PreprintCited by 2,420SARS-CoV-2 and COVID-19 ResearchVaccine Coverage and HesitancyCOVID-19 epidemiological studies

The DOI matches its Crossref record; 28 of the 29 references it cites were found in a registry or an index; 1 of the 44 sources its claims cite were checked for support.

Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern

Open access
Andrews, Nick, Stowe, Julia, Kirsebom, Freja, Toffa, Samuel, Rickeard, Tim, Gallagher, Eileen, Gower, Charlotte, Kall, Meaghan, Groves, Natalie, O’Connell, Anne-Marie, Simons, David, Blomquist, Paula B., Zaidi, Asad, Nash, Sophie, Aziz, Nurin Iwani Binti Abdul, Thelwall, Simon, Dabrera, Gavin, Myers, Richard, Amirthalingam, Gayatri, Gharbia, Saheer, Barrett, Jeffrey C., Elson, Richard, Ladhani, Shamez N, Ferguson, Neil, Zambon, Maria, Campbell, Colin NJ, Brown, Kevin, Hopkins, Susan, Chand, Meera, Ramsay, Mary, Bernal, Jamie Lopez·2021·New England Journal of Medicine

Abstract

Background: A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. Methods: We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. Results: Between 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. Conclusions: Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.

Overview

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Written from the paper’s full text.

TL;DR

In England, a test-negative case–control study found that COVID-19 vaccine effectiveness against symptomatic omicron infection was substantially lower than against delta and waned rapidly after two doses. Booster doses with BNT162b2 or mRNA-1273 restored substantial protection, but this protection also declined over the short follow-up period.

Key findings

  • Among 886,774 eligible omicron cases, 204,154 delta cases, and 1,572,621 test-negative controls, vaccine effectiveness against symptomatic disease was higher for delta than omicron at all time points and for all primary-course/booster combinations.
  • After two BNT162b2 doses, omicron vaccine effectiveness was 65.5% (95% CI, 63.9–67.0) at 2–4 weeks, falling to 8.8% (95% CI, 7.0–10.5) at ≥25 weeks; after two ChAdOx1 nCoV-19 doses, no effect against omicron was noted from 20 weeks.
  • A BNT162b2 booster after ChAdOx1 nCoV-19 increased omicron vaccine effectiveness to 62.4% (95% CI, 61.8–63.0) at 2–4 weeks, decreasing to 39.6% (95% CI, 38.0–41.1) at ≥10 weeks; after BNT162b2 primary course, it increased to 67.2% (95% CI, 66.5–67.8) and declined to 45.7% (95% CI, 44.7–46.7).
  • An mRNA-1273 booster after ChAdOx1 nCoV-19 increased omicron vaccine effectiveness to 70.1% (95% CI, 69.5–70.7) at 2–4 weeks and decreased to 60.9% (95% CI, 59.7–62.1) at 5–9 weeks; after BNT162b2 primary course, it increased to 73.9% (95% CI, 73.1–74.6) and fell to 64.4% (95% CI, 62.6–66.1) at 5–9 weeks.

Methods

  • Test-negative case–control design in England comparing odds of vaccination in symptomatic PCR-positive SARS-CoV-2 cases with symptomatic test-negative controls, using data from November 27, 2021, to January 12, 2022.
  • Cases were classified as omicron or delta by whole-genome sequencing, genotyping, or S target–negative status; vaccination data came from the National Immunization Management System, with 91.8% of eligible tests linked.
  • Logistic regression estimated vaccine effectiveness adjusted for age, sex, deprivation, race/ethnic group, foreign travel, geographic region, test date, health/social care worker status, clinical risk group, clinically extremely vulnerable status, and previous positive test.

Limitations

  • The authors state they could not determine protection against severe disease because of the small number of omicron hospitalizations and the natural lag between infection and severe outcomes.
  • The authors note possible residual confounding from travelers and contacts of travelers, uncertainty from relatively small omicron case numbers, inability to break down estimates by age and clinical risk group, a small and potentially different unvaccinated comparator group, short follow-up after booster vaccination, and possible misclassification from PCR testing and S target–negative status.
  • The authors also state that populations receiving different vaccines or boosters differed, and that the ChAdOx1 nCoV-19 booster analysis was particularly likely to be biased because this vaccine was not recommended as a booster in the United Kingdom; the observational design makes confounding by indication evident.

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Integrity signals

Registry

Crossref · 10.1101/2021.12.14.21267615

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    Recent analyses using different control groups have shown good concordance between analyses using an unvaccinated control group and analyses estimating relative vaccine effectiveness among persons who have received a booster dose as compared with those who have received two doses.

    “Furthermore, recent analyses using different control groups have shown good concordance between analyses using an unvaccinated control group and analyses estimating relative vaccine effectiveness among persons who have received a booster dose as compared with those who have received two doses.”
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Metadata

Authors
Andrews, N., Stowe, J., Kirsebom, F., Toffa, S., Rickeard, T., Gallagher, E., Gower, C., Kall, M., Groves, N., O’Connell, A.-M., Simons, D., Blomquist, P. B., Zaidi, A., Nash, S., Aziz, N. I. B. A., Thelwall, S., Dabrera, G., Myers, R., Amirthalingam, G., Gharbia, S., Barrett, J. C., Elson, R., Ladhani, S. N., Ferguson, N., Zambon, M., Campbell, C. N., Brown, K., Hopkins, S., Chand, M., Ramsay, M., & Bernal, J. L.
Affiliations
St George's, University of London (GB)
Corresponding author
Bernal, Jamie Lopez
Venue
New England Journal of Medicine
Publisher
openRxiv
Published
2021-12-14
Volume
386
Issue
16
Pages
1532-1546
ISSN
0028-4793 (ISSN-L)
OpenAlex
W4214863616
Cited by
2,420
References
24
Citations by year
2026: 100 · 2025: 212 · 2024: 394 · 2023: 766 · 2022: 928 · 2021: 19
FWCI
281.11
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • UEA Digital Repository (University of East Anglia) (submittedVersion)
Funders
  • Wellcome Trust
  • National Institute for Health and Care Research (NIHR201395)
  • Medical Research Council (MR/R015600/1)
  • Biotechnology and Biological Sciences Research Council (BB/M009513/1)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
Keywords
COVID-19 vaccine effectiveness, Omicron variant, Delta variant, BNT162b2, ChAdOx1 nCoV-19 vaccine, mRNA-1273, booster vaccination, waning vaccine effectiveness, symptomatic infection, test-negative case-control design
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, Vaccine Efficacy, BNT162 Vaccine, 2019-nCoV Vaccine mRNA-1273, ChAdOx1 nCoV-19, Humans, Immunization, Secondary, Case-Control Studies

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