Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 227, Issue 5, Pages 663-674Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiac453
Keywords
COVID-19; vaccine effectiveness; variant-specific immune evasion; waning; whole-genome sequencing
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Using whole genome sequencing (WGS), the study provides evidence of declining vaccine effectiveness and variant-specific immune evasion during the Delta wave. The study suggests that calendar-period-based classification is prone to variant misclassification.
Using whole genome sequencing (WGS), we provide direct evidence of waning vaccine effectiveness and variant-specific immune evasion during the Delta wave. Effectiveness estimates against calendar-period-classified infections approximated estimates against WGS-classified infections; however, calendar-period classification was associated with variant misclassification. Background The impact variant-specific immune evasion and waning protection have on declining coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) remains unclear. Using whole-genome sequencing (WGS), we examined the contribution these factors had on the decline that followed the introduction of the Delta variant. Furthermore, we evaluated calendar-period-based classification as a WGS alternative. Methods We conducted a test-negative case-control study among people tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 April and 24 August 2021. Variants were classified using WGS and calendar period. Results We included 2029 cases (positive, sequenced samples) and 343 727 controls (negative tests). VE 14-89 days after second dose was significantly higher against Alpha (84.4%; 95% confidence interval [CI], 75.6%-90.0%) than Delta infection (68.9%; 95% CI, 58.0%-77.1%). The odds of Delta infection were significantly higher 90-149 than 14-89 days after second dose (P value = .003). Calendar-period-classified VE estimates approximated WGS-classified estimates; however, calendar-period-based classification was subject to misclassification (35% Alpha, 4% Delta). Conclusions Both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While calendar-period-classified VE estimates mirrored WGS-classified estimates, our analysis highlights the need for WGS when variants are cocirculating and misclassification is likely.
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