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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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| Authors: | Philippe Colson Philippe Gautret Jeremy Delerce Hervé Chaudet Pierre Pontarotti Patrick Forterre Raphael Tola Marielle Bedotto Léa Delorme Wahiba Bader Anthony Levasseur Jean-Christophe Lagier Matthieu Million Nouara Yahi Jacques Fantini Bernard La Scola Pierre-Edouard Fournier Didier Raoult |
| Institution: | 1. IHU Méditerranée Infection, Marseille, France;2. IHU Méditerranée Infection, Marseille, France
Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France Institut de Recherche pour le Développement (IRD), Vecteurs—Infections Tropicales et Méditerranéennes (VITROME), Aix-Marseille University, Marseille, France;3. IHU Méditerranée Infection, Marseille, France Institut de Recherche pour le Développement (IRD), Vecteurs—Infections Tropicales et Méditerranéennes (VITROME), Aix-Marseille University, Marseille, France French Armed Forces Center for Epidemiology and Public Health (CESPA), Camp de Sainte Marthe, Marseille, France;4. IHU Méditerranée Infection, Marseille, France Centre national de la recherche scientifique (CNRS), Marseille, France;5. Département de Microbiologie, Institut Pasteur, Paris, France Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France;6. IHU Méditerranée Infection, Marseille, France Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France;7. IHU Méditerranée Infection, Marseille, France Institut de Recherche pour le Développement (IRD), Microbes Evolution Phylogeny and Infections (MEPHI), Aix-Marseille University, Marseille, France;8. IHU Méditerranée Infection, Marseille, France Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France Institut de Recherche pour le Développement (IRD), Microbes Evolution Phylogeny and Infections (MEPHI), Aix-Marseille University, Marseille, France;9. INSERM UMR_S 1072, Aix-Marseille Université, Marseille, France |
| 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. |
| Keywords: | epidemic Marseille-4 ORF8 Pangolin B 1 1 160 SARS-CoV-2 variants |