Systematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population I

Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of Spike in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets. Furthermore, we found that subvariants and putative quasi-species with alterations characteristic of future VOCs and/or predicted to be functionally important arose frequently, but always extinguished. Systematic screening of functionally relevant domains in pathogens could thus provide a powerful tool for monitoring spread and mutational trajectories, particularly those with zoonotic potential. Overall design: RNAseq and sequence variant analysis for 63036 human nasopharyngeal swabs for SARS-CoV-2, with 1928 negative swabs and 2886 synthetic controls. (part2) Additional RNAseq and sequence variant analysis for 3129 human nasopharyngeal swabs for SARS-CoV-2, with 283 negative swabs and 259 synthetic controls. Please note that the 'sparseq_sample_data_GEOver_v3.txt' and 'sparseq_sample_data_GEOver_part2_v3.txt' files were replaced with the 'sparseq_sample_data_GEOver_v4.txt' and 'sparseq_sample_data_GEOver_part2_v4.txt', respectively, on Oct 10, 2024 (only to fix some typos in text fields, no change to the number of samples). Please note that the records have been updated with 10 additional sample records and the updated 'sparseq_sample_data_GEOver_part2_v5.txt', 'sparseq_sample_data_GEOver_v5.txt'files on Nov 5, 2024.