The following is a summary of “Use of Whole-Genome Sequencing to Estimate the Contribution of Immune Evasion and Waning Immunity on Decreasing COVID-19 Vaccine Effectiveness,” published in March 2023 issue of Infectious Diseases by Lind, et al.

Uncertainty exists regarding how falling coronavirus disease 2019 (COVID-19) vaccine efficacy (VE) is influenced by variant-specific immune evasion and fading protection. Therefore, using the help of whole-genome sequencing (WGS), researchers sought to determine the impact of variant-specific immune evasion and waning protection on the declining effectiveness of COVID-19 vaccines following the emergence of the Delta variant. 

They conducted a test-negative case-control study among people tested for SARS-CoV-2 between 1 April and 24 August 2021, using whole-genome sequencing (WGS) and calendar-period-based classification to classify the variants. 

The study included 2,029 cases (positive, sequenced samples) and 343,727 controls (negative tests). The results showed that the vaccine effectiveness (VE) 14-89 days after the second dose was significantly higher against the Alpha variant (84.4%; 95% CI, 75.6%-90.0%) compared to the Delta variant (68.9%; 95% CI, 58.0%-77.1%). In addition, the odds of Delta infection were significantly higher 90-149 days after the second dose than 14-89 days after the second dose (P value = .003). The VE estimates based on calendar-period classification closely approximated the WGS-classified estimates. However, the calendar-period-based classification was subject to misclassification, with 35% of Alpha and 4% of Delta variants being misclassified.

The study suggested that waning protection and variant-specific immune evasion contributed to the lower effectiveness of COVID-19 vaccines against the Delta variant. In addition, the results highlighted the need for WGS when multiple variants were circulating to avoid misclassification of variants, which could impact VE estimates.

Reference: academic.oup.com/jid/article/227/5/663/6835054