Emergence and outcome of the SARS-CoV-2 "Marseille-4" variant.

Introduction In Marseille, France, following a first SARS-CoV-2 outbreak in March-May 2020, a second epidemic phase occurred from June, involving ten new variants. The Marseille-4 variant caused an epidemic that started in August and is still ongoing. Materials and methods The 1,038 SARS-CoV-2 whole genome sequences obtained in our laboratory by next-generation sequencing with Illumina technology were analyzed using Nextclade and nextstrain/ncov pipelines and IQ-TREE. A Marseille-4-specific qPCR assay was implemented. Demographic and clinical features were compared between patients with Marseille-4 and earlier strains. Results Marseille-4 harbors 13 hallmark mutations. One leads to S477 N substitution in the spike receptor binding domain targeted by current vaccines. Using a specific qPCR, we observed that Marseille-4 caused 12-100% of SARS-CoV-2 infections in Marseille from September 2020, being involved in 2,106 diagnoses. This variant was more frequently associated with hypoxemia than clade 20A strains before May 2020. It caused re-infection in eleven patients SARS-CoV-2-diagnosed with different strains before June 2020, suggesting either short-term protective immunity or lack of cross-immunity. Discussion/conclusion Marseille-4 should be considered as a major SARS-CoV-2 variant. Its sudden appearance points toward an animal reservoir, possibly minks. The protective role of past-exposure and current vaccines against this variant should be evaluated.