By the middle of March 2022, the coronavirus-19 disease (COVID-19) had infected more than 450 million people and caused nearly 6 million death worldwide (1). COVID-19 has affected almost all age groups in both previously healthy individuals and those with chronic disease including inflammatory bowel disease (IBD) (2–4). Patients with IBD particularly in the presence of systemic corticosteroids, immunosuppressive agents, or biologics are supposed to be at moderate-to-high risk who are sensitive to COVID-19 and complications (5). Vaccination is likely to be especially important in high-risk individuals like IBD patients to suppress viral dissemination and protect individual patients from COVID-19 (6).

Previous studies showed that non-live vaccines are implicated safe in patients with IBD irrespective of IBD treatment, although patients receiving certain types of immunomodulatory at the time of vaccination may have reduced vaccine immune responses (7, 8). In fact, patients with IBD are more at risk of infectious complications than the non-IBD population once infected with COVID-19 (9). Studies have demonstrated that vaccines are also protective for patients with IBD, which follows as COVID-19 vaccination is even more essential for the protection of IBD patients (10).

However, patients with IBD have more concerns about the adverse reactions and effectiveness of vaccines than ordinary people before vaccination, which leads to vaccine hesitancy (11, 12). At present, there are still many patients with IBD in China who are reluctant to receive the COVID-19 vaccine (13, 14). Therefore, we conducted a questionnaire survey of patients with IBD to understand the attitude and potential influencing factors of IBD patients to receive COVID-19 vaccine. The study will help to enhance vaccination attitude and COVID-19 vaccination coverage among patients with IBD. The study may also help gastroenterologists educate and inform their patients on the favorable of COVID-19 vaccination, and give recommendations for further vaccination (15).

The present study examined the vaccinated and non-vaccinated patients with IBD, and investigated various sociodemographic, health-related and behavioral predictors for these patients based on the HBM model. The acceptance of the COVID-19 vaccine in patients with IBD has not been adequately evaluated, and the reasons for the hesitancy of patients with IBD about the COVID-19 vaccine are unknown. A total of 288 IBD patients were finally included in this study, of which 72.6% had received the COVID-19 vaccine, which was consistent with other findings in Italy and United States (23, 24). We found that 27.4% of IBD patients were hesitant to vaccinate against COVID-19, with significantly associated factors in the adjusted analysis being disease duration, perceived benefit and cues to action.

It was reasonable to find higher intention of vaccination among respondents in the long disease duration, as their more stable condition, a better understanding of the vaccination, or a greater willingness to follow gastroenterologist advice (25). With regard to sociodemographic and health-related predictors, none were found to be significant in terms of the intention to receive COVID-19 vaccines. These included demographic considerations, such as personal status, socio-economic level and health-related factors, such as perceived health status, disease type, disease activity or having been vaccinated with other vaccines like flu vaccine in the previous year.

Previous studies have shown that inactivated vaccines such as hepatitis B vaccine, varicella vaccine and flu vaccine are well tolerated and safety (26, 27). Meanwhile, the guidelines for the vaccination of patients with autoimmune diseases or immunosuppressive therapy suggest that inactivated vaccines can benefit the patients without interruption of treatment (6, 28). In China, the COVID-19 vaccines are all inactivated vaccines, so it is feasible for patients with IBD to receive COVID-19 vaccines. In our study, the most common reasons for COVID-19 vaccine hesitancy were afraid of vaccination aggravating IBD, fear of adverse effects and worry about the current use of drugs affecting the efficacy of vaccination. These suggested that patients with IBD would be more cautious before choosing vaccination. In addition, those who were willing to be vaccinated in this study were more concerned about the effectiveness of the vaccine. While patients who refused to be vaccinated might have other immune diseases, and they were afraid that vaccination might aggravate existing conditions. These results suggested that the vaccinated group may overestimate the benefits of vaccination, while the non-vaccinated group may be unaware of the vaccine.

Whether patients with IBD should be vaccinated against COVID-19, D’Amico et al. suggested that they should receive COVID-19 vaccines, regardless of medication or comorbidities (10). According to the international consensus, it holds that no matter what drug treatment IBD patients receive, inactivated vaccines are safe for them, and vaccination is not associated with the onset or worsening of IBD (6). However, the inclusion criteria of vaccines that are currently on the market do not include patients with immune diseases or receiving immunosuppressive therapy (29, 30). Therefore, patients with IBD still need to be cautious when vaccinating against COVID-19.

In our study, multivariable analysis found that HBM constructs were associated with vaccination intention, which was in concordance with other studies (31). Especially, the findings of our study observed that a high perception of benefits and cues to action to receive the vaccine were the two most important constructs affecting a definite intention for COVID-19 vaccination. In our study, the perceived barriers against COVID-19 immunizations, especially worried about side effects had been also reported in other studies related to the introduction of a new vaccine (32). The findings implied that it should be valued the established safety and efficacy before the new vaccine made available to the public. However, perception of susceptibility was not a significant predictor in the study. While cues to actions were found to be important, namely patients would only take the COVID-19 vaccine if they were given adequate information. Therefore, it is important to provide the public with adequate information, especially strong evidence from field trials of vaccine safety and efficacy. These findings suggested that the promotion of COVID-19 vaccination in the form of advertisements and recommendations may serve as cue to action for vaccination.

There were several limitations to our study. Firstly, the present study was self-reported from patients and certainly related to the retrospective nature which might have been recalling bias and selection bias. Secondly, our study focused on the IBD patients, we just compared the factors among IBD patients and didn’t compare the factors with non-IBD controls. Thirdly, detailed characteristics of individual patients were not available. Other limitations to mention were that the survey respondents represented only a small proportion of all Chinese IBD patients and thus may not be generalizable to all Chinese IBD patients or other countries, especially considering differences in rates of both COVID-19 and IBD. The strength of our study was that we did a comprehensive survey on sociodemographic, clinical disease profile and health belief in IBD patients.

COVID-19 vaccination for the general population has been proceeding in China. Meanwhile, IBD specialists are still called upon in conducting a campaign to convince their patients to get vaccinated. Our study suggests that patients with IBD are more cautious about vaccinating against COVID-19, resulting in a higher rate of vaccine hesitancy. It is necessary to explain to patients that the benefits of vaccines outweigh the risks, especially in patients without immune disease. Further efforts should be made to protect patients with IBD from COVID-19 infections and achieve adequate vaccination coverage. Healthy education and advice from government and IBD experts may facilitate COVID-19 vaccination.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Institutional Review Board of the Ethics Committee of the Second Affiliated Hospital, School of Medicine, Zhejiang University in China (IR2021001361). The patients/participants provided their written informed consent to participate in this study.

YC, SH and JL participated in study design and study conception. SL collected the questionnaire data. SH, JL, performed statistical analysis. QW, XW, and DX performed the check of results. SH and JL drafted the manuscript. All authors provided critical review of the manuscript and approved the final draft for publication. All authors contributed to the article and approved the submitted version.