Emergence and outcomes of the SARS-CoV-2 ‘Marseille-4’ variant

https://doi.org/10.1016/j.ijid.2021.03.068Get rights and content
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Highlights

  • The severe acute respiratory syndrome (SARS-CoV-2) Marseille-4 variant caused an epidemic that started in August and is still ongoing.

  • This variant harbours 13 hallmark mutations, including one in the spike receptor binding domain.

  • The variant predominated in Marseille from September 2020 and caused a re-infection in 11 patients.

  • Hypoxemia was more frequent than with clade 20A strains that circulated before May 2020.

  • The sudden appearance of Marseille-4 points towards an animal reservoir, possibly mink.

Abstract

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.

Keywords

SARS-CoV-2
COVID-19
Variant
Marseille-4
Mutations
Spike
Molecular epidemiology

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