ABSTRACT
Background. We characterize the incidence and risk factors of SARS-CoV-2 breakthrough infections in the NC-CCRP. Cumulative Incidence of Breakthrough infections after Self-reported Symptomatic SARS-CoV-2 Test Cumulative incidence curves (1 minus the unadjusted Kaplan-Meier risk), number at risk at each time point for the first self-reported symptomatic positive SARS-CoV-2 test, starting from full vaccination among participants who reported full vaccination. Methods. The NC-CCRP is an observational cohort study assessing COVID-19 symptoms, test results, vaccination status, and risk behavior via daily email or text surveys. Cox models were used to estimate hazard rates. Fixed covariates were age at enrollment, race/ethnicity, sex, county of residence classification, vaccine product, and healthcare worker status. Time varying covariates were vaccination rate in county of residence, mask usage in the week prior, the Delta time frame, the Omicron time frame, and receipt of a vaccine booster. Results. Among 15,808 eligible adult participants, 638 (4.0%) reported a positive SARS-CoV-2 test after vaccination from 01/15/2021 to 01/03/2022. The breakthrough rate increased with time from vaccination (Figure), with a cumulative incidence of 6.95% over 45 weeks of follow-up. Factors associated with a lower risk of breakthrough infection (p< 0.05) included older age (HR 0.7 for participants 45-64 years and 0.41 for those > 65 years compared to those 18-44 years), prior SARS-CoV-2 infection (HR 0.58), higher rates of mask use (HR 0.66), and receipt of a booster vaccination (HR 0.33). Higher rates of breakthrough infection were reported by participants vaccinated with BNT162b2 (HR 1.35) or Ad26.COV2.S (1.74) compared to mRNA-1273, those residing in suburban (HR 1.33) or rural (1.24) counties compared to urban counties, and during circulation of the Delta (3.54) and Omicron (16.68) variants compared to earlier time periods. There was no association of breakthrough infection with sex, race/ethnicity, healthcare worker status, or vaccination rate in the county of residence. Conclusion. In this real-world analysis, risk of breakthrough infections increased with time since vaccination, with some variability among the specific vaccine products. Risk increased dramatically during the Omicron surge. Higher rates among younger individuals may reflect more frequent, or higher risk exposures, including those related to childcare. Significantly lower rates of breakthrough associated with mask wearing and receipt of a booster highlight specific measures that individuals can take to minimize the risk for COVID-19.
ABSTRACT
Background. Wearing a face mask is a primary public health method to reduce SARS-CoV-2 transmission. We assessed the association between self-reported mask use and risk of COVID-19 infection during three periods of the pandemic. Methods. We performed a nested case-control analysis within the NC-CCRP of adults >=18 years who completed daily syndromic surveillance surveys from April 2020 through February 2022, comparing self-reported cases to controls who never selfreported a positive test. We matched up to 10 controls to each case on calendar time of self-reported positive test and corresponding daily survey entry. Not wearing a mask was defined as responding "no" at least once in the ten days preceding the match date to "In the last 24 hours, have you worn a face mask or face covering every time you interacted with others (not in your household) within a distance of less than 6 feet?" Conditional logistic regression models of risk of COVID-19 infection were adjusted for demographics, vaccination status, and recent known exposure to COVID-19. We tested any days not wearing a mask during the Pre-Delta (July 1 2020-June 30, 2021), Delta (July 1- November 30, 2021), and Omicron (December 1, 2021 - February 28, 2022) periods. Results. Among 3,901 cases and 27,813 date-matched controls, there was a significant interaction between mask use and time period (p< 0.001). Prior to July 2021, the odds of a reported SARS-CoV-2 infection was 66% higher (aOR=1.66, 95% CI=1.43 - 1.91) among participants reporting at least one day not wearing a mask compared to those who reported no days (1592 cases, 11717 controls). During the Delta-predominant period, the results were similar (aOR=1.53, 95% CI=1.23 - 1.89;659 cases, 4649 controls). This association was attenuated during the Omicron-predominant period, where the odds of a reported SARS-CoV-2 infection was 16% higher (aOR=1.16, 95% CI=1.03 - 1.32;1563 cases, 10960 controls). Conclusion. While the effect of not wearing a mask remains significant, during the Omicron-predominant period we observed a decrease in the association between self-reported mask wearing and risk of SARS-CoV-2 infection. The increased transmissibility of Omicron, pandemic fatigue, and increasing population immunity are possible contributing factors.