First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France

Abstract

The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here, we describe the first cases diagnosed with this variant in south-eastern France. We identified 13 cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travelers returning from Tanzania. Overall, viral genomes displayed a mean (±standard deviation) number of 65.9 ± 2.5 (range, 61-69) nucleotide substitutions and 31.0 ± 8.3 (27-50) nucleotide deletions, resulting in 49.6 ± 2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4 ± 1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions highlighted a significant enlargement and flattening of the surface of the 21L/BA.2 N-terminal domain of the spike protein compared to that of the 21K/BA.1 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country, and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.

Keywords: Omicron; SARS-CoV-2; emergence; southern France; travel; variant.

Figure 1

Map of the Omicron 21L/BA.2 spike protein with signature amino acid substitutions and deletions (A) and structural features of 21L/BA.2 Omicron variant spike protein (B). (A) Amino acid substitutions and deletions shared with the 21K/BA.1 Omicron variant are indicated by a red font. Amino acid substitutions and deletions shared with the 21M/BA.3 Omicron variant are underlined. See also Table 1B. (B) Structural model of the Omicron 21L/BA.2 spike protein with mutations highlighted in red atomic spheres (left panel) or in electrostatic surface rendering (right panel). Note the flat surface of the N‐terminal domain that faces lipid rafts of the host cell membrane. The S1–S2 cleavage site is indicated by an arrow. The color scale for the electrostatic surface potential (negative in red, positive in blue, neutral in white) is indicated. NTD, N‐terminal domain; RBD, receptor‐binding domain

Figure 2

Phylogeny reconstruction based on genomes of the 21L/BA.2 Omicron variant were obtained in the present study. (A) incorporated genome sequences of 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants. (B) is a zoom of the 21L/BA.2 Omicron cluster of (A). Phylogenetic tree was built using the nextstrain/ncov tool (https://github.com/nextstrain/ncov) then visualized with Auspice (https://docs.nextstrain.org/projects/auspice/en/stable/). X‐axis shows time. The 21L/BA.2 Omicron genomes the closest genetically to those obtained in our institute were selected using the Usher tool (https://genome.ucsc.edu/cgi-bin/hgPhyloPlace) and the GISAID BLAST tool (https://www.epicov.org/epi3/) and they were incorporated in the phylogenetic analysis in addition to all 21L/BA.2 Omicron variant genomes from France are available in GISAID as of 02/02/2022. Sequences obtained in our laboratory (IHU Méditerranée Infection) are indicated by a dark blue arrow and their GISAID identifier is indicated. Countries are indicated when they are not France. Gisaid hcov‐19 acknowledgment table is provided as supplementary file.

Figure 3

Number of genomes of the SARS‐CoV‐2 21L/BA.2 Omicron variant available in GISAID and chronology of collections of respiratory samples from where they were obtained. (A) Number of genomes of the SARS‐CoV‐2 21L/BA.2 Omicron variant are available in the GISAID sequence database (https://www.gisaid.org/) as of 02/02/2022. (B) Chronology of SARS‐CoV‐2 diagnoses with the 21L/BA.2 Omicron variant for genomes were deposited in the GISAID sequence database and obtained worldwide. (C) Chronology of SARS‐CoV‐2 diagnoses with the 21L/BA.2 Omicron variant for genomes deposited in the GISAID sequence database and obtained in France or in our university hospital institute. The number of genomes was analyzed until 02/02/2022. Total number of genomes analyzed was 36 428. A total of 1093 genomes were excluded as the date of sample collection was uncomplete (days or months were lacking)