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Low Rates of Breakthrough COVID-19 Infection After SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease


 We demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is highly effective at preventing coronavirus disease 2019 (COVID-19). Immunosuppressive medications, commonly used to treat patients with inflammatory bowel disease (IBD), may diminish vaccine response, predisposing to breakthrough infection. Prior studies of patients with IBD found low short-term (within 30 days of vaccination) rates of breakthrough infection, with a majority occurring before receipt of second messenger RNA (mRNA) vaccine dose. [1][2][3] However, longer-term data are needed to better understand vaccine effectiveness and durability in this vulnerable population. We aimed to describe the incidence and severity of, and risk factors for, COVID-19 infection in the 6 months following SARS-CoV-2 vaccination in a large, geographically diverse population of patients with IBD.
The PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) trial is a prospective, observational Participants included in this analysis completed SARS-CoV-2 vaccination and the 6-month follow-up survey prior to December 7, 2021. We used descriptive statistics to characterize the study population and bivariate statistics to evaluate associations between patient characteristics and COVID-19 infection ≥1 month after receipt of the Ad26.COV2.S vaccine or second dose of an mRNA vaccine. Variables included prior COVID-19 infection, age, sex, disease type (Crohn's disease vs ulcerative colitis vs IBD-unspecified or missing), vaccine type, IBD medication at time of initial vaccination, geographical region of residence, and anti-RBD antibody level where applicable.
Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA). P values <.05 were considered significant. The study was approved by the University of North Carolina at Chapel Hill Institutional Review Board.
Individuals in the South were more likely to develop COVID-19 infection following vaccination compared with those in other regions (P = .028). Although not statistically significant, the AD26.COV2.S vaccine was numerically less effective at preventing infection compared with mRNA vaccines. Age, sex, and IBD medication class at time of initial vaccination were not associated with breakthrough infections (Table 1).
Of 2006 participants who underwent anti-RBD antibody measurement, median antibody levels were lower in individuals who developed breakthrough infection compared with those who did not (median 7.1 µg/mL vs 17.0 µg/mL; P = .004).
Our findings demonstrate low rates of breakthrough COVID-19 infection and a relatively mild course of illness after completion of SARS-CoV-2 vaccination in a large U.S. IBD cohort. These data correlate well with real-world surveillance data from Israel, where vaccine effectiveness within 4 months of receiving 2 doses of BNT162b2 was estimated to be 95.3%. 6 Similarly, 6-month postimmunization follow-up data from the BNT162b2 multinational phase 1-2-3 clinical trial found that 2 doses of BNT162b2 were 91.1% effective at preventing COVID-19 infection and 97% effective at preventing severe disease from 7 days to 6 months after second vaccine dose. 7 As in the initial clinical trials of the SARS-CoV-2 vaccines, these real-world data in patients with IBD reaffirm that vaccination was highly effective at preventing severe disease and death, even among patients on immunosuppression. In our cohort, lower anti-RBD antibody levels following primary vaccine series were associated with breakthrough infections. Additionally, lower vaccination rates in the southern United States and the emergence of delta as the predominant COVID-19 variant by summer 2021 may have contributed to increased breakthrough infections in this group. It is also possible that waning immunity among those vaccinated >6 months prior played a role in breakthrough cases as was seen in a large Israeli study. 8 Interestingly, only 9 participants were treated with monoclonal antibodies, which are indicated for nonhospitalized patients with mild-moderate COVID-19 infection at high risk of developing severe disease. Educating patients and providers about emerging COVID-19 treatments is essential.
Study strengths include the large population size and geographic diversity, the length of follow-up to assess breakthrough infections, and the robust retention rate (>90%). We also captured participant reports of home-and clinic-based tests.
Limitations include a convenience sample that may impact external validity and reliance on patient self-report for demographic or disease characteristics and COVID-19 infection. Additionally, objective markers of IBD activity were not available in this population. As most participants who reported COVID-19 infection were symptomatic, it is possible that the rate of breakthrough infection is underestimated, as surveillance testing of asymptomatic individuals was not performed as part of our protocol. Lack of a non-IBD comparison group and the limited length of follow-up in this report are additional limitations, although longer-term follow-up is ongoing in this cohort.
Longer-term follow-up is ongoing to (1) evaluate the impact of additional vaccine or booster doses as well as omicron and other emerging variants on rates of breakthrough COVID-19 infection, (2) correlate levels of quantitative antibodies with breakthrough infections, and (3) further elucidate risk factors for breakthrough infection including vaccine type and other patient and treatment characteristics.