Duration of Protection Against SARS-CoV-2 Reinfection and Associated Risk of Reinfection Assessed with Real-World Data

  1. Shannon L. Reynolds
  2. Harvey W. Kaufman
  3. William A. Meyer
  4. Chris Bush
  5. Oren Cohen
  6. Kathy Cronin
  7. Carly Kabelac
  8. Sandy Leonard
  9. Steve Anderson
  10. Valentina Petkov
  11. Douglas Lowy
  12. Norman Sharpless
  13. Lynne Penberthy

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Abstract

Importance

Better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection is needed.

Objective

Primary: To assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection. Secondary: Evaluate the crude SARS-CoV-2 reinfection rate and associated characteristics.

Design and Setting

Retrospective observational study of HealthVerity data among 144,678,382 individuals, during the pandemic era through April 2021.

Participants

Individuals studied had SARS-CoV-2 molecular diagnostic or antibody index test results from February 29 through December 9, 2020, with ≥365 days of pre-index continuous closed medical enrollment, claims, or electronic health record activity.

Main Outcome(s) and Measure(s)

Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result.

Results

Among 22,786,982 individuals with index SARS-CoV-2 laboratory test data (2,023,341 index positive), the crude rate of reinfection during follow-up was significantly lower (9.89/1,000-person years) than that of primary infection (78.39/1,000 person years). Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals (hazard ratio, 0.13; 95% CI, 0.13, 0.13). The cumulative incidence of reinfection among index-positive individuals and infection among index-negative individuals was 0.85% (95% CI: 0.82%, 0.88%) and 6.2% (95% CI: 6.1%, 6.3%), respectively, over follow-up of 375 days. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk.

Conclusions and Relevance

This large US population-based study demonstrates that SARS-CoV-2 reinfection is uncommon among individuals with laboratory evidence of a previous infection. Protection from SARS-CoV-2 reinfection is stable up to one year. Reinfection risk was primarily associated with age 85+ years, comorbid immunologic conditions and living in congregate care settings; healthcare workers demonstrated a decreased reinfection risk. These findings suggest that infection induced immunity is durable for variants circulating prior to Delta.

Key Points

Question

How long does prior SARS-CoV-2 infection provide protection against SARS-CoV-2 reinfection?

Finding

Among >22 million individuals tested February 2020 through April 2021, the relative risk of reinfection among those with prior infection was 87% lower than the risk of infection among individuals without prior infection. This protection was durable for up to a year. Factors associated with increased likelihood of reinfection included older age (85+ years), comorbid immunologic conditions, and living in congregate care settings; healthcare workers had lower risk.

Meaning

Prior SARS-CoV-2 infection provides a durable, high relative degree of protection against reinfection.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2022.02.25.22271515: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was deemed exempt by the New England Institutional Review Board (#1-9757-1).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Study Design: Study Population: The dataset included records for individuals with an index NAAT or SARS-CoV-2 antibody test from February 29, 2020 (when SARS-CoV-2 NAAT first became available for molecular diagnostic testing), through December 9, 2020 (prior to COVID-19 vaccine introduction).
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Exposure, Outcome and Covariates: For the primary objective, individuals entered the cohort upon their first SARS-CoV-2 NAAT or antibody test; those with a positive result were classified as the index-positive group (i.e., established SARS-CoV-2 infection) while individuals whose first NAAT or antibody test result was negative were the index-negative group (i.e., without laboratory evidence of SARS-CoV-2 infection).
    Covariates
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.02.25.22271515 on medRxiv