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Risk of COVID-19 after natural infection or vaccination

  • the NIAID-funded COVID-19 Prevention Network (CoVPN)
    • University of Pittsburgh
    • University of Maryland, Baltimore
    • Fred Hutchinson Cancer Research Center
    • University of California at San Diego
    • University of South Florida
    • Children's Healthcare of Atlanta
    • Ndlovu Research Centre
    • Harvard University
    • Baylor College of Medicine
    • Fundação Oswaldo Cruz
    • South African Medical Research Council
    • University of North Carolina at Chapel Hill
    • Moderna Therapeutics
    • AstraZeneca
    • Johnson & Johnson
    • Novavax, Inc.
    • University of Alabama at Birmingham
    • National Institutes of Health

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

    Original languageEnglish
    Article number104799
    JournalEBioMedicine
    Volume96
    DOIs
    Publication statusPublished - Oct 2023

    UN SDGs

    This output contributes to the following UN Sustainable Development Goals (SDGs)

    1. SDG 3 - Good Health and Well-being
      SDG 3 Good Health and Well-being

    Keywords

    • COVID-19
    • Hybrid immunity
    • Natural infection
    • Vaccination

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology

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