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. The COVID-19 Community Research Partnership (CCRP) is a large multicenter healthcare system-based study of the COVID-19 pandemic, including factors impacting risk of infection and hospitalization. The CCRP includes a subset of immunocompromised (IC) participants with varying vaccination status over time. Methods. We conducted an observational cohort study of 2,515 IC and 41,941 non-IC CCRP participants who contributed electronic health record data and daily electronic surveys to self-report COVID-19 symptoms, test results, and vaccinations from April 2020 to March 2022. The IC population included those with stem cell transplant, HIV, cancer, autoimmune disease, or solid organ transplant. The latter 3 must have also had an active systemic therapy to meet the IC condition (e.g. chemotherapy, immune modulator, steroid). Logistic regression was used to investigate risk of COVID-19 and hospitalization among IC participants and according to vaccine status within viral variant time periods (pre-delta, delta, omicron). Results. IC conditions included cancer (51%), autoimmune (41%), solid organ/ stem cell transplant (9%), and HIV (7%). The IC group was older and had more comorbidities. 95% of vaccine recipients received an mRNA vaccine. More vaccine breakthrough infections occurred in the IC group than non-IC group (36.1% vs 29.5%, p< 0.001). IC participants were less likely to remain COVID-19 free over time if vaccinated but not boosted (Fig 1A). However, after receiving a booster there was no difference in COVID-19 cases between the groups (Fig 1B). IC participants were more likely to be hospitalized with COVID-19 (OR 2.85;95% CI 1.69-4.76), but vaccination reduced risk for hospitalization (OR 0.26;95% CI 0.08-0.8). Receipt of a booster dose reduced risk of COVID-19 among IC participants during the delta wave (IRR 0.52;95% CI 0.28-0.94) but not during omicron. However, during omicron risk of hospitalization in the IC group was reduced by a booster dose (OR 0.13;95% CI 0.02-0.72). Conclusion. IC individuals were at increased risk for COVID-19 hospitalizations and breakthrough infections. After receiving a booster, IC participants were conferred the same level of protection from infection as their non-IC counterparts, highlighting the importance of boosters for these individuals. (Figure Presented).