key: cord-0754422-9yr45hbc authors: Colson, P.; Delerce, J.; Beye, M.; LEVASSEUR, A.; Boschi, C.; Houhamdi, L.; Tissot-Dupont, H.; Yahi, N.; Million, M.; LA SCOLA, B.; Fantini, J.; Raoult, D.; Fournier, P.-E. title: First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France date: 2022-02-10 journal: nan DOI: 10.1101/2022.02.08.22270495 sha: 12c710adc5765d75ddfafdb24c04c8144bba9615 doc_id: 754422 cord_uid: 9yr45hbc 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 thirteen cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travellers 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 pointed out a significant enlargement and flattening of the 21L/BA.2 N-terminal domain surface compared with that of the 21K/BA.2 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. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 10, 2022. ; https://doi.org/10.1101/2022.02.08.22270495 doi: medRxiv preprint All 21L/BA.2 Omicron variant-positive respiratory samples exhibited the same 127 combination of spike mutations as screened by real-time qPCR: negativity for L452R, and, 128 when performed, positivity for K417N and P681H and negativity for E484K and P681R 129 (Table 1 ). In addition, the TaqPath COVID-19 kit (Thermo Fisher Scientific, Waltham, USA) 130 provided positive signals for all three genes targeted (ORF1, S, and N), except for one sample 131 that showed positivity for the N gene but negativity for both ORF1 and S genes, which was 132 most likely due to a low viral load (qPCR cycle threshold, 32). Thus, 21L/BA. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint obtained in our institute were part of three clusters. Two genomes that were retrieved from the 156 two patients who travelled in Tanzania were clustered with genomes obtained in England and 157 South Africa (Figure 2 ). The genome retrieved from the Dutch patient was clustered with two 158 genomes obtained in Nepal and Singapore. All other six genomes were most closely related to 159 genomes from France and Denmark. As the first two cases we diagnosed were most likely is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 10, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint commented on, and approved the final manuscript. 257 The dataset generated and analyzed during the current study are available in the GISAID 259 database (https://www.gisaid.org/). 260 This study has been approved by the ethics committee of University Hospital Institute (IHU) 262 Méditerranée Infection (N°2022-008). Access to the patients' biological and registry data 263 issued from the hospital information system was approved by the data protection committee is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 10, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 10, 2022. ; https://doi.org/10.1101/2022.02.08.22270495 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 10, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Untangling introductions and persistence in 271 COVID-19 resurgence in Europe Analysis of SARS-CoV-2 variants from 273 24,181 patients exemplifies the role of globalisation and zoonosis in pandemics The emergence, genomic diversity and global spread 276 of SARS-CoV-2 SARS-CoV-2 variants, spike mutations and 279 immune escape Where did Omicron come from? Three key theories CoVariants: SARS-CoV-2 mutations and variants of interest Omicron escapes the majority of existing SARS-CoV-2 France except IHU Méditerranée Infection IHU Méditerranée Infection Fig. 3