Efficacy of two doses of COVID-19 vaccine against severe COVID-19 in those with risk conditions and residual risk to the clinically extremely vulnerable: the REACT-SCOT case-control study

  1. Paul M McKeigue
  2. David A McAllister
  3. Chris Robertson
  4. Sharon Hutchinson
  5. Stuart McGurnaghan
  6. Diane Stockton
  7. Helen M Colhoun
  8. for the PHS COVID-19 Epidemiology and Research Cell

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Abstract

Objectives

To determine whether COVID-19 efficacy varies with clinical risk category and to investigate risk factors for severe COVID-19 in those who have received two doses of vaccine.

Design

Matched case-control study (REACT-SCOT).

Setting

Population of Scotland from 1 December 2020 to 8 September 2021.

Main outcome measure

Severe COVID-19, defined as cases with entry to critical care or fatal outcome.

Results

Efficacy against severe COVID-19 of two doses of vaccine was 94% (95 percent CI 93% to 96%) in those without designated risk conditions, 89% (95 percent CI 86% to 91%) in those with moderate risk conditions, but only 73% (95 percent CI 64% to 79%) in those designated as clinically extremely vulnerable (CEV) and eligible for shielding. Of the 641 cases of severe COVID-19 in double-vaccinated individuals, 47% had moderate risk conditions and 38% were CEV. In the double-vaccinated CEV group, the rate ratio for severe disease (with no risk condition as reference category) was highest in solid organ transplants at 101 (95% CI 47 to 214) but even in this subgroup the absolute risk of severe COVID-19 was low (35 cases in 23678 person-months of follow-up).

Conclusions

Two doses of vaccine protect against severe COVID-19 in CEV individuals but the residual risk in double-vaccinated individuals remains far higher in those who are CEV than in those who are not. These results lay a basis for determining eligibility for additional measures including passive immunization to protect those at highest risk.

Article activity feed

  1. Version published to 10.1101/2021.09.13.21262360v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.09.13.21262360: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Statement of principal findings: Strengths and limitations: Strengths of this study are the elimination of calendar time effects by the matched case-control design, the comprehensive linkage to e-health records and the focus on severe cases as main outcome measure. Hospitalised cases may include some test-positive individuals whose admission or continued stay in hospital was for another underlying diagnosis: this in turn may lead to underestimation of vaccine efficacy against COVID-19, especially in risk groups with comorbidities. Such misclassification is less likely to occur with the narrow definition of severe COVID-19 used in the REACT-SCOT study. Even in this large cohort, the numbers of severe cases in some CEV subgroups are too small for vaccine efficacy against severe disease to be estimated accurately within these subgroups. Another limitation is that as most immunosuppressants and drugs for cancer are prescribed only in hospital and where prescribing records are not held in electronic form, we cannot study the relation of risk to different classes of immunosuppressant drugs. The national shielding list does not hold information about drug therapy or diagnoses other than the seven broad categories listed as CEV. Relation to other studies: A recent report based on primary care data examined vaccine efficacy against symptomatic COVID-19 for which a medical consultation was recorded (8). For those who had been advised to shield, the efficacy after two doses of any vacci...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.09.13.21262360v1 on medRxiv