Use of Whole-Genome Sequencing to Estimate the Contribution of Immune Evasion and Waning Immunity on Decreasing COVID-19 Vaccine Effectiveness.

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.

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [e-mail].

Déclaration de conflit d'intérêts

Potential conflicts of interest. A. I. K. serves as an expert panel member for Reckitt Global Hygiene Institute, scientific advisory board member for Revelar Biotherapeutics, and a consultant for Tata Medical and Diagnostics and Regeneron Pharmaceuticals; and has received grants from Merck, Regeneron Pharmaceuticals, and Tata Medical and Diagnostics for research related to COVID-19. W. L. S. was an investigator for a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; is a technical consultant to Hugo Health, a personal health information platform; cofounder of Refactor Health, an AI-augmented data management platform for health care; and has received grants from Merck and Regeneron Pharmaceutical for research related to COVID-19. J. D. H., R. C., S. M., D. F., S. H., and A. Z. are employees and shareholders of Regeneron Pharmaceuticals, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.