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Association of Prior SARS-CoV-2 Infection With Risk of Breakthrough Infection Following mRNA Vaccination in Qatar

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Key Points

Question  Are persons vaccinated after SARS-CoV-2 infection better protected against breakthrough infection than those vaccinated without prior infection?

Findings  In this cohort study of 1 531 736 mRNA-vaccinated individuals in Qatar, prior SARS-CoV-2 infection was associated with a statistically significant reduced hazard of breakthrough infection among recipients of both the BNT162b2 (Pfizer-BioNTech) (adjusted hazard ratio, 0.62) and the mRNA-1273 (Moderna) vaccines (adjusted hazard ratio, 0.40).

Meaning  Prior SARS-CoV-2 infection was associated with a lower risk for breakthrough infection among persons receiving the SARS-CoV-2 mRNA vaccines; however, the observational study design precludes direct comparison of infection risk between the 2 vaccines.

Abstract

Importance  The effect of prior SARS-CoV-2 infection on vaccine protection remains poorly understood.

Objective  To assess protection from SARS-CoV-2 breakthrough infection after mRNA vaccination among persons with vs without prior SARS-CoV-2 infection.

Design, Setting, and Participants  Matched-cohort studies in Qatar for the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines. A total of 1 531 736 individuals vaccinated with either vaccine between December 21, 2020, and September 19, 2021, were followed up beginning 14 days after receiving the second dose until September 19, 2021.

Exposures  Prior SARS-CoV-2 infection and COVID-19 vaccination.

Main Outcomes and Measures  Incident SARS-CoV-2 infection, defined as a polymerase chain reaction (PCR)–positive nasopharyngeal swab regardless of reason for PCR testing or presence of symptoms. Cumulative incidence was calculated using the Kaplan-Meier estimator method.

Results  The BNT162b2-vaccinated cohort comprised 99 226 individuals with and 290 432 matched individuals without prior PCR-confirmed infection (median age, 37 years; 68% male). The mRNA-1273–vaccinated cohort comprised 58 096 individuals with and 169 514 matched individuals without prior PCR-confirmed infection (median age, 36 years; 73% male). Among BNT162b2-vaccinated persons, 159 reinfections occurred in those with and 2509 in those without prior infection 14 days or more after dose 2. Among mRNA-1273–vaccinated persons, 43 reinfections occurred in those with and 368 infections in those without prior infection. Cumulative infection incidence among BNT162b2-vaccinated individuals was an estimated 0.15% (95% CI, 0.12%-0.18%) in those with and 0.83% (95% CI, 0.79%-0.87%) in those without prior infection at 120 days of follow-up (adjusted hazard ratio for breakthrough infection with prior infection, 0.18 [95% CI, 0.15-0.21]; P < .001). Cumulative infection incidence among mRNA-1273–vaccinated individuals was an estimated 0.11% (95% CI, 0.08%-0.15%) in those with and 0.35% (95% CI, 0.32%-0.40%) in those without prior infection at 120 days of follow-up (adjusted hazard ratio, 0.35 [95% CI, 0.25-0.48]; P < .001). Vaccinated individuals with prior infection 6 months or more before dose 1 had statistically significantly lower risk for breakthrough infection than those infected less than 6 months before dose 1 (adjusted hazard ratio, 0.62 [95% CI, 0.42-0.92]; P = .02 for BNT162b2 and 0.40 [95% CI, 0.18-0.91]; P = .03 for mRNA-1273 vaccination).

Conclusions and Relevance  Prior SARS-CoV-2 infection was associated with a statistically significantly lower risk for breakthrough infection among individuals receiving the BNT162b2 or mRNA-1273 vaccines in Qatar between December 21, 2020, and September 19, 2021. The observational study design precludes direct comparisons of infection risk between the 2 vaccines.

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Article Information

Corresponding Author: Laith J. Abu-Raddad, PhD, Weill Cornell Medicine–Qatar, Qatar Foundation–Education City, Doha 24144, Qatar (lja2002@qatar-med.cornell.edu).

Accepted for Publication: October 15, 2021.

Published Online: November 1, 2021. doi:10.1001/jama.2021.19623

Correction: This article was corrected online November 22, 2021, to fix an incorrect word in the Results section of the Abstract.

Author Contributions: Dr Abu-Raddad and Ms Chemaitelly had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Abu-Raddad, Chemaitelly, E. Al Kuwari, Nasrallah, M. G. Al Kuwari, Al Romaihi, Al-Thani, Al Khal, Bertollini.

Acquisition, analysis, or interpretation of data: Abu-Raddad, Chemaitelly, Ayoub, Yassine, Benslimane, Al Khatib, Tang, Hasan, Coyle, Al Kanaani, Jeremijenko, Kaleeckal, Latif, Shaik, Abdul Rahim, Butt, Bertollini.

Drafting of the manuscript: Abu-Raddad, Chemaitelly, Ayoub, Tang, Kaleeckal.

Critical revision of the manuscript for important intellectual content: Abu-Raddad, Chemaitelly, Ayoub, Yassine, Benslimane, Al Khatib, Tang, Hasan, Coyle, Al Kanaani, E. Al Kuwari, Jeremijenko, Latif, Shaik, Abdul Rahim, Nasrallah, M. G. Al Kuwari, Butt, Al Romaihi, Al-Thani, Al Khal, Bertollini.

Statistical analysis: Abu-Raddad, Chemaitelly.

Obtained funding: Abu-Raddad, Tang.

Administrative, technical, or material support: Abu-Raddad, Ayoub, Al Khatib, Tang, Hasan, Kaleeckal, Shaik, Abdul Rahim, Nasrallah, M. G. Al Kuwari, Butt, Al-Thani, Al Romaihi, Al Khal.

Supervision: Abu-Raddad, Yassine, Tang, Bertollini.

Conflict of Interest Disclosures: Dr Butt reported receiving institutional grant funding from Gilead Sciences unrelated to the current study. No other disclosures were reported.

Funding/Support: Qatar Genome Programme provided funding for the viral genome sequencing. Support was provided by the Biomedical Research Program; the Biostatistics, Epidemiology, and Biomathematics Research Core; and the Genomics Core, all at Weill Cornell Medicine–Qatar, as well as from the Ministry of Public Health and Hamad Medical Corporation to facilitate the conduct of this study.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: Statements made herein are solely the responsibility of the authors.

Additional Contributions: We acknowledge the many individuals at Hamad Medical Corporation, the Qatar Ministry of Public Health, the Primary Health Care Corporation, Sidra Medicine, and the Qatar Biobank for their efforts and contributions to make this study possible.

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