COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance

Michele Simonetti, Ning Zhang, Luuk Harbers, Maria Grazia Milia, Silvia Brossa, Thi Thu Huong Nguyen, Francesco Cerutti, Enrico Berrino, Anna Sapino, Magda Bienko, Antonino Sottile, Valeria Ghisetti () and Nicola Crosetto ()
Additional contact information
Michele Simonetti: Karolinska Institutet
Ning Zhang: Karolinska Institutet
Luuk Harbers: Karolinska Institutet
Maria Grazia Milia: Ospedale ‘Amedeo di Savoia’
Silvia Brossa: Instituto di Candiolo FPO—IRCCS, Candiolo
Thi Thu Huong Nguyen: Karolinska Institutet
Francesco Cerutti: Ospedale ‘Amedeo di Savoia’
Enrico Berrino: Instituto di Candiolo FPO—IRCCS, Candiolo
Anna Sapino: Instituto di Candiolo FPO—IRCCS, Candiolo
Magda Bienko: Karolinska Institutet
Antonino Sottile: Instituto di Candiolo FPO—IRCCS, Candiolo
Valeria Ghisetti: Ospedale ‘Amedeo di Savoia’
Nicola Crosetto: Karolinska Institutet

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract While mass-scale vaccination campaigns are ongoing worldwide, genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the emergence and global spread of viral variants of concern (VOC). Here, we present a streamlined workflow—COVseq—which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We benchmark COVseq against a standard library preparation method (NEBNext) on 29 SARS-CoV-2 positive samples, reaching 95.4% of concordance between single-nucleotide variants detected by both methods. Application of COVseq to 245 additional SARS-CoV-2 positive samples demonstrates the ability of the method to reliably detect emergent VOC as well as its compatibility with downstream phylogenetic analyses. A cost analysis shows that COVseq could be used to sequence thousands of samples at less than 15 USD per sample, including library preparation and sequencing costs. We conclude that COVseq is a versatile and scalable method that is immediately applicable for SARS-CoV-2 genomic surveillance and easily adaptable to other pathogens such as influenza viruses.

Date: 2021
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DOI: 10.1038/s41467-021-24078-9

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