Risk of COVID-19 after natural infection or vaccination
Anne-Marie Rick, Matthew B. Laurens, Ying Huang, Chenchen Yu, Thomas Martin, Carina A. Rodriguez, Christina A. Rostad, Rebone M. Maboa, Lindsey R. Baden, Hana M. El Sahly, Beatriz Grinsztejn, Glenda Gray, Cynthia L. Gay, Peter B. Gilbert, Holly Janes, James G. Kublin, Yunda Huang, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M. Dunkle, Kathleen M. Neuzil, Lawrence Corey, Paul Goepfert, Stephen R. Walsh, Dean Follmann, Karen L. Kotloff, Atoya Adams, Eric N. Miller, Bruce G. Rankin, Steven Shinn, Marshall Nash, S Green, Colleen Jacobsen, Jayasree Krishnankutty, Sikhongi Phungwayo, Richard Glover, Stacy Slechta, Troy Holdeman, Robyn Hartvickson, Amber Grant, Terry L. Poling, Terry D. Klein, Thomas Klein, Tracy Klein, William Smith, Richard Gibson, Jennifer Winbigler, Elizabeth Parker, Priyantha N. Wijewardane, Eric Bravo, Jeffrey Thessing, Michelle Maxwell, Amanda Horn, Catherine Healy, Christine Akamine, Laurence Chu, R. Michelle Chouteau, Michael J. Cotugno, George H. Bauer, Greg Hachigian, Masaru Oshita, Michael Cancilla, Kristen Kiersey, William Seger, Mohammed Antwi, Allison Green, Anthony Kim, Michaël Desjardins, Jennifer Johnson, Amy C Sherman, Stephen R. Walsh, Judith Borger, Nafisa Saleem, Joel Solis, Martha Medina, Westly Keating, Edgar García, Cynthia Bueno, Nathan Segall, Douglas Denham, Thomas Weiss, Ayoade Avworo, Parke Hedges, Cynthia Strout, Rica Santiago, Yvonne Davis, Patty Howenstine, Alison Bondell, Kristin J. Marks, Tina Wang, Timothy Wilkin, Mary Vogler, Carrie D. Johnston, Michele P. Andrasik, Jessica Andriesen, Gail Broder, Niles Eaton, Huub G. Gelderblom, Rachael McClennen
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.