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      Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation in France

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          Abstract

          From December 2021-February 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and developed an unbiased bioinformatics method for the detection of co-infections involving genetically distinct SARS-CoV-2 lineages. Applied on 21,387 samples collected between December 6, 2021 to February 27, 2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Among the 53 co-infected patients, a total of 21 patients (39.6%) were not vaccinated. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants.

          Abstract

          Monitoring of co-infections of SARS-CoV-2 variants is important to evaluate their clinical impact and the risk of emergence of recombinants. Here, the authors develop and validate a methodological pipeline to detect co-infections and apply it to samples from France in early 2022, when Delta and Omicron were co-circulating.

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          Most cited references18

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          Cutadapt removes adapter sequences from high-throughput sequencing reads

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            Minimap2: pairwise alignment for nucleotide sequences

            Heng Li (2018)
            Recent advances in sequencing technologies promise ultra-long reads of ∼100 kb in average, full-length mRNA or cDNA reads in high throughput and genomic contigs over 100 Mb in length. Existing alignment programs are unable or inefficient to process such data at scale, which presses for the development of new alignment algorithms.
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              Twelve years of SAMtools and BCFtools

              Abstract Background SAMtools and BCFtools are widely used programs for processing and analysing high-throughput sequencing data. They include tools for file format conversion and manipulation, sorting, querying, statistics, variant calling, and effect analysis amongst other methods. Findings The first version appeared online 12 years ago and has been maintained and further developed ever since, with many new features and improvements added over the years. The SAMtools and BCFtools packages represent a unique collection of tools that have been used in numerous other software projects and countless genomic pipelines. Conclusion Both SAMtools and BCFtools are freely available on GitHub under the permissive MIT licence, free for both non-commercial and commercial use. Both packages have been installed >1 million times via Bioconda. The source code and documentation are available from https://www.htslib.org.
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                Author and article information

                Contributors
                laurence.josset@chu-lyon.fr
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                23 October 2022
                23 October 2022
                2022
                : 13
                : 6316
                Affiliations
                [1 ]GRID grid.413852.9, ISNI 0000 0001 2163 3825, Laboratoire de Virologie, Institut des Agents Infectieux, Laboratoire associé au Centre National de Référence des virus des infections respiratoires, , Hospices Civils de Lyon, ; F-69004 Lyon, France
                [2 ]GRID grid.413852.9, ISNI 0000 0001 2163 3825, GenEPII sequencing platform, Institut des Agents Infectieux, , Hospices Civils de Lyon, ; F-69004 Lyon, France
                [3 ]GRID grid.25697.3f, ISNI 0000 0001 2172 4233, CIRI, Centre International de Recherche en Infectiologie, Team VirPath, , Univ Lyon, Inserm,U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ; ENS de Lyon, F-69007 Lyon, France
                Author information
                http://orcid.org/0000-0002-0261-2495
                http://orcid.org/0000-0002-8959-2123
                Article
                33910
                10.1038/s41467-022-33910-9
                9588762
                36274062
                67d54dd7-e86c-4338-bcf9-15937ac4ac57
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 March 2022
                : 7 October 2022
                Funding
                Funded by: Santé publique France, the French national public health agency. Caisse nationale d’assurance maladie (Cnam), the national health insurance funds. “Enhancing Whole Genome Sequencing (WGS) and/or Reverse Transcription Polymerase Chain Reaction (RT-PCR) national infrastructures and capacities to respond to the COVID-19 pandemic in the European Union and European Economic Area” (Grant Agreement ECDC/HERA/2021/007 ECDC. 12221).
                Categories
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                © The Author(s) 2022

                Uncategorized
                sars-cov-2,viral infection,epidemiology,genome informatics
                Uncategorized
                sars-cov-2, viral infection, epidemiology, genome informatics

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