Rick, Anne-Marie; Laurens, Matthew B; Huang, Ying; Yu, Chenchen; Martin, Thomas CS; Rodriguez, Carina A; Rostad, Christina A; Maboa, Rebone M; Baden, Lindsey R; Sahly, Hana M El; Grinsztejn, Beatriz; Gray, Glenda E; Gay, Cynthia L; Gilbert, Peter B; Janes, Holly E; Kublin, James G; Huang, Yunda; Leav, Brett; Hirsch, Ian; Struyf, Frank; Dunkle, Lisa M; Neuzil, Kathleen M; Corey, Lawrence; Goepfert, Paul A; Walsh, Stephen R; Follmann, Dean; Kotloff, Karen L; Adams, Atoya; Miller, Eric; Rankin, Bruce G; Shinn, Steven; Nash, Marshall; Green, Sinikka L; Jacobsen, Colleen; Krishnankutty, Jayasree; Phungwayo, Sikhongi; Glover, Richard M; Slechta, Stacy; Holdeman, Troy; Hartvickson, Robyn; Grant, Amber; Poling, Terry L; Klein, Terry D; Klein, Thomas C; Klein, Tracy R; Smith, William B; Gibson, Richard L; Winbigler, Jennifer; Parker, Elizabeth; Wijewardane, Priyantha N; Bravo, Eric; Thessing, Jeffrey; Maxwell, Michelle; Horn, Amanda; Healy, Catherine Mary; Akamine, Christine; Chu, Laurence; Chouteau, R Michelle; Cotugno, Michael J; Bauer, George H; Hachigian, Greg; Oshita, Masaru; Cancilla, Michael; Kiersey, Kristen; Seger, William; Antwi, Mohammed; Green, Allison; Kim, Anthony; Desjardins, Michael; Johnson, Jennifer A; Sherman, Amy; Walsh, Stephen R; Borger, Judith; Saleem, Nafisa; Solis, Joel; Medina, Martha Carmen; Keating, Westly; Garcia, Edgar; Bueno, Cynthia; Segall, Nathan; Denham, Douglas S; Weiss, Thomas; Avworo, Ayoade; Hedges, Parke; Strout, Cynthia Becher

doi:10.1016/j.ebiom.2023.104799

Download PDF

Risk of COVID-19 after natural infection or vaccination

2023

Published Web Location

https://doi.org/10.1016/j.ebiom.2023.104799

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content

For improved accessibility of PDF content, download the file to your device.

UC San Diego