Association of E484K and L452R spike protein mutations with SARS-CoV-2 infection in vaccinated persons---Maryland, January – May 2021

  1. Kenneth A. Feder
  2. Ami Patel
  3. Venkata R. Vepachedu
  4. Catherine Dominguez
  5. Eric N. Keller
  6. Liore Klein
  7. Curi Kim
  8. Tim Blood
  9. Judie Hyun
  10. Theo Williams
  11. Katherine A. Feldman
  12. Heba H. Mostafa
  13. C. Paul Morris
  14. Jacques Ravel
  15. Monique Duwell
  16. David Blythe
  17. Robert Myers
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Abstract

Background

The E484K and L452R amino acid substitutions on the spike protein of SARS-CoV-2 are associated with reduced neutralization by antibodies from acquired immunity. This study examines the respective association of these mutations with infection in persons who had previously received a COVID-19 vaccine.

Methods

Genetic sequences from SARS-CoV-2 specimens collected from Maryland residents and reported to Maryland Department of Health were linked to vaccination history. The prevalence of infections in fully vaccinated persons -- defined as being at least two weeks past receiving the final scheduled dose of a COVID-19 vaccine series -- was compared between infections caused by viruses carrying E484K to those not carrying E484K, and between infections caused by viruses carrying L452R to those not carrying L452R, using logistic regression to adjust for confounding.

Results

Of 9,048 sequenced SARS-CoV-2 specimens examined, 265 (2.9%) were collected from fully vaccinated persons. In adjusted analysis, the E484K substitution was associated with an increase in the odds of the sequenced specimen being collected from a fully vaccinated person (OR 1.96, 95% CI, 1.36 to 2.83). The L452R mutation was not significantly associated with infections in vaccinated persons (OR 1.07, 95% CI, 0.69 to 1.68).

Conclusion

Though more than 97% of SARS-CoV-2 infections were in persons who were not fully vaccinated, the E484K mutation was associated with increased odds of SARS-CoV-2 infection in vaccinated persons. Linking vaccination and sequencing data can help identify and estimate the impact SARS-CoV-2 mutations may have on vaccine effectiveness.

Summary

In viruses sequenced for Maryland’s routine SARS-CoV-2 genomic surveillance, the spike protein amino acid substitution E484K was more prevalent in viruses that infected vaccinated people than in viruses that infected people who were not vaccinated.

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