Abstract

Importance: Real-world data are needed to assess incidence and factors associated with breakthrough SARS-CoV-2 infections following vaccination. Objective: Estimate incidence of breakthrough infections and assess associations with risk factors using self-reported data from a large NC population sample. Design: Prospective observational cohort study utilizing daily online survey data to capture information about COVID-19 symptoms, testing, and vaccination status. Setting: Six health care systems in North Carolina with data collected between January 15, 2021 and September 24, 2021. Participants: Adult study participants who reported full vaccination with a COVID-19 mRNA or J&J non-replicating viral vector vaccine (n = 16,020). Exposures: Potential community exposure to SARS-CoV-2. Main Outcome and Measures: Self-reported breakthrough infection. Results: SARS-CoV-2 infection after vaccination was self-reported in 1.9% of participants, with an incidence rate of 7.3 per 100,000 person-years. Younger age (45-64 vs. 18-44: HR (95% CI) = 0.65 (0.51-0.82); 65+ vs. 18-44: HR (95% CI) = 0.59 (0.39-0.90)), and vaccination with J&J Ad26.COV2.S were associated with a higher risk of breakthrough infection compared to vaccination with Pfizer BNT162b2 (Ad26.COV2.S vs. BNT162b2: HR (95% CI) = 2.23 (1.40-3.56)), while participants vaccinated with mRNA-1273 (mRNA-1273 vs. BNT162b2: HR (95% CI) = 0.69 (0.50-0.96) and those residing in urban counties experienced a lower rate of SARS-CoV-2 breakthrough infection compared with those from suburban (HR (95% CI) = 1.39 (1.01-1.90)) or rural (HR (95% CI) = 1.57 (1.16-2.11)) counties. There was no significant association between breakthrough infection and participant sex, race, healthcare worker status, prior COVID-19 infection, routine mask use, or overall vaccination rate in the county of residence. Conclusions and Relevance: This NC community-based observational study showed that the proportion of the cohort who self-report breakthrough SARS-CoV-2 infections was 7.3 events per 100,000 person-years. Younger adults, those vaccinated with J&J Ad26.COV2.S, and those residing in suburban or rural counties were at higher risk of breakthrough infections and should be targeted for additional risk mitigation strategies to decrease community transmission.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The study was funded by the CARES Act of the U.S. Department of Health and Human Services (HHS) [Contract # NC DHHS GTS #49927]

Author Declarations

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Institutional Review Board of the Wake Forest School of Medicine gave ethical approval for this work.

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Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv