Inflection in prevalence of SARS-CoV-2 infections missing the N501Y mutation as a marker of rapid Delta (B.1.617.2) lineage expansion in Ontario, Canada

Brown, K. A.; Gubbay, J.; Buchan, S. A.; Daneman, N.; Mishra, S.; Patel, S.; Day, T.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta lineage (B.1.617.2) was implicated in the SARS-CoV-2 surge in India. We sought to describe the rapid expansion of the Delta lineage in Ontario, Canada (population 15 million) using mutation profile information and confirmatory whole genome sequencing. Methods: All laboratory-confirmed SARS-CoV-2 cases reported to Public Health Ontario between April 1st and June 12th 2021, with cycle threshold values <=35, were eligible for screening for the N501Y and the E484K mutations. We classified cases via mutation screening as: (1) N501Y-/E484K- (wild-type/Delta), (2) Alpha (N501Y+/E484K-), (3) Beta/Gamma (N501Y+/E484K+), or (4) N501Y-/E484K+ (predominantly B.1.525, and B.1.1.318). Results: The N501Y-/E484K- mutation profile went from having a 29% transmission deficit relative to Alpha (relative Re = 0.71, 95%CI: 0.64, 0.77) on April 1st to having a 50% transmission advantage on June 12th (relative Re = 1.50, 95%CI: 1.31, 1.71). Whole genome sequencing of N501Y-/E484K- cases (N=583) confirmed that the pattern of increasing relative reproduction number coincided with the replacement of wild-type with Delta variant (from 2.2% in early April, to 83% in late May). Discussion: Delta is rapidly overtaking other SARS-CoV-2 variants in Ontario, and has a substantial transmission advantage. An inflection in the proportion of cases missing the N501Y mutation from rapidly decreasing to rapidly increasing, may be an early warning signal for Delta lineage expansion.