Reinfection with SARS-CoV-2: outcome, risk factors and vaccine efficacy in a Scottish cohort

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

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Abstract

Background

The objective of this study was to investigate how protection against COVID-19 conferred by previous infection is modified by vaccination.

Methods

In a cohort of all 152655 individuals in Scotland alive at 90 days after a positive test for SARS-CoV-2 (confirmed by cycle threshold < 30, or two tests) followed till 22 September 2021, rate ratios for reinfection were estimated with calendar time or tests as timescale.

Findings

Rates of detected and hospitalised reinfection with COVID-19 while unvaccinated were respectively 6.8 (95% CI 6.4 to 7.2) and 0.18 (95% CI 0.12 to 0.25) per 1000 person-months. These rates were respectively 68% and 74% lower than in a matched cohort of individuals who had not previously tested positive. Efficacy of two doses of vaccine in those with previous infection was estimated as as 84% (95 percent CI 81% to 86%) against detected reinfection and 71% (95 percent CI 29% to 88%) against hospitalised or fatal reinfection. The rate of detected reinfection after two doses of vaccine was 1.35 (95% CI 1.02 to 1.78) times higher in those vaccinated before first infection than in those unvaccinated at first infection.

Interpretation

The combination of natural infection and vaccination provides maximal protection against new infection with SARS-CoV-2: prior vaccination does not impair this protection.

Funding

No specific funding was received for this work.

Research in context

Evidence before this study

In a recent systematic review of cohort studies reported up to July 2021, the average reduction in COVID-19 infection rates in those with previous infection compared with those without evidence of previous infection was 90%. There is little information about the protective effect of previous infection against severe COVID-19, or about how the protective effects of previous infection against reinfection and severe disease are modified by vaccination.

What this paper adds

In unvaccinated individuals the protection against hospitalised COVID-19 conferred by previous infection is similar to that induced by vaccination. In those with previous infection, vaccination reduces the rates of reinfection and hospitalised COVID-19 by about 70%.

Implications of all the available evidence

The combination of natural infection and vaccination provides maximal protection against COVID-19: prior vaccination does not seriously impair this protection.

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  1. ScreenIT

    SciScore for 10.1101/2021.11.23.21266574: (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

    Software and Algorithms
    SentencesResources
    Linkage to health records and occupational databases: Using the Common Healthcare Identifier (CHI) held on all Scottish health records these individuals were linked to the population register, the national vaccination database, registers of teachers and health care workers, the list of those designated as clinically extremely vulnerable (eligible for shielding), the ECOSS database of test results, a database of hospitalisations (RAPID) that is updated daily, dispensed prescriptions in primary care and death registrations as described elsewhere [4–7].
    Common Healthcare
    suggested: None

    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 large cohort of test-positive individuals based on ascertainment of all detected infections in the population, the comprehensive linkage to electronic health records, and the ability to examine associations with occupation. Although reinfections with new strains were not confirmed by sequencing, the 90-day interval should be enough to exclude persistent infection except in the immunosuppressed. Restriction to those with definite previous infection – at least two positive tests or Ct < 30 – excludes those who tested positive only once before September 2020, when the Lighthouse labs began reporting Ct values. Stratification by calendar time should eliminate almost all confounding by Alpha and Delta variants, as it took only a few weeks for each of these variants to replace pre-existing strains in Scotland. The main limitation is that without regular scheduled testing, estimates of association with detected reinfection are subject to ascertainment bias. Because testing rates are lower in unvaccinated than in vaccinated individuals in this cohort, the efficacy of vaccination is likely to be underestimated by a model with calendar timescale. We have attempted to overcome this by comparing two alternative models: a conventional Cox regression with calendar timescale, and a Cox regression with tests as timescale to adjust for differential testing rates. The model with tests as timescale is eq...

    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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  2. Version published to 10.1101/2021.11.23.21266574v1 on medRxiv