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

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Colson, Philippe | Gautret, Philippe | Delerce, Jeremy | Chaudet, Hervé | Pontarotti, Pierre | Forterre, Patrick | Tola, Raphael | Bedotto, Marielle | Delorme, Léa | Bader, Wahiba | Levasseur, Anthony | Lagier, Jean‐christophe | Million, Matthieu | Yahi, Nouara | Fantini, Jacques | La Scola, Bernard | Fournier, Pierre‐edouard | Raoult, Didier

Edité par CCSD ; Wiley-Blackwell -

International audience. 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.

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