Breakthrough SARS-CoV-2 Infections after Vaccination in North Carolina
Authors: Uschner Diane , Bott Matthew , Santacatterina Michele , Gunaratne Mihili , Fette Lida M. , Burke Brian , Strylewicz Greg , Edelstein Sharon L. , Lagarde William H , Miller Kristen , Weintraub William S. , Keating Joseph , Schieffelin John , Yukich Joshua , Tapp Hazel , Ahmed Amina , Berry Andrea A. , Munawar Iqra , Seals Austin Lyles , Williamson John , Herrington David , Sanders John W. , Runyon Michael ,   for the COVID-19 Community Research Partnership
Published: October 2021

AbstractImportanceReal-world data are needed to assess incidence and factors associated with breakthrough SARS-CoV-2 infections following vaccination.ObjectiveEstimate incidence of breakthrough infections and assess associations with risk factors using self-reported data from a large NC population sample.DesignProspective observational cohort study utilizing daily online survey data to capture information about COVID-19 symptoms, testing, and vaccination status.SettingSix health care systems in North Carolina with data collected between January 15, 2021 and September 24, 2021.ParticipantsAdult study participants who reported full vaccination with a COVID-19 mRNA or J&J non-replicating viral vector vaccine (n =16,020).ExposuresPotential community exposure to SARS-CoV-2.Main Outcome and MeasuresSelf-reported breakthrough infection.ResultsSARS-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 RelevanceThis 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.Trial RegistrationThe COVID-19 Community Research Partnership is listed in clinicaltrials.gov (NCT04342884).Key PointsQuestionWhat are the characteristics of those with breakthrough infections after SARS-CoV-2 vaccination in North CarolinaãFindingsIn this NC-based observational study of 16,020 participants, 1.9% self-reported a positive SARS-CoV-2 viral test at least 2 weeks following full vaccination, reflecting an event rate of 7.3 infections per 100,000 person years. Rates were higher among younger participants, participants from more rural areas in North Carolina, and those vaccinated with J&J Ad26.COV2.S.MeaningOur results show a relatively low rate of COVID-19 infection following full vaccination. Younger adults and those vaccinated with J&J Ad26.COV2.S should be targeted for additional risk mitigation strategies.