COVID-19 Vaccination Among Individuals With Inflammatory Bowel Disease: Perception, Efficacy, and Safety

The COVID-19 pandemic, caused by SARS-CoV-2, has been the most significant global health crisis of the past century. The development of safe and effective vaccines has led to a reduction in COVID- 19-related hospitalizations and deaths;however, the clinical trials that led to US Food and Drug Administration Emergency Use Authorization and/or approval of the vaccines in the United States did not include individuals with inflammatory bowel disease (IBD). Because individuals with IBD are commonly treated with immunosuppressive medications, there had been concern for reduced vaccine efficacy in this population. This article provides an overview of the peer-reviewed literature addressing COVID-19 vaccination in individuals with IBD;details the perceptions of patients with IBD of COVID-19 vaccines, including how gastroenterologists can help to reduce vaccine hesitancy;and describes the humoral immune response to COVID-19 vaccines, with a majority of patients with IBD seroconverting following complete vaccination regardless of medication exposure. Additionally, low rates of IBD flare and similar rates of vaccine-related adverse events to those in the general population are described. Finally, the article provides current recommendations from the Centers for Disease Control and Prevention for COVID-19 vaccination in individuals with IBD.

SYSTEMIC CORTICOSTEROIDS BUT NOT ANTI-TNF ARE ASSOCIATED WITH INCREASED RISK OF HOSPITALIZATION, INTENSIVE CARE, AND DEATH AMONG PATIENTS WITH IBD: RESULTS FROM A LARGE, POPULATION-BASED COHORT

Introduction: Immunosuppressed individuals are at higher risk for COVID-19 and resulting complications, yet robust data in patients with Inflammatory Bowel Disease (IBD) are lacking. We evaluated the risk of COVID-19-related hospitalization and severe sequelae in a large, population-based U.S. cohort of patients with IBD. Methods: We conducted a retrospective cohort study utilizing insurance claims data from two large U.S. health plans (Anthem and Humana). Cohort follow-up began on 1 March 2020, the beginning of the COVID-19 pandemic in the US. We included IBD patients identified by two diagnosis codes for Crohn's disease (CD) or ulcerative colitis (UC) or one diagnosis code plus a treatment code for an IBD-specific medication in the six months prior to cohort entry. Use of IBD medications was ascertained in the 90 days prior to cohort entry. Study outcomes included COVID-19 hospitalization, mechanical ventilation, and inpatient death. Patients were followed until outcome of interest, death, disenrollment, or end of the study period. We described the occurrence of COVID-19 outcomes according to IBD treatment status ascertained prior to cohort entry. Results: The study population included 102,989 patients (48,728 CD, 47,592 UC) with a mean age of 53 years;55% were female. Overall, 412 (0.4%) patients were hospitalized for COVID-19. Individuals treated with systemic corticosteroids were more likely to be hospitalized than those treated with any other non-steroid medication (0.6% vs 0.3%, p=<.0001). Among patients not treated with corticosteroids, patients receiving anti-TNF were less likely to be hospitalized than those treated with other medication classes (0.2% vs 0.5%, p=<.0001) or no medications (0.5%, p=<.0001). Older age was associated with increased incidence of hospitalization for COVID-19. Overall, 71 patients (0.07%) required mechanical ventilation and 52 (0.05%) died at the hospital due to COVID-19 or resulting complications. The proportion of patients requiring mechanical ventilation or dying was higher amongst users of corticosteroids versus those treated with any other non-steroid medication (1.9% vs 0.05%, p=<.0001 and 0.1% vs 0.04%, p=0.0015) respectively). Associations between corticosteroid use all outcomes were similar across age groups. Conclusion: Among patients with IBD, those treated with systemic corticosteroids had more frequent hospitalization, mechanical ventilation, and death from COVID-19 as compared to patients on other treatments or no treatment at all. Anti-TNF therapy was associated with a decreased occurrence of hospitalization. This finding reinforces previous guidance to taper and/or discontinue corticosteroids to reduce the risk of infections, including COVID-19. Use of steroid-sparing maintenance treatments such as anti-TNF agents appears to be safe.

STRONG HUMORAL IMMUNE RESPONSE TO SARS-COV-2 VACCINE ADDITIONAL DOSE AMONG PATIENTS WITH INFLAMMATORY BOWEL DISEASES

Background: Current recommendations in many countries support additional COVID-19 vaccine doses in patients with inflammatory bowel disease (IBD) who are treated with immunosuppressants, yet real-world data on the effectiveness and safety of additional vaccine doses is lacking. We sought to quantify the humoral immune response to an additional (third) dose of mRNA vaccines in adolescents and adult patients with IBD. Methods: We performed a direct-to-patient, internet-based cohort study of patients with IBD in the United States who have received any SARS-CoV-2 vaccine granted EUA. Participants completed baseline and follow-up surveys and had blood work obtained approximately 8 weeks following completion of the initial vaccination series and 6 weeks following administration of an additional (third) vaccine dose. We performed quantitative measurement of antireceptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 using the LabCorp Cov2Quant IgG™ assay. Results: A total of 659 participants were included [415 participants (63%) initially received BNT162b2, 243 participants (37%) initially received mRNA-1273, and 5 participants (1%) initially received Ad26.COV2.S]. Demographic, clinical, and treatment characteristics of the study population are provided in Table 1. Over 98% of those receiving an initial mRNA vaccine received the same type additional dose. Whereas 93% had detectable antibody after the initial vaccination series, 99.5% had detectable antibodies following an additional dose. Mean (SD) increase in antibody level was 61 ug/mL (103) in those receiving BNT162b2 and 78 ug/mL (143) for those receiving mRNA-1273 (Figure 1). Importantly, of 47 of patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose. Additional vaccination was generally well tolerated in this population, with 44%, 24%, 25%, and 6% reporting no, mild, moderate, and severe side effects respectively. Discussion: These findings demonstrate robust immunogenicity to additional doses of SARS-CoV-2 vaccine, even amongst patients with undetectable antibody following the initial series. Adverse event rates were low. These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression. (Table Presented) (Figure Presented)

CROSS-SECTIONAL AND LONGITUDINAL ASCERTAINMENT OF PATIENTS WITH IBD'S PERCEPTIONS AND EXPERIENCES DURING COVID-19: CLAPPED COVID-19

Background - Patients with Inflammatory Bowel Disease (IBD) require long-term followup and potentially immunosuppressive medications. We sought to assess these patients' experiences during the COVID-19 pandemic as well as the pandemic's impact on patients' access to and behavior around seeking clinical care. We hypothesized that the COVID-19 pandemic had a significant impact on how patients with IBD seek and prefer to obtain health care. Methods - We conducted a repeated cross-sectional survey within the IBDPARTNERS Internet-based cohort from April 2020 to June 2021. Follow-up surveys occurred at weeks 2, 4, 6, 8, 26, and 52. Surveys included questions about residence, demographics, experience with telemedicine, COVID vaccination status, health care behavioral changes, and medication changes throughout the pandemic. Statistical Analysis - Descriptive statistics were used to summarize the cohort. Ordered logistic regression was used to examine the associations between baseline characteristics and levels of concern regarding the pandemic. Logistic regression was used to examine the relationships between levels of concern and changing patient behaviors. Due to the repeated longitudinal nature of the data and potential intra-subject correlation, all regression analysis was done on panel data. Results - A total of 2,121 patients (Table 1) completed the baseline survey with a response rate of >90% for each follow-up survey. The general level of concern regarding the pandemic and the level of concern regarding IBD medications during the pandemic decreased significantly over the survey period (Figures 1A-1B). Older age, female sex, higher education, higher Patient- Reported Outcomes Measurement Information System (PROMIS) scores, presence of non- IBD comorbidities, and COVID vaccination were significantly associated with levels of general concern regarding COVID (Figure 1C). The overall perception of telemedicine was positive (Figure 1D), although preferences for telemedicine or in-person visit varied based on the type of care (routine visit, IBD medication change, addressing IBD flare, etc.) needed. While news media and the CDC remained the most common sources of coronavirus information, patient websites such as Crohn's and Colitis Foundation increased slightly over the study period. Conclusion - During the study period (April 2020 - June 2021), the general and IBD-specific levels of concern among adults with IBD decreased significantly. Preferences for telemedicine or in-person care varied based on the reasons for seeking care. These data give clinically relevant insights that can inform immediate and future adjustments regarding patient care, such as investing in the development of telemedicine and improving the accessibility of patient websites, as we move the practice of gastroenterology into the post- COVID-19 era. (Table Presented) (Figure Presented) Figure 1. Each of the panel figures (1A-1D) highlights a major finding of the study.

Humoral immune response after completion of covid-19 vaccine series among patients with ibd

Introduction: Individuals on immunosuppression were excluded from COVID-19 vaccine clinical trials which led to their emergency use authorization (EUA). As a result, patients with inflammatory bowel disease (IBD) who are frequently treated with immune suppressing medications have questions about COVID-19 vaccine effectiveness. Data of vaccine effectiveness and immune response in the IBD population are urgently needed to guide vaccination strategies. This study aimed to assess serologic response after completion of COVID-19 vaccine series in a large IBD population across the US. Methods: Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID (PREVENT-COVID) is a prospective observational cohort study of IBD patients who received any COVID-19 vaccine granted EUA in the US. Enrolled participants had the option to provide serum samples to evaluate antibody development 8 weeks following completion of COVID-19 vaccine series. Quantitative analysis of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 was performed using the LabCorp Cov2Quant IgG assay. Qualitative assessment of nucleocapsid antibodies as an indicator of past infection was also completed. This analysis included participants who completed vaccination series and laboratory testing prior to 6/17/ 21. Individuals who reported prior COVID infection and/or had positive nucleocapsid antibody were excluded. Descriptive statistics were performed to characterize the study population and antibody response. Results: A total of 788 participants with IBD (mean age 48 yrs, 73% female) were included, and 752/ 788 [95.4%, 95% confidence interval (CI) 93.7-96.7%] had detectable anti-RBD antibodies. Additional demographic characteristics and distribution of antibody response across medication classes are shown in Table 1. Antibody response was generally similar across age group, vaccine type, and IBD medication class (Figure 1);however, individuals receiving corticosteroids (n=35) had reduced antibody response with 85.7% (95% CI 70.6-93.7) having detectable antibodies vs 95.9% (95% CI 94.2-97.1) in non-steroid users. Conclusion: A vast majority of our IBD cohort including those on immunosuppressive therapies demonstrated humoral immune response after completion of COVID-19 vaccine series. Longer term data are needed to assess durability of antibody response, but this emerging data provides reassurance that most IBD medications do not significantly diminish response to COVID-19 vaccination.