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Cited by 1,163SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesAnimal Virus Infections Studies

Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

Open access
Feng, Shuo, Phillips, Daniel J., White, Thomas, Sayal, Homesh, Aley, Parvinder K., Bibi, Sagida, Dold, Christina, Fuskova, Michelle +91 more·2021·Nature Medicine
DOI 10.1038/s41591-021-01540-1PMC PMC8604724
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Abstract

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF 50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.

AI snapshot

Written from the paper’s full text.

TL;DR

In the UK COV002 trial, higher anti-spike IgG, anti-RBD IgG, pseudovirus neutralizing, and live-virus neutralizing antibody levels at 28 days after a second ChAdOx1 nCoV-19 dose were associated with lower risk of symptomatic COVID-19, but not asymptomatic infection. Antibody values corresponding to 80% vaccine efficacy against primary symptomatic COVID-19 were 264 BAU/ml for anti-spike IgG, 506 BAU/ml for anti-RBD IgG, 26 IU/ml for pseudovirus neutralization, and 247 NF50 for live-virus neutralization.

Key findings

  • Among 4,372 participants in the correlates population, there were 174 breakthrough NAAT+ SARS-CoV-2 infections; correlates analysis included 171 cases and 1,404 noncases with at least one assay readout. Risk of symptomatic COVID-19 decreased with increasing anti-spike IgG (P = 0.003), anti-RBD IgG (P = 0.018), pseudovirus neutralization titer (P = 0.005), and live-virus neutralization titer (P < 0.001).
  • The antibody level associated with 80% VE against primary symptomatic COVID-19 was 40,923 AU/ml anti-spike IgG, equivalent to 264 BAU/ml (95% CI: 108, 806); 506 BAU/ml anti-RBD IgG (95% CI: 135, NC); 26 IU/ml pseudovirus neutralization (95% CI: NC, NC); and 247 NF50 live-virus neutralization (95% CI: 101, NC).
  • No significant associations were found between any assay and protection against asymptomatic infection, including in sensitivity analysis restricting to high viral load (all P > 0.05).
  • For symptomatic cases with shortness of breath, 80% VE was achieved at lower immune marker levels than for symptomatic cases in general; no significant associations were observed for symptomatic cases without shortness of breath (all P > 0.05).

Methods

  • Data came from COV002, a phase 2/3 randomized single-blind vaccine efficacy trial across 19 UK sites; participants were randomized to ChAdOx1 nCoV-19 or MenACWY control. The correlates population included baseline SARS-CoV-2 N-protein-seronegative participants with a PB28 visit within 14–42 days after the second dose and follow-up to at least 7 days after PB28; the correlates cohort comprised those with biomarker data.
  • Immune markers measured at PB28 were anti-spike IgG, anti-RBD IgG, pseudovirus neutralization, and live-virus neutralization, converted to WHO international standard units. Outcomes were primary symptomatic COVID-19 (NAAT+ with at least one qualifying symptom) and asymptomatic infection (NAAT+ on weekly self-swab with no symptoms).
  • Log-transformed immune markers were analyzed with generalized additive models for binary outcomes using cubic spline smooths, adjusted for baseline exposure risk and weighted by inverse probability weights for sample availability. Correlates of VE were derived by comparing predicted absolute risk with the MenACWY control population risk; 95% CIs used 10,000 bootstrap samples.

Limitations

  • Stated: analyses were based on a mainly white UK population with cases mostly due to B.1.177 and B.1.1.7 variants, so modeled relationships may not apply where other variants dominate or different neutralization strains are used. Many analyses were conducted and P values are unadjusted for multiple comparisons. Results apply to two doses of ChAdOx1 nCoV-19 and may not apply to a single dose or other COVID-19 vaccines. Age profile was not explored due to few older adults; T cells and humoral–cellular interactions were not evaluated; mechanistic versus nonmechanistic correlates could not be determined. No vaccinated participants were hospitalized, so correlates against severe disease or hospitalization could not be assessed. Wide CIs around estimates should be noted, and no single threshold indicated sterilizing immunity.
  • Evident from the text: the correlates relate to protection against mild disease, defined as NAAT+ with at least one symptom, during the subsequent 4- to 6-month period, and represent antibody levels at 28 days after a second dose rather than at the time of exposure.

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

Integrity signals

Registry

Crossref · 10.1038/s41591-021-01540-1

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 6 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Higher pseudovirus neutralization titer is associated with lower risk of symptomatic COVID-19.

    “The risk of symptomatic COVID-19 decreased with increasing levels of anti-spike IgG (P = 0.003), anti-RBD IgG (P = 0.018), pseudovirus neutralization titer (P = 0.005), and live-virus neutralization titer (P < 0.001)”
    Quote in the paperSubstantial claim
  • Findingown data

    Higher anti-spike IgG levels are associated with lower risk of symptomatic COVID-19.

    “The risk of symptomatic COVID-19 decreased with increasing levels of anti-spike IgG (P = 0.003)”
    Quote in the paperSubstantial claim
  • Findingown data

    Higher live-virus neutralization titer is associated with lower risk of symptomatic COVID-19.

    “The risk of symptomatic COVID-19 decreased with increasing levels of anti-spike IgG (P = 0.003), anti-RBD IgG (P = 0.018), pseudovirus neutralization titer (P = 0.005), and live-virus neutralization titer (P < 0.001)”
    Quote in the paperSubstantial claim
  • Findingown data

    Higher anti-RBD IgG levels are associated with lower risk of symptomatic COVID-19.

    “The risk of symptomatic COVID-19 decreased with increasing levels of anti-spike IgG (P = 0.003), anti-RBD IgG (P = 0.018), pseudovirus neutralization titer (P = 0.005), and live-virus neutralization titer (P < 0.001)”
    Quote in the paperSubstantial claim
  • Findingnone given

    Not all participants with results from the pseudovirus neutralization titer also have results from the anti-spike, anti-RBD, and live neutralizing antibody titers.

    “Not all participants with results from the pseudovirus neutralization titer also have results from the anti-spike, anti-RBD, and live neutralizing antibody titers.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 10
  • Classified as probably not a substantial claim. 23

  • May combine two claims.

    Findingown data

    In the baseline exposure model developed among the MenACWY control group, younger age and being a healthcare worker facing more than one patient with COVID-19 per day were associated with higher risk of being NAAT+.

    “In our baseline exposure model developed among the MenACWY control group, younger age and being a healthcare worker facing more than one patient with COVID-19 per day were associated with a higher risk of being NAAT+.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    Vaccine efficacy against primary symptomatic COVID-19 was modeled as a function of immune markers measured at PB28.

    “VE against primary symptomatic COVID-19 as a function of immune markers measured at PB28.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    The predicted absolute risk of primary symptomatic COVID-19 was modeled as a function of immune markers measured at PB28 using generalized additive regression.

    “Predicted absolute risk of primary symptomatic COVID-19 as a function of immune markers measured at PB28 by generalized additive regression.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    Data were available for at least one of four assay readouts for 171/174 (98.3%) cases and 1,404/4,195 (33.5%) noncases.

    “Data were available for at least one of four assay readouts (anti-spike IgG, anti-receptor binding domain (RBD) IgG, pseudovirus neutralization assay, and live-virus neutralization) for 171 out of 174 (98.3%) cases and 1,404 out of 4,195 (33.5%) noncases.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    People in the case group were younger, with 84.2% aged 18-55 years compared with 71.6% of noncases.

    “People in the case group were younger, with 84.2% being aged 18-55 years, compared with 71.6% of the noncase group”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    People in the case group were more likely to be healthcare workers (62.0% vs 57.5% of noncases).

    “and were more likely to be healthcare workers (62.0% were healthcare workers compared with 57.5% of the noncase group, Table 1).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    The relative risk of primary symptomatic COVID-19 among vaccine recipients compared with MenACWY control arm participants was modeled as a function of immune markers measured at PB28.

    “Relative risk of primary symptomatic COVID-19 among vaccine recipients compared with MenACWY control arm participants as a function of immune markers measured at PB28.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    The relative risk of asymptomatic SARS-CoV-2 infection among vaccine recipients compared with the MenACWY control arm participants was modeled as a function of immune markers measured at PB28.

    “Relative risk of asymptomatic SARS-CoV-2 infection among vaccine recipients compared with the MenACWY control arm participants as a function of immune markers measured at PB28.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    A sensitivity analysis was conducted excluding cases with lower viral loads (CT ≥ 30) to account for potential misclassification in asymptomatic infections.

    “To account for potential of misclassification in asymptomatic infections, a sensitivity analysis was conducted excluding cases with lower viral loads (defined as those for whom all returned PCR positive tests had a CT value ≥ 30), as these are potential false positives.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Reduced neutralizing capacity against B.1.351 and other variants of concern might drive reduced protection against initial infection, and perhaps transmission, but protection against severe disease is maintained.

    “These observations indicate that the reduced neutralizing capacity against B.1.351and other variants of concern, might drive reduced protection against initial infection, and perhaps transmission, but protection against severe disease is maintained.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    A sensitivity analysis showed absolute and relative risk of primary symptomatic SARS-CoV-2 infection with 3 or more COVID-19 symptoms as a function of immune markers measured at day 28 post-second dose.

    “Sensitivity analysis showing absolute and relative risk primary symptomatic SARS-CoV-2 infection with 3 or more COVID-19 symptoms as a function of immune markers measured at day 28 post-second dose.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    A sensitivity analysis was performed to account for the potential bias caused by imputing LLOQ / 2.

    “We performed a sensitivity analysis to account for the potential bias caused by imputing LLOQ / 2.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Correlates may vary according to age profile, but this was not explored in the study due to the small number of older adults recruited.

    “Correlates may also vary according to age profile, but this was not explored in our study due to the small number of older adults recruited.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A sensitivity analysis showed absolute and relative risk of asymptomatic SARS-CoV-2 infection as a function of immune markers measured at 28 days post second dose excluding cases with low viral load (Ct ≥ 30).

    “Sensitivity analysis showing absolute and relative risk of asymptomatic SARS-CoV-2 infection as a function of immune markers measured at 28 days post second dose excluding cases with low viral load (Ct ≥ 30).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A sensitivity analysis showed absolute and relative risk of primary symptomatic SARS-CoV-2 infection in participants with no symptoms of shortness of breath as a function of immune markers measured at day 28 post-second dose.

    “Sensitivity analysis showing absolute and relative risk of primary symptomatic SARS-CoV-2 infection in participants with no symptoms of shortness of breath as a function of immune markers measured at day 28 post-second dose.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A sensitivity analysis showed absolute and relative risk of primary symptomatic SARS-CoV-2 infection in participants with symptoms of shortness of breath as a function of immune markers measured at day 28 post-second dose.

    “Sensitivity analysis showing absolute and relative risk of primary symptomatic SARS-CoV-2 infection in participants with symptoms of shortness of breath as a function of immune markers measured at day 28 post-second dose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    A trial of a new vaccine that works through similar immune mechanisms and produces antibody responses above the correlate values in at least 50% of participants might be expected to have similar efficacy against the clinical endpoints used in the UK trial, and higher efficacy against more severe endpoints.

    “A trial of a new vaccine that works through similar immune mechanisms and which produces antibody responses that are above the correlate values reported here in at least 50% of participants (that is, it has a similar or higher median), might be expected to have similar efficacy against the clinical endpoints used in our UK trial, and higher efficacy against more severe endpoints.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: No study to date has defined a correlate of protection against SARS-CoV-2 infection or disease that can be used by regulators and vaccine developers.

  • May combine two claims.

    Interpretationown data

    The probability of infection decreases on average with higher immune responses, but substantial variation exists between individuals.

    “Instead, the probability of infection decreases on average with higher immune responses, but substantial variation exists between individuals.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The CoR was estimated by GAM adjusting for baseline risk exposure and weighting by inverse probability weights.

    “We then estimated the CoR by GAM, adjusting for the baseline risk exposure and weighting by inverse probability weights.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ChAdOx1 nCoV-19-vaccinated hamsters with low neutralizing titers against B.1.351 were fully protected against LRTI following challenge with B.1.351, despite no evidence of protection against shedding of virus from the upper airway.

    “Similarly, ChAdOx1 nCoV-19-vaccinated hamsters, with low neutralizing titers against B.1.351,were fully protected against LRTI following challenge with B.1.351,despite no evidence of protection against shedding of virus from the upper airway 29 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Fischer, R. J., et al. ChAdOx1 nCoV-19 (AZD1222) protects hamsters against SARS-CoV-2 B.1.351 and B.1.1.7 disease. Nature Comm. (in the press).

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The logit-transformed predicted baseline exposure risk was included as a linear covariate in the GAM model.

    “The logit-transformed predicted baseline exposure risk was included as a linear covariate in the GAM model.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline exposure risk predicted from the MenACWY control population is applicable to the ChAdOx1 nCoV-19 correlates cohort.

  • May combine two claims.

    Premisecitation

    Protection against upper respiratory tract or asymptomatic infections may be more closely associated with the presence of secretory IgA on the mucosal surface, which was not measured in this study.

    “Protection against upper respiratory tract or asymptomatic infections may be more closely associated with the presence of secretory IgA on the mucosal surface which was not measured in this study 30 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Wang, Z. et al. Enhanced SARS-CoV-2 neutralization by dimeric IgA. Sci. Transl. Med. 13, eabf1555 (2021). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Samples were tested blinded to case status.

    “Samples were tested blinded to case status.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Protection against lower respiratory tract infection (LRTI) may be easier to achieve than against upper respiratory tract infection (URTI).

    “It has previously been shown that protection against lower respiratory tract infection (LRTI) may be easier to achieve than against upper respiratory tract infection (URTI), as challenge studies in rhesus macaques have shown stronger correlation between neutralizing titers and the level of subgenomic messenger RNA in bronchoalveolar lavage samples than in nasal swab samples 28 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] van Doremalen, N. et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature 586, 578–582 (2020). source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The analyses are based on cases of COVID-19 detected in a mainly white population in the United Kingdom, mostly due to B.1.177 and B.1.1.7 variants.

    “These analyses are based on cases of COVID-19 detected in a mainly white population in the United Kingdom, which were mostly due to B.1.177and B.1.1.7 variants.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The study was a phase 2/3 randomized single-blind vaccine efficacy trial conducted across 19 sites in the United Kingdom.

    “The data included in this analysis comes from participants enrolled in COV002 (registration NCT04400838), a phase 2/3 randomized single-blind vaccine efficacy trial conducted across 19 sites in the United Kingdom.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Inverse probability weights were calculated for each bootstrap sample to account for sampling bias.

    “For each bootstrap sample, we calculated the inverse probability weights to account for sampling bias.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Brand et al. found single imputation embedded inside a bootstrap showed better statistical properties than other methods when a bootstrap is required for missing data.

    “When a bootstrap is required for missing data, Brand et al. found single imputation embedded inside a bootstrap showed better statistical properties than other methods 43 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Brand, J., van Buuren, S., le Cessie, S. & van den Hout, W. Combining multiple imputation and bootstrap in the analysis of cost‐effectiveness trial data. Stat. Med. 38, 210–220 (2019). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All endpoints were evaluated by a blinded independent clinical review committee.

    “All endpoints were evaluated by a blinded independent clinical review committee.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    These data can be used to extrapolate efficacy estimates for new vaccines that use similar immune mechanisms and where efficacy data are unavailable.

    “These data can be used to extrapolate efficacy estimates for new vaccines that use similar immune mechanisms and where efficacy data is unavailable.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: No study to date has defined a correlate of protection against SARS-CoV-2 infection or disease that can be used by regulators and vaccine developers.

  • May combine two claims.

    Study design and conductown data

    The analyses were conducted on samples taken after two doses of ChAdOx1 nCoV-19 and might not apply to protection afforded by a single dose of the same vaccine or other COVID-19 vaccines.

    “Furthermore, these analyses have been conducted on samples taken after two doses of ChAdOx1 nCoV-19 and might not apply to protection afforded by a single dose of the same vaccine or other COVID-19 vaccines.”
    Quote in the paperNot a substantial claim
31 of 31

  • The authors state this as an assumption.

    The mechanism of missingness for samples that were not tested is missing at random.

    “We assume the mechanism of missingness for samples that were not tested to be missing at random 39 .”

  • The paper relies on this without support.

    No study to date has defined a correlate of protection against SARS-CoV-2 infection or disease that can be used by regulators and vaccine developers.

    “Nevertheless, no study to date has defined a correlate of protection against SARS-CoV-2 infection or disease that can be used by regulators and vaccine developers.”

  • The paper relies on this without support.

    Baseline exposure risk predicted from the MenACWY control population is applicable to the ChAdOx1 nCoV-19 correlates cohort.

    “The linear predictor from the risk model developed using the MenACWY control population was used to predict the baseline risk of exposure in the ChAdOx1 nCoV-19 correlates cohort.”

  • The authors state this as an assumption.

    The confidence ellipses for correlations assume a t-distribution.

    “95% confidence ellipses assuming a t-distribution are shown for each outcome (primary symptomatic cases, asymptomatic cases and negative controls).”
4 of 4

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Cites

Flagged first, then by citations

1 of the 41 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Kemp, A. AZD1222 US Phase III trial met primary efficacy endpoint in preventing COVID-19 at interim analysis. https://www.astrazeneca.com/media-centre/press-releases/2021/astrazeneca-us-vaccine-trial-met-primary-endpoint.html (2021).
  2. Box, G. E. & Tiao, G. C. Bayesian Inference in Statistical Analysis (John Wiley & Sons, 2011).

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Authors
Feng, S., Phillips, D. J., White, T., Sayal, H., Aley, P. K., Bibi, S., Dold, C., Fuskova, M., Gilbert, S. C., Hirsch, I., Humphries, H. E., Jepson, B., Kelly, E. J., Plested, E., Shoemaker, K., Thomas, K. M., Vekemans, J., Villafana, T. L., Lambe, T., Pollard, A. J., Voysey, M., the Oxford COVID Vaccine Trial Group, Adlou, S., Allen, L., Angus, B., Anslow, R., Asselin, M.-C., Baker, N., Baker, P., Barlow, T., Beveridge, A., Bewley, K. R., Brown, P., Brunt, E., Buttigieg, K. R., Camara, S., Charlton, S., Chiplin, E., Cicconi, P., Clutterbuck, E. A., Collins, A. M., Coombes, N. S., Clemens, S. A. C., Davison, M., Demissie, T., Dinesh, T., Douglas, A. D., Duncan, C. J. A., Emary, K. R. W., Ewer, K. J., Felle, S., Ferreira, D. M., Finn, A., Folegatti, P. M., Fothergill, R., Fraser, S., Garlant, H., Gatcombe, L., Godwin, K. J., Goodman, A. L., Green, C. A., Hallis, B., Hart, T. C., Heath, P. T., Hill, H., Hill, A. V. S., Jenkin, D., Kasanyinga, M., Kerridge, S., Knight, C., Leung, S., Libri, V., Lillie, P. J., Marinou, S., McGlashan, J., McGregor, A. C., McInroy, L., Minassian, A. M., Mujadidi, Y. F., Penn, E. J., Petropoulos, C. J., Pollock, K. M., Proud, P. C., Provstgaard-Morys, S., Rajapaska, D., Ramasamy, M. N., Sanders, K., Shaik, I., Singh, N., Smith, A., Snape, M. D., Song, R., Shrestha, S., Sutherland, R. K., Thomson, E. C., Turner, D. P. J., Webb-Bridges, A., Wrin, T., & Williams, C. J.
Affiliations
  • University of Oxford (GB)
  • AstraZeneca (United Kingdom) (GB)
  • Public Health England (GB)
  • AstraZeneca (United States) (US)
  • AstraZeneca (Sweden) (SE)
  • Liverpool School of Tropical Medicine (GB)
  • University of Siena (IT)
  • Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
  • University of Bristol (GB)
  • St Thomas' Hospital (GB)
  • University Hospitals Birmingham NHS Foundation Trust (GB)
  • St George's, University of London (GB)
  • University of Hull (GB)
  • London North West Healthcare NHS Trust (GB)
  • LabCorp (United States) (US)
  • NHS Lothian (GB)
  • Nottingham University Hospitals NHS Trust (GB)
  • Aneurin Bevan University Health Board (GB)
Corresponding author
Voysey, Merryn
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-09-29
Volume
27
Issue
11
Pages
2032-2040
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-021-01540-1
PMC
PMC8604724
OpenAlex
W3174017401
Cited by
1,163
References
41
Citations by year
2026: 36 · 2025: 94 · 2024: 155 · 2023: 255 · 2022: 515 · 2021: 106 · 2020: 1
FWCI
81.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • Liverpool John Moores University (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
DH | National Institute for Health Research (NA)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2, COVID-19 vaccines, vaccine efficacy, binding antibodies, neutralizing antibodies, anti-spike antibodies, anti-RBD antibodies, pseudovirus neutralization, symptomatic infection, asymptomatic infection, Alpha variant, vaccine correlates of protection, vaccine licensure
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Female, United Kingdom, Humans, Immunization, Secondary, Male, Middle Aged, Vaccination, Cohort Studies, Treatment Outcome, Infection Control, Young Adult, Immunity, Humoral, Antibodies, Neutralizing, Asymptomatic Infections, Patient Acuity

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