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

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 1 st and June 12 th 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 R e = 0.71, 95%CI: 0.64, 0.77) on April 1 st to having a 50% transmission advantage on June 12 th (relative R e = 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, 3 may be an early warning signal for Delta lineage expansion.