Analysis of SARS-CoV-2 Variants From 24,181 Patients Exemplifies the Role of Globalization and Zoonosis in Pandemics

Abstract

After the end of the first epidemic episode of SARS-CoV-2 infections, as cases began to rise again during the summer of 2020, we at IHU Méditerranée Infection in Marseille, France, intensified the genomic surveillance of SARS-CoV-2, and described the first viral variants. In this study, we compared the incidence curves of SARS-CoV-2-associated deaths in different countries and reported the classification of SARS-CoV-2 variants detected in our institute, as well as the kinetics and sources of the infections. We used mortality collected from a COVID-19 data repository for 221 countries. Viral variants were defined based on ≥5 hallmark mutations along the whole genome shared by ≥30 genomes. SARS-CoV-2 genotype was determined for 24,181 patients using next-generation genome and gene sequencing (in 47 and 11% of cases, respectively) or variant-specific qPCR (in 42% of cases). Sixteen variants were identified by analyzing viral genomes from 9,788 SARS-CoV-2-diagnosed patients. Our data show that since the first SARS-CoV-2 epidemic episode in Marseille, importation through travel from abroad was documented for seven of the new variants. In addition, for the B.1.160 variant of Pangolin classification (a.k.a. Marseille-4), we suspect transmission from farm minks. In conclusion, we observed that the successive epidemic peaks of SARS-CoV-2 infections are not linked to rebounds of viral genotypes that are already present but to newly introduced variants. We thus suggest that border control is the best mean of combating this type of introduction, and that intensive control of mink farms is also necessary to prevent the emergence of new variants generated in this animal reservoir.

Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein

“…Overall, these observations show once again the unpredictability of the emergence of new SARS-CoV-2 variants and their possible introduction from abroad, and they exemplify the difficulty in controlling such introductions and subsequent spread. They also confirm the value of the SARS-CoV-2 genomic surveillance that we started at the very beginning of the pandemic in the Marseille geographical area as soon as we diagnosed the first SARS-CoV-2 infection [19] and that we expanded during the summer of 2020 [2,3]. Such surveillance program was implemented at the national level in 2021 through the French Emergen consortium (https:// www.…”

“…In addition, 25 nucleotide substitutions and 33 nucleotide deletions located elsewhere in the genome differ between the two genotypes. The pattern of mutations therefore indicates that the sequences determined in this study represent a new variant, which we have named "IHU" (in reference to our institute), based on our previous definition [3]. A phylogenetic analysis performed using the nextstrain/ncov tool (https:// github.…”

“…SARS-CoV-2 emerged in China in December 2019 and was declared a pandemic 21 months ago [1]. We have shown since the summer of 2020 that several SARS-CoV-2 variants have emerged in southeastern France and have caused distinct epidemics, either successive or superimposed [2,3]. We also reported that these variants were often introduced from abroad but could also be mink.…”

“…In addition, codon 27 of the ORF8 gene is changed to a stop codon, as in the Alpha variant [14]. Some members of the Marseille-4 variant lineage (B.1.160), which predominated in the Marseille geographical area between August 2020 and February 2021 [3], also exhibit a stop codon in the ORF8 gene, but at another position.…”

Culture and identification of a “Deltamicron” SARS-CoV-2 in a three cases cluster in southern France

“…This period spanned between December 27 th , 2021 and February 14 th , 2022 in our geographical area, as assessed by our SARS-CoV-2 genotypic surveillance based on variant-specific qPCR and next-generation genomic sequencing. 3,28,29 In January 2022, genomes harboring mutations from both Delta and Omicron 21K/BA.1 variants were reported in Cyprus but it was questioned whether sequences might have resulted from contamination. 23 Still, 15 genomes as of 27/02/2022 being hybrids of these two variants and highly similar between each other were reported since February 2022 (https://github.com/cov-lineages/pango-designation/issues/444).…”