified two subvariants, Marseille‐4A, which contains 22 different lineages of at least 50 genomes, and Marseille‐4B. Their average lifetime was 4.1 ± 1.4 months, during which 4.1 ± 2.6 mutations accumulated. Growth rate was 0.079 ± 0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell‐shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille‐4B emerged when the other Marseille‐4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS‐CoV‐2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.