Cited by 1,031SARS-CoV-2 and COVID-19 ResearchVaccine Coverage and HesitancyCOVID-19 Clinical Research Studies

The DOI matches its Crossref record; 27 of the 31 references it cites were found in a registry or an index; 4 of the 30 sources its claims cite were checked for support.

Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study

Open access

Abstract

Background The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. Methods In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m 2 vs ≥30 kg/m 2 ), and comorbidities (binary variable, with or without comorbidities). Findings Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days. Interpretation Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. Funding ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In UK users of the COVID Symptom Study app, self-reported side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination were less frequent than in phase 3 trials and were mostly mild and short-lived. Both vaccines were associated with reduced SARS-CoV-2 infection risk starting 12 days after the first dose.

Key findings

  • Among 627,383 vaccinated individuals reporting 655,590 doses, systemic side-effects occurred in 13.5% after first-dose BNT162b2, 22.0% after second-dose BNT162b2, and 33.7% after first-dose ChAdOx1 nCoV-19; local side-effects occurred in 71.9%, 68.5%, and 58.7%, respectively.
  • Side-effects were more common in people with previous SARS-CoV-2 infection: systemic effects were 1.6 times higher after first-dose ChAdOx1 and 2.9 times higher after first-dose BNT162b2; local effects were 1.4 times and 1.2 times higher, respectively.
  • Infection risk reductions versus unvaccinated controls began at 12 days: BNT162b2 reduced risk by 58% (95% CI 54–62) at 12–20 days, 69% (66–72) at 21–44 days, and 72% (63–79) at 45–59 days; ChAdOx1 reduced risk by 39% (21–53) at 12–20 days and 60% (49–68) at 21–44 days.
  • Overall, 3106 of 103,622 vaccinated individuals and 50,340 of 464,356 unvaccinated controls tested positive for SARS-CoV-2.

Methods

  • Prospective observational study using self-reported data from the UK COVID Symptom Study app between Dec 8, 2020, and March 10, 2021; participants reported vaccination and side-effects within 8 days, and a subset reported PCR or lateral flow test results after vaccination.
  • Side-effect analyses adjusted for age (≤55 vs >55 years), sex, health-care worker status, obesity (BMI <30 vs ≥30 kg/m²), and comorbidities using Pearl’s back-door adjustment; infection analyses used Poisson regressions adjusted for testing and incidence.
  • Infection rates in vaccinated individuals were compared with unvaccinated app users who reported a COVID-19 test in the same week as a vaccinated user.

Limitations

  • The paper states that self-reported data can introduce information bias, misclassification, or exposure bias; app users were a self-selected group not representative of the general population; collider bias is possible; ChAdOx1 recipients had not received two doses at the time; reporting completeness was higher for systemic than local effects; severe side-effects might have been missed if users could not report them; testing selection bias is possible; the observational design does not allow causal inference; only short-term adverse effects were evaluated; side-effects within 1 week may not be vaccine related; and power was insufficient to assess differential rates by ethnic group.
  • The text also makes evident that previous infection status and test results relied on self-report, and stratified infection models pooled vaccine types because some strata had relatively small sample sizes.

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

Integrity signals

Registry

Crossref · 10.1016/s1473-3099(21)00224-3

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Figure 1 Proportion of participants self-reporting adverse effects to the COVID Symptom Study app within 8 days after vaccination The top row shows systemic effects and the bottom row shows local effects within 8 days after receipt of the first dose (A, D) or second dose (B, E) of the BNT162b2 vaccine or the first dose of the ChAdOx1 nCoV-19 vaccine (C, F). Shading indicates 95% CIs.
Figure 1 Proportion of participants self-reporting adverse effects to the COVID Symptom Study app within 8 days after vaccination The top row shows systemic effects and the bottom row shows local effects within 8 days after receipt of the first dose (A, D) or second dose (B, E) of the BNT162b2 vaccine or the first dose of the ChAdOx1 nCoV-19 vaccine (C, F). Shading indicates 95% CIs.CC BY · PubMed Central
Figure 2 Comparison of adverse effects self-reported to the COVID Symptom Study app between vaccine types and doses ORs for comparisons of the first or second doses of BNT162b2 versus the first dose of ChAdOx1 nCoV-19 were adjusted using Pearl's back-door method.16 OR=odds ratio.
Figure 2 Comparison of adverse effects self-reported to the COVID Symptom Study app between vaccine types and doses ORs for comparisons of the first or second doses of BNT162b2 versus the first dose of ChAdOx1 nCoV-19 were adjusted using Pearl's back-door method.16 OR=odds ratio.CC BY · PubMed Central
Figure 3 Adverse effects self-reported to the COVID Symptom Study app after COVID-19 vaccination, stratified by sex, age, BMI, health status, and previous SARS-CoV-2 test status Proportions with systemic adverse effects (A, C, E) and local adverse effects (B, D, F) are shown. Error bars represent 95% CIs. Numbers in each strata are reported in the appendix (pp 13–14). BMI=body-mass index. *p<0·01. †p<0·05.
Figure 3 Adverse effects self-reported to the COVID Symptom Study app after COVID-19 vaccination, stratified by sex, age, BMI, health status, and previous SARS-CoV-2 test status Proportions with systemic adverse effects (A, C, E) and local adverse effects (B, D, F) are shown. Error bars represent 95% CIs. Numbers in each strata are reported in the appendix (pp 13–14). BMI=body-mass index. *p<0·01. †p<0·05.CC BY · PubMed Central
Figure 4 Infection risk reduction after the first dose in app users who have been vaccinated and subsequently tested, as a function of days since vac The bar chart represents the risk reduction for infection of the vaccinated groups (those who logged at least one PCR or lateral flow test result after vaccination) compared with the unvaccinated group, by vaccine type and days since vaccination. The black lines show 95% CIs.
Figure 4 Infection risk reduction after the first dose in app users who have been vaccinated and subsequently tested, as a function of days since vac The bar chart represents the risk reduction for infection of the vaccinated groups (those who logged at least one PCR or lateral flow test result after vaccination) compared with the unvaccinated group, by vaccine type and days since vaccination. The black lines show 95% CIs.CC BY · PubMed Central

Verification

Claims the paper makes

63 Own result · 20 Own method · 17 Not checked yet · 9 Own interpretation · 1 Supported so far · 1 Partly supported · 1 No basis given · accuracy not yet measured

Verify all 24 references — free account

Show all 72 claims

  • It may state two separate claims as one. 30
  • Probably not a substantial claim. 15
40 of 40
  • The paper relies on this without support.

    COVID Symptom Study app users are representative of the UK general population.

    “The aim of this study was to investigate the adverse effects and infection rate of vaccinated people in a community (general population app users) scenario.”
  • The paper relies on this without support.

    Self-reported vaccination status, side-effects, and SARS-CoV-2 test results are accurate.

    “The app enables self-reported information related to SARS-CoV-2 infection to be captured.”
  • The paper relies on this without support.

    The adjustment set (age, sex, health-care worker status, obesity, and comorbidities) is sufficient to control for confounding in the observational comparisons.

    “we used Pearl's back-door adjustment16 to account for differences within the populations.”
  • The paper relies on this without support.

    The phase 3 trial populations and side-effect definitions are comparable to the app population, so frequencies can be compared.

    “Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials.”
  • The paper relies on this without support.

    The Poisson regression model correctly specifies the relationship and the included covariates (including incidence) adequately control for temporal and other confounders.

    “we also included incidence as a covariate in the Poisson regression model”
  • The paper relies on this without support.

    Self-reported previous positive PCR or lateral flow result accurately identifies past SARS-CoV-2 infection.

    “previous SARS-CoV-2 infection (based on self-reported previous positive PCR or lateral flow result)”
  • The paper relies on this without support.

    Self-reported adverse effects are accurate enough to estimate their prevalence and associations.

    “We used self-reported data, which can introduce information bias, including misclassification, or effect bias exposure.”
7 of 7

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Citations

Cites

Show all 31 references

Research works printed but not linked: 1

  1. MacKenna, 2021, Trends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23·4 million patients using OpenSAFELY, medRxiv

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Metadata

Authors
Menni, C., Klaser, K., May, A., Polidori, L., Capdevila, J., Louca, P., Sudre, C. H., Nguyen, L. H., Drew, D. A., Merino, J., Hu, C., Selvachandran, S., Antonelli, M., Murray, B., Canas, L. S., Molteni, E., Graham, M. S., Modat, M., Joshi, A. D., Mangino, M., Hammers, A., Goodman, A. L., Chan, A. T., Wolf, J., Steves, C. J., Valdes, A. M., Ourselin, S., & Spector, T. D.
Affiliations
  • King's College London (GB)
  • ZOE (United Kingdom) (GB)
  • Harvard University (US)
  • Broad Institute (US)
  • St Thomas' Hospital (GB)
  • University of Nottingham (GB)
Corresponding author
Menni, Cristina
Venue
The Lancet Infectious Diseases
Publisher
Elsevier BV
Published
2021-07
Volume
21
Issue
7
Pages
939-949
ISSN
1473-3099 (ISSN-L)
OpenAlex
W3158373340
Cited by
1,031
References
31
Citations by year
2026: 18 · 2025: 62 · 2024: 115 · 2023: 243 · 2022: 391 · 2021: 198
FWCI
74.92
Type
journal article
Language
en
Open access
Locations
  • The Lancet Infectious Diseases (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, cc-by)
  • Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
  • IRIS eCampus Telematic University (Università degli Studi eCampus) (submittedVersion)
Funders
  • European Commission
  • Crohn's and Colitis Foundation (AGA2021-5102)
  • Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Chronic Disease Research Foundation
  • British Heart Foundation (MR/M016560/1)
  • American Gastroenterological Association
  • Department of Health and Social Care
  • Wellcome Trust (212904/Z/18/Z, WT203148/Z/16/Z, WT213038/Z/18/Z)
  • Alzheimer's Society
  • King's College London
  • King's College Hospital NHS Foundation Trust
  • American Diabetes Association (7-21-JDFM-005)
  • Engineering and Physical Sciences Research Council
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK40561, K01DK120742)
  • National Institute for Health Research
  • Massachusetts General Hospital
  • UK Research and Innovation
  • NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
  • National Institutes of Health (K23DK125838)
  • Medical Research Council (AS-JF-17-011, MR/V027883/1)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
COVID-19 vaccines, BNT162b2, ChAdOx1 nCoV-19 vaccine, vaccine side effects, vaccine effectiveness, community settings, self-reported symptoms, injection site reactions, systemic side effects, comorbidities, obesity, healthcare workers, lateral flow tests
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, Female, United Kingdom, Humans, Male, Middle Aged, Prospective Studies, Safety, Vaccination, Self Report, Drug-Related Side Effects and Adverse Reactions

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