Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom

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Abstract

The effectiveness of COVID-19 vaccination in preventing new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the general community is still unclear. Here, we used the Office for National Statistics COVID-19 Infection Survey—a large community-based survey of individuals living in randomly selected private households across the United Kingdom—to assess the effectiveness of the BNT162b2 (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value (<30 versus ≥30; as a surrogate for viral load) and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 real-time PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 d after the first dose (61% (95% confidence interval (CI) = 54–68%) versus 66% (95% CI = 60–71%), respectively), with greater reductions observed after a second dose (79% (95% CI = 65–88%) versus 80% (95% CI = 73–85%), respectively). The largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of a difference between the BNT162b2 and ChAdOx1 vaccines.

Abstract

Results from the Office of National Statistics COVID-19 Infection Survey in the United Kingdom demonstrate that the ChAdOx1 nCoV-19 and BNT162b2 vaccines reduce the incidence of new SARS-CoV-2 infections by up to 65% with a single dose and up to 80% after two doses, with no significant differences in efficacy observed between the two vaccines.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Merryn Voysey, Sue Ann Costa Clemens, Shabir Madhi … (2022)

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

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BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

Noa Dagan, Noam Barda, Eldad Kepten … (2021)

Abstract Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Methods All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19–related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan–Meier estimator. Results Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions. Conclusions This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.

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Author and article information

Contributors

Koen B. Pouwels:

ORCID: http://orcid.org/0000-0001-7097-8950

koen.pouwels@ndph.ox.ac.uk

Journal

Journal ID (nlm-ta): Nat Med

Journal ID (iso-abbrev): Nat Med

Title: Nature Medicine

Publisher: Nature Publishing Group US (New York )

ISSN (Print): 1078-8956

ISSN (Electronic): 1546-170X

Publication date (Electronic): 9 June 2021

Publication date PMC-release: 9 June 2021

Publication date (Print): 2021

Volume: 27

Issue: 8

Pages: 1370-1378

Affiliations

[1 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Medicine, , University of Oxford, ; Oxford, UK

[2 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, , University of Oxford, ; Oxford, UK

[3 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, NIHR Oxford Biomedical Research Centre, , University of Oxford, ; Oxford, UK

[4 ]GRID grid.8348.7, ISNI 0000 0001 2306 7492, Department of Infectious Diseases and Microbiology, Oxford, , University Hospitals NHS Foundation Trust, John Radcliffe Hospital, ; Oxford, UK

[5 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Big Data Institute, Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK

[6 ]GRID grid.426100.1, ISNI 0000 0001 2157 6840, Office for National Statistics, ; Newport, UK

[7 ]GRID grid.5379.8, ISNI 0000000121662407, Department of Mathematics, , University of Manchester, ; Manchester, UK

[8 ]IBM Research, Hartree Centre, Daresbury, UK

[9 ]Glasgow Lighthouse Laboratory, Glasgow, UK

[10 ]BioClavis, Glasgow, UK

[11 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Office of the Regius Professor of Medicine, , University of Oxford, ; Oxford, UK

[12 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Health Improvement Directorate, Public Health England, ; London, UK

[13 ]GRID grid.52788.30, ISNI 0000 0004 0427 7672, Wellcome Trust, ; London, UK

[14 ]GRID grid.83440.3b, ISNI 0000000121901201, MRC Clinical Trials Unit at UCL, , University College London, ; London, UK

[15 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Health Economics Research Centre, Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK

Author information

Nicole Stoesser http://orcid.org/0000-0002-4508-7969

Koen B. Pouwels http://orcid.org/0000-0001-7097-8950

Article

Publisher ID: 1410

DOI: 10.1038/s41591-021-01410-w

PMC ID: 8363500

PubMed ID: 34108716

SO-VID: eb76effb-3dab-4a2d-9f17-32506acdde57

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 6 May 2021

Date accepted : 26 May 2021

Funding

Funded by: This study is funded by the Department of Health and Social Care with in-kind support from the Welsh Government, the Department of Health on behalf of the Northern Ireland Government and the Scottish Government. KBP is also supported by the Huo Family Foundation.

Funded by: FundRef https://doi.org/10.13039/501100000272, DH | National Institute for Health Research (NIHR);

Award ID: NIHR200915

Award Recipient : Emma Pritchard Nicole Stoesser David W. Eyre Tim E. A. Peto A. Sarah Walker

Funded by: EP is also supported by the Huo Family Foundation.

Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);

Award ID: 110110/Z/15/Z

Award Recipient : Philippa C. Matthews

Funded by: NIHR Oxford BRC Senior Fellowship award

Funded by: DWE is supported by a Robertson Fellowship and an NIHR Oxford BRC Senior Fellowship

Funded by: TEAP is also supported by the NIHR Oxford Biomedical Research Centre

Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);

Award ID: MC_UU_12023/22

Award Recipient : A. Sarah Walker

Funded by: ASW is also supported by the NIHR Oxford Biomedical Research Centre and is an NIHR Senior Investigator

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ScienceOpen disciplines: Medicine

Keywords: viral infection,epidemiology,outcomes research

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ScienceOpen disciplines: Medicine

Keywords: viral infection, epidemiology, outcomes research

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Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom

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Most cited references 23

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

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