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

Marie-Ming Aynaud, Lauren Caldwell, Khalid N. Al-Zahrani, Seda Barutcu, Kin Chan, Andreea Obersterescu, Abiodun A. Ogunjimi, Min Jin, Kathleen-Rose Zakoor, Shyam Patel, Ron Padilla, Mark C. C. Jen, Princess Mae Veniegas, Nursrin Dewsi, Filiam Yonathan, Lucy Zhang, Amelia Ayson-Fortunato, Analiza Aquino, Paul Krzyzanowski, Jared Simpson, John Bartlett, Ilinca Lungu, Bradly G. Wouters, James M. Rini, Michael Gekas, Susan Poutanen, Laurence Pelletier, Tony Mazzulli and Jeffrey L. Wrana ()
Additional contact information
Marie-Ming Aynaud: Toronto
Lauren Caldwell: Toronto
Khalid N. Al-Zahrani: Toronto
Seda Barutcu: Toronto
Kin Chan: Toronto
Andreea Obersterescu: Toronto
Abiodun A. Ogunjimi: Toronto
Min Jin: Toronto
Kathleen-Rose Zakoor: Toronto
Shyam Patel: Toronto
Ron Padilla: Toronto
Mark C. C. Jen: Toronto
Princess Mae Veniegas: Toronto
Nursrin Dewsi: Toronto
Filiam Yonathan: Toronto
Lucy Zhang: Toronto
Amelia Ayson-Fortunato: Toronto
Analiza Aquino: Toronto
Paul Krzyzanowski: Toronto General Hospital
Jared Simpson: Toronto General Hospital
John Bartlett: Toronto General Hospital
Ilinca Lungu: Toronto General Hospital
Bradly G. Wouters: Toronto
James M. Rini: Toronto
Michael Gekas: Toronto
Susan Poutanen: Toronto
Laurence Pelletier: Toronto
Tony Mazzulli: Toronto
Jeffrey L. Wrana: Toronto

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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 here 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 the Spike gene in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets. Furthermore, we found that VOC mutant derivatives and putative quasispecies that targeted functionally important residues and were found in future VOCs arose frequently, but were 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.

Date: 2024
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DOI: 10.1038/s41467-024-55031-1

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