Role of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic.

The SARS-CoV-2 pandemic and large-scale genomic surveillance provided an exceptional opportunity to analyze mutations that appeared over three years in viral genomes. Here we studied mutations and their epidemic consequences for SARS-CoV-2 genomes from our center. We analyzed 61,397 SARS-CoV-2 genomes we sequenced from respiratory samples for genomic surveillance. Mutations frequencies were calculated using Nextclade, Microsoft Excel, and an in-house Python script. A total of 22,225 nucleotide mutations were identified, 220 (1.0%) being each at the root of ≥836 genomes, classifying mutations as 'hyperfertile'. Two seeded the European pandemic: P323L in RNA polymerase, associated with an increased mutation rate, and D614G in spike that improved fitness. Most 'hyperfertile' mutations occurred in areas not predicted with increased virulence. Their mean number was 8±6 (0-22) per 1,000 nucleotides per gene. They were 3.7-times more frequent in accessory than informational genes (13.9 versus 3.7/1,000 nucleotides). Particularly, they were 4.1-times more frequent in ORF8 than in the RNA polymerase gene. Interestingly, stop codons were present in 97 positions, almost only in accessory genes, including ORF8 (21/100 codons). most 'hyperfertile' mutations did not predict emergence of a new epidemic, and some were stop codons indicating the existence of so-named 'non-virulence' genes.

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Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Declaration of Competing Interest D.R. declares grants or contracts and royalties or licenses from Hitachi High-Technologies Corporation, Tokyo, Japan. He is a scientific board member of Eurofins company, and a founder and shareholder of a microbial culture company (Culture Top), two biotechnology companies (Techno-Jouvence, and Gene and Green TK), and an infectious diseases rapid diagnosis company (Pocramé). The other authors have no conflicts of interest to declare relative to the present study. Funding sources played no role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, and the preparation, review, or approval of the manuscript.