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Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Chrispin Chaguza; Andreas Coppi; Rebecca Earnest; David Ferguson; Nicholas Kerantzas; Frederick Warner; H. Patrick Young; Mallery I. Breban; Kendall Billig; Robert Tobias Koch; Kien Pham; Chaney C. Kalinich; Isabel M. Ott; Joseph R. Fauver; Anne M. Hahn; Irina R. Tikhonova; Christopher Castaldi; Bony De Kumar; Christian M. Pettker; Joshua L. Warren; Daniel M. Weinberger; Marie L. Landry; David R. Peaper; Wade Schulz; Chantal B.F. Vogels; Nathan D. Grubaugh.
  • Chrispin Chaguza; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Andreas Coppi; Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
  • Rebecca Earnest; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • David Ferguson; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA
  • Nicholas Kerantzas; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA
  • Frederick Warner; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA
  • H. Patrick Young; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA
  • Mallery I. Breban; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Kendall Billig; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Robert Tobias Koch; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Kien Pham; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Chaney C. Kalinich; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Isabel M. Ott; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Joseph R. Fauver; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Anne M. Hahn; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Irina R. Tikhonova; Yale Center for Genome Analysis, Yale University, New Haven, CT, USA
  • Christopher Castaldi; Yale Center for Genome Analysis, Yale University, New Haven, CT, USA
  • Bony De Kumar; Yale Center for Genome Analysis, Yale University, New Haven, CT, USA
  • Christian M. Pettker; Quality and Safety, Yale New Haven Health, New Haven, CT, USA
  • Joshua L. Warren; Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA
  • Daniel M. Weinberger; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Marie L. Landry; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA
  • David R. Peaper; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA
  • Wade Schulz; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA
  • Chantal B.F. Vogels; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
  • Nathan D. Grubaugh; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22269660
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to shape the coronavirus disease 2019 (Covid-19) pandemic. The detection and rapid spread of the SARS-CoV-2 Omicron variant (lineage B.1.1.529) in Botswana and South Africa became a global concern because it contained 15 mutations in the spike protein immunogenic receptor binding domain and was less neutralized by sera derived from vaccinees compared to the previously dominant Delta variant. To investigate if Omicron is more likely than Delta to cause infections in vaccinated persons, we analyzed 37,877 nasal swab PCR tests conducted from 12-26 December 2021 and calculated the test positivity rates for each variant by vaccination status. We found that the positivity rate among unvaccinated persons was higher for Delta (5.2%) than Omicron (4.5%). We found similar results in persons who received a single vaccine dose. Conversely, our results show that Omicron had higher positivity rates than Delta among those who received two doses within five months (Omicron = 4.7% vs. Delta = 2.6%), two doses more than five months ago (4.2% vs. 2.9%), and three vaccine doses (2.2% vs. 0.9%). Our estimates of Omicron positivity rates in persons receiving one or two vaccine doses were not significantly lower than unvaccinated persons but were 49.7% lower after three doses. In comparison, the reduction in Delta positivity rates from unvaccinated to 2 vaccine doses was 45.6-49.6% and to 3 vaccine doses was 83.2%. Despite the higher positivity rates for Omicron in vaccinated persons, we still found that 91.2% of the Omicron infections in our study occurred in persons who were eligible for 1 or more vaccine doses at the time of PCR testing. In conclusion, escape from vaccine-induced immunity likely contributed to the rapid rise in Omicron infections.

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