BACKGROUND: In Marseille, France, following a first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in March-May 2020, a second epidemic phase occurred from June, involving 10 new variants . The Marseille-4 variant caused an epidemic that started in August and is still ongoing .
METHODS: The 1038 SARS-CoV-2 whole genome sequences obtained in our laboratory by next-generation sequencing with Illumina technology were analysed 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 the Marseille-4 variant and those with earlier strains .
RESULTS: Marseille-4 harbours 13 hallmark mutations . One leads to an S477N substitution in the receptor binding domain of the spike protein targeted by current vaccines . Using a specific qPCR, it was observed that Marseille-4 caused 12-100% of SARS-CoV-2 infections in Marseille from September 2020, being involved in 2106 diagnoses . This variant was more frequently associated with hypoxemia than were clade 20A strains before May 2020 . It caused a re-infection in 11 patients diagnosed with different SARS-CoV-2 strains before June 2020, suggesting either short-term protective immunity or a lack of cross-immunity .
CONCLUSIONS: Marseille-4 should be considered as a major SARS-CoV-2 variant . Its sudden appearance points towards an animal reservoir, possibly mink . The protective role of past exposure and current vaccines against this variant should be evaluated.