Low-cost method for finding new coronavirus variants

Since the onset of the pandemic, thousands of viral genomes have been sequenced to reconstruct the evolution and global spread of the coronavirus. This is important for the identification of particularly concerning variants that are more contagious, pathogenic, or resistant to the existing vaccines.

For global surveillance of the SARS-CoV-2 genome, it is crucial to sequence and analyse many samples in a cost-effective way. Therefore, researchers in the Bienko-Crosetto laboratory at Karolinska Institutet and Science for Life Laboratory (SciLifeLab) in Sweden have developed a new method, named COVseq, that can be used for surveillance of the viral genome on a massive scale at a low cost.

First, many copies of the viral genome are created using so-called multiplex PCR (polymerase chain reaction). The samples are then labelled and pooled together in the same sequencing library, using a previous method developed in the Bienko-Crosetto laboratory and now adapted for SARS-CoV-2 analysis.

”By performing reactions in very small volumes and pooling together hundreds of samples into the same sequencing library, we can sequence potentially thousands of viral genomes per week at a cost of less than 15 dollars per sample,” says Ning Zhang, who previously worked as a postdoctoral researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet and is co-first author together with PhD students Michele Simonetti and Luuk Harbers active at the same department.

Comparative analyses of 29 SARS-CoV-2 positive samples revealed that COVseq had a similar ability as the standard method to identify small changes in the genome. Analyses of 245 additional samples showed that COVseq also had a high ability to detect emergent coronavirus variants of potential concern. The key advantage of COVseq over existing methods is cost-effectiveness.

”Our inexpensive method could immediately be used for SARS-CoV-2 genomic surveillance by public health agencies and could also be easily adapted to other RNA viruses, such as influenza and dengue viruses,” says Nicola Crosetto, senior researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and last author of the paper.

The study was done in collaboration with researchers at the 'Amedeo di Savoia' Hospital and the Candiolo Cancer Institute in Turin, Italy. The research was supported by grants from the SciLifeLab National COVID-19 Research Program, financed by the Knut and Alice Wallenberg Foundation, and grants from the Swedish Foundation for Strategic Research, as well as private donations from Chiesi Pharma AB and the Tetra Laval Group. The authors declare no competing interests.

Publication: ”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. Nature Communications, online 23 June 2021, doi: 10.1038/s41467-021-24078-9.

For more information, please contact: Nicola Crosetto, MD, PhD The Bienko-Crosetto Laboratory for Quantitative Genome Biology Science for Life Laboratory Department of Medical Biochemistry and Biophysics, Karolinska Institutet E-mail: nicola.crosetto@ki.se Phone: +46 73 986 53 79