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Cited by 603SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesCOVID-19 epidemiological studies

The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index; 4 of the 34 sources its claims cite were checked for support.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Open access
Emary, Katherine R W, Golubchik, Tanya, Aley, Parvinder K, Ariani, Cristina V, Angus, Brian, Bibi, Sagida, Blane, Beth, Bonsall, David, Cicconi, Paola, Charlton, Sue, Clutterbuck, Elizabeth A, Collins, Andrea M, Cox, Tony, Darton, Thomas C, Dold, Christina, Douglas, Alexander D, Duncan, Christopher J A, Ewer, Katie J, Flaxman, Amy L, Faust, Saul N, Ferreira, Daniela M, Feng, Shuo, Finn, Adam, Folegatti, Pedro M, Fuskova, Michelle, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hallis, Bassam, Heath, Paul T, Hay, Jodie, Hill, Helen C, Jenkin, Daniel, Kerridge, Simon, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Ludden, Catherine, Marchevsky, Natalie G, Minassian, Angela M, McGregor, Alastair C, Mujadidi, Yama F, Phillips, Daniel J, Plested, Emma, Pollock, Katrina M, Robinson, Hannah, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sutherland, Rebecca K, Thomson, Emma C, Toshner, Mark, Turner, David P J, Vekemans, Johan, Villafana, Tonya L, Williams, Christopher J, Hill, Adrian V S, Lambe, Teresa, Gilbert, Sarah C, Voysey, Merryn, Ramasamy, Maheshi N, Pollard, Andrew J·2021·The Lancet
DOI 10.1016/s0140-6736(21)00628-0PMC PMC8009612
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Abstract

BACKGROUND: A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant. METHODS: Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 - relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18-55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2-11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6-84·5) for B.1.1.7 and 81·5% (67·9-89·4) for non-B.1.1.7 lineages. INTERPRETATION: ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2. FUNDING: UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a post-hoc exploratory analysis of the UK COV002 randomised trial, ChAdOx1 nCoV-19 showed reduced in-vitro neutralisation against the B.1.1.7 variant but retained clinical efficacy against symptomatic COVID-19 caused by B.1.1.7. Vaccine efficacy was 70·4% against symptomatic B.1.1.7 infection versus 81·5% against non-B.1.1.7 lineages.

Key findings

  • Clinical vaccine efficacy against symptomatic NAAT-positive COVID-19 was 70·4% (95% CI 43·6–84·5) for B.1.1.7 and 81·5% (67·9–89·4) for non-B.1.1.7 lineages.
  • Neutralising antibody activity was lower against B.1.1.7 than against the Victoria lineage: geometric mean ratio 8·9 (95% CI 7·2–11·0); geometric mean titre 58 (95% CI 44–77) for B.1.1.7 versus 517 (424–631) for Victoria.
  • For any NAAT-positive infection, vaccine efficacy was 61·7% (36·7–76·9) against B.1.1.7 and 77·3% (65·4–85·0) against other variants.
  • Vaccinated participants had higher minimum Ct values (median 28·8, IQR 20·5–33·5) than controls (20·2, 15·5–29·6; p<0·0001) and shorter NAAT positivity (median 1·0 week vs 2·0 weeks).

Methods

  • Single-blind, multicentre, randomised phase 2/3 trial (COV002) in the UK; 8534 participants in efficacy cohorts, adults aged ≥18 years at 19 sites, randomly assigned 1:1 to ChAdOx1 nCoV-19 or MenACWY control, with a subset receiving a low-dose first dose.
  • Participants provided weekly self-collected nose/throat swabs and symptomatic swabs; samples were tested by NAAT and positive samples sequenced through the COVID-19 Genomics UK consortium; neutralising responses were measured by live-virus microneutralisation against B.1.1.7 and Victoria.
  • Efficacy analysis included symptomatic COVID-19 in seronegative participants more than 14 days after a second dose; vaccine efficacy was calculated as 1 − relative risk from a robust Poisson regression model with follow-up time offset.

Limitations

  • The paper states that sequences could not be obtained from all positive swabs due to logistical constraints, sample size was determined by sequence availability, and there were no hospitalisations or deaths, so efficacy on those endpoints cannot be assessed.
  • The paper states that samples with high Ct values (>30) were not routinely sequenced, limiting lineage assessment of low viral load specimens over-represented in asymptomatic participants; heterogeneous sequencing data warrant caution, and false-positive NAAT results could affect unsequenced asymptomatic efficacy estimates.
  • The paper states it cannot rule out an 11% reduction in efficacy between B.1.1.7 and non-B.1.1.7 variants; evident from the text, this was an exploratory post-hoc analysis not powered for variant-specific comparisons, with wide and overlapping CIs for asymptomatic/unknown infections.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(21)00628-0

Cites

0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Figure 1 Flow diagram of swabs included in the analysis
Figure 1 Flow diagram of swabs included in the analysisCC BY · PubMed Central
Figure 2 Consensus phylogeny of SARS-CoV-2 genomes identified in this study Clades are coloured by variant lineage and tips are coloured by vaccine allocation. Only genomes with at least 40% coverage are included (n=247). Lineages were assigned by Pangolin version 2.1.7 (lineages version 2021–02–12).
Figure 2 Consensus phylogeny of SARS-CoV-2 genomes identified in this study Clades are coloured by variant lineage and tips are coloured by vaccine allocation. Only genomes with at least 40% coverage are included (n=247). Lineages were assigned by Pangolin version 2.1.7 (lineages version 2021–02–12).CC BY · PubMed Central
Figure 3 Weekly and cumulative number of B.1.1.7 and non-B.1.1.7 isolates identified in the UK trial between Oct 1, 2020, and Jan 14, 2021 Bars show overall weekly case counts (left axis) and lines show cumulative case counts (right axis).
Figure 3 Weekly and cumulative number of B.1.1.7 and non-B.1.1.7 isolates identified in the UK trial between Oct 1, 2020, and Jan 14, 2021 Bars show overall weekly case counts (left axis) and lines show cumulative case counts (right axis).CC BY · PubMed Central
Figure 4 Minimum Ct values across all NAAT positive swabs Ct values from positive NAATs performed at Lighthouse Laboratories using a ThermoFisher TaqPath three-gene assay. Each datapoint represents one participant. For each participant, the minimum of the Ct value for the N gene and ORF1ab gene was taken for each NAAT positive swab, and the minimum across all swabs for the same participant was calculated as a proxy for maximum viral load. Low Ct values are associated with a higher viral load. The midlines of the boxes show medians and the outer bounds of the boxes show IQRs. Error bars show the most extreme point within 1.5 × IQR above or below the 75th or 25th percentile. Ct=cycle threshold. NAAT=nucleic acid amplification test.
Figure 4 Minimum Ct values across all NAAT positive swabs Ct values from positive NAATs performed at Lighthouse Laboratories using a ThermoFisher TaqPath three-gene assay. Each datapoint represents one participant. For each participant, the minimum of the Ct value for the N gene and ORF1ab gene was taken for each NAAT positive swab, and the minimum across all swabs for the same participant was calculated as a proxy for maximum viral load. Low Ct values are associated with a higher viral load. The midlines of the boxes show medians and the outer bounds of the boxes show IQRs. Error bars show the most extreme point within 1.5 × IQR above or below the 75th or 25th percentile. Ct=cycle threshold. NAAT=nucleic acid amplification test.CC BY · PubMed Central
Figure 5 Length of the NAAT-positive period per participant Three primary symptomatic participants who received ChAdOx1 nCoV-19 remained NAAT positive for 8, 9, and 11 weeks, respectively, and one primary symptomatic participant who received the control vaccine remained NAAT positive for 11 weeks; these cases are not shown in the figure. NAAT=nucleic acid amplification test.
Figure 5 Length of the NAAT-positive period per participant Three primary symptomatic participants who received ChAdOx1 nCoV-19 remained NAAT positive for 8, 9, and 11 weeks, respectively, and one primary symptomatic participant who received the control vaccine remained NAAT positive for 11 weeks; these cases are not shown in the figure. NAAT=nucleic acid amplification test.CC BY · PubMed Central
Figure 6 Live-virus microneutralisation antibody titres of sera against B.1.1.7 and a canonical non-B.1.1.7 strain (Victoria) The geometric mean titre is 58 (95% CI 44–77) for B.1.1.7 and 517 (424–631) for Victoria. The geometric mean ratio (Victoria vs B.1.1.7) is 8·9 (95% CI 7·2–11·0). The midlines of the boxes show medians and the outer bounds of the boxes show IQRs. Error bars show the most extreme point within 1·5 × IQR above or below the 75th or 25th percentile. Lines connect samples from the same participant collected at the same trial timepoint (n=49). ND50=titre at which 50% virus neutralisation is achieved.
Figure 6 Live-virus microneutralisation antibody titres of sera against B.1.1.7 and a canonical non-B.1.1.7 strain (Victoria) The geometric mean titre is 58 (95% CI 44–77) for B.1.1.7 and 517 (424–631) for Victoria. The geometric mean ratio (Victoria vs B.1.1.7) is 8·9 (95% CI 7·2–11·0). The midlines of the boxes show medians and the outer bounds of the boxes show IQRs. Error bars show the most extreme point within 1·5 × IQR above or below the 75th or 25th percentile. Lines connect samples from the same participant collected at the same trial timepoint (n=49). ND50=titre at which 50% virus neutralisation is achieved.CC BY · PubMed Central

Verification

Claims the paper makes

38 Own result · 19 Own interpretation · 18 Not checked yet · 15 Own method · 3 Sources not found · 2 Supported · 2 No basis given · 1 Partly supported · accuracy not yet measured

Verify all 26 references — free account

Show all 42 claims

  • It may state two separate claims as one. 35
  • Probably not a substantial claim. 32
56 of 56

  • The paper relies on this without support.

    The meningococcal group A, C, W, and Y conjugate vaccine (MenACWY) used as control does not affect SARS-CoV-2 infection or COVID-19 disease.

    “or a meningococcal group A, C, W, and Y conjugate vaccine (MenACWY) as control”

  • The paper relies on this without support.

    The sequenced subset of NAAT-positive cases is representative of all NAAT-positive cases with respect to SARS-CoV-2 variant and vaccine group.

    “Of these, 401 swabs from 311 participants were successfully sequenced.”

  • The paper relies on this without support.

    Vaccine efficacy observed in the trial participants can be generalised to mass vaccination programmes.

    “These findings support the ongoing use of ChAdOx1 nCoV-19 in mass vaccination programmes to both prevent symptomatic B.1.1.7 disease and reduce the opportunity for viral transmission.”

  • The authors state this as an assumption.

    The false-positive rate in the community testing is 0.1%.

    “Assuming a low false-positive rate of 0·1%, this equates to 200 false-positive swabs, which could skew an attempt to estimate vaccine efficacy.”

  • The paper relies on this without support.

    The Victoria lineage is phylogenetically similar to the original Wuhan outbreak lineage and has only a single mutation in spike protein (S247R; Ser247Arg).

    “The Victoria lineage is phylogenetically similar to the original Wuhan outbreak lineage and has only a single mutation in spike protein (S247R; Ser247Arg).”

  • The paper relies on this without support.

    The peptide pools most frequently recognised by vaccine-elicited T cells span amino acids 311–430 and 101–200 of the S1 domain, which are unaffected by the mutations seen in B.1.1.7.

    “We have previously shown that the peptide pools most frequently recognised by vaccine-elicited T cells span amino acids 311–430 and 101–200 of the S1 domain, which are unaffected by the mutations seen in B.1.1.7.”
6 of 6

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Citations

Cites

Show all 54 references

Research works printed but not linked: 5

  1. Bal, 2021, Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69-V70, France, August to December 2020, medRxiv
  2. Harrington, 2021, Confirmed reinfection with SARS-CoV-2 variant VOC-202012/01, Clin Infect Dis, 10.1093/cid/ciab014 · DOI
  3. Collier, 2021, Impact of SARS-CoV-2 B.1.1.7 spike variant on neutralisation potency of sera from individuals vaccinated with Pfizer vaccine BNT162b2, medRxiv
  4. Xie, 2021, Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera, bioRxiv
  5. Lythgoe, 2020, Within-host genomics of SARS-CoV-2, bioRxiv

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Metadata

Authors
Emary, K. R. W., Golubchik, T., Aley, P. K., Ariani, C. V., Angus, B., Bibi, S., Blane, B., Bonsall, D., Cicconi, P., Charlton, S., Clutterbuck, E. A., Collins, A. M., Cox, T., Darton, T. C., Dold, C., Douglas, A. D., Duncan, C. J. A., Ewer, K. J., Flaxman, A. L., Faust, S. N., Ferreira, D. M., Feng, S., Finn, A., Folegatti, P. M., Fuskova, M., Galiza, E., Goodman, A. L., Green, C. M., Green, C. A., Greenland, M., Hallis, B., Heath, P. T., Hay, J., Hill, H. C., Jenkin, D., Kerridge, S., Lazarus, R., Libri, V., Lillie, P. J., Ludden, C., Marchevsky, N. G., Minassian, A. M., McGregor, A. C., Mujadidi, Y. F., Phillips, D. J., Plested, E., Pollock, K. M., Robinson, H., Smith, A., Song, R., Snape, M. D., Sutherland, R. K., Thomson, E. C., Toshner, M., Turner, D. P. J., Vekemans, J., Villafana, T. L., Williams, C. J., Hill, A. V. S., Lambe, T., Gilbert, S. C., Voysey, M., Ramasamy, M. N., & Pollard, A. J.
Affiliations
  • University of Oxford (GB)
  • Wellcome Sanger Institute (GB)
  • University of Cambridge (GB)
  • Centre for Human Genetics (GB)
  • Public Health England (GB)
  • Liverpool School of Tropical Medicine (GB)
  • Sheffield Teaching Hospitals NHS Foundation Trust (GB)
  • Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
  • University Hospital Southampton NHS Foundation Trust (GB)
  • University Hospitals Bristol and Weston NHS Foundation Trust (GB)
  • St George's, University of London (GB)
  • St Thomas' Hospital (GB)
  • University Hospitals Birmingham NHS Foundation Trust (GB)
  • Queen Elizabeth University Hospital (GB)
  • North Bristol NHS Trust (GB)
  • National Institute for Health and Care Research (GB)
  • London North West Healthcare NHS Trust (GB)
  • NIHR Imperial Biomedical Research Centre (GB)
  • Western General Hospital (GB)
  • Nottingham University Hospitals NHS Trust (GB)
  • AstraZeneca (United States) (US)
  • Aneurin Bevan University Health Board (GB)
Corresponding author
Ramasamy, Maheshi N
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2021-04
Volume
397
Issue
10282
Pages
1351-1362
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(21)00628-0
PMC
PMC8009612
OpenAlex
W3152490217
Cited by
603
References
71
Citations by year
2026: 3 · 2025: 19 · 2024: 35 · 2023: 76 · 2022: 211 · 2021: 257
FWCI
45.85
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • Northumbria Research Link (Northumbria University) (acceptedVersion)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • United Kingdom Department of Health and Social Care
  • Coalition for Epidemic Preparedness Innovations
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
Keywords
ChAdOx1 nCoV-19 vaccine, AZD1222, SARS-CoV-2, B.1.1.7 variant, COVID-19 vaccine efficacy, adenovirus vector vaccine, neutralizing antibodies, breakthrough infection, viral load, viral shedding, booster vaccination, post hoc analysis
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, COVID-19 Nucleic Acid Testing, ChAdOx1 nCoV-19, Adolescent, Adult, Female, United Kingdom, Humans, Male, Middle Aged, Single-Blind Method, Viral Load, Nucleic Acid Amplification Techniques, Young Adult, Antibodies, Neutralizing, Pandemics

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