A genetic barcode of SARS-CoV-2 for monitoring global distribution of different clades during the COVID-19 pandemic

Abstract

Objective: The SARS-CoV-2 pathogen has established endemicity in humans. This necessitates the development of rapid genetic surveillance methodologies to serve as an adjunct to existing comprehensive, albeit though slower, genome sequencing-driven approaches. Methods: A total of 21,789 complete genomes were downloaded from GISAID on May 28, 2020, for analyses. We have defined the major clades and subclades of circulating SARS-CoV-2 genomes. A rapid sequencing-based genotyping protocol was developed and tested on SARS-CoV-2-positive RNA samples by next-generation sequencing. Results: We describe eleven major mutation events that defined five major clades (G614, S84, V251, I378, and D392) of globally-circulating viral populations. The clades can be specifically identified using an 11-nucleotide genetic barcode. An analysis of amino acid variation in SARS-CoV-2 proteins provided evidence of substitution events in the viral proteins involved in both host entry and genome replication. Conclusion: Globally-circulating SARS-CoV-2 genomes could be classified into five major clades based on mutational profiles defined by an 11-nucleotide barcode. We have successfully developed a multiplexed sequencing-based, rapid genotyping protocol for high-throughput classification of major clade types of SARS-CoV-2 in clinical samples. This barcoding strategy will be required to monitor genetic diversity decrease as treatment and vaccine approaches become widely available.