Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples

Orsolya Anna Pipek, Anna Medgyes-Horváth*, VEO Technical Working Group, József Stéger, Krisztián Papp, Dávid Visontai, Marion Koopmans, David Nieuwenhuijse, Bas B. Oude Munnink, Guy Cochrane, Nadim Rahman, Carla Cummins, David Yu Yuan, Sandeep Selvakumar, Milena Mansurova, Colman O’Cathail, Alexey Sokolov, Ross Thorne, Nathalie Worp, Clara AmidIstván Csabai

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Systematic monitoring of SARS-CoV-2 co-infections between different lineages and assessing the risk of intra-host recombinant emergence are crucial for forecasting viral evolution. Here we present a comprehensive analysis of more than 2 million SARS-CoV-2 raw read datasets submitted to the European COVID-19 Data Portal to identify co-infections and intra-host recombination. Co-infection was observed in 0.35% of the investigated cases. Two independent procedures were implemented to detect intra-host recombination. We show that sensitivity is predominantly determined by the density of lineage-defining mutations along the genome, thus we used an expanded list of mutually exclusive defining mutations of specific variant combinations to increase statistical power. We call attention to multiple challenges rendering recombinant detection difficult and provide guidelines for the reduction of false positives arising from chimeric sequences produced during PCR amplification. Additionally, we identify three recombination hotspots of Delta – Omicron BA.1 intra-host recombinants.

Original languageEnglish
Article number517
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 15 Jan 2024

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Publisher Copyright: © 2024, The Author(s).

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