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Letter to the Editor Update on SARS-CoV-2 vaccination of patients with inflammatory bowel disease: what clinicians need to know
Yoo Jin Lee1,*orcid, Seong-Eun Kim2,*orcid, Yong Eun Park3orcid, Ji Young Chang4orcid, Hyun Joo Song5orcid, Duk Hwan Kim6orcid, Young Joo Yang7orcid, Byung Chang Kim8orcid, Jae Gon Lee9orcid, Hee Chan Yang10orcid, Seung-Jae Myung11,orcid, Clinical Practice Guideline Committee of the Korean Association for the Study of Intestinal Diseases
Intestinal Research 2022;20(3):386-388.
DOI: https://doi.org/10.5217/ir.2020.00172
Published online: March 11, 2022

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea

2Division of Gastroenterology, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea

3Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea

4Department of Health Promotion Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Korea

5Division of Gastroenterology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju, Korea

6Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, Korea

7Division of Gastroenterology, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea

8Center for Colorectal Cancer, National Cancer Center, Goyang, Korea

9Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea

10Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea

11Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to Seung-Jae Myung, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Tel: +82-2-3010-3917, Fax: +82-2-476-0824, E-mail: sjmyung@amc.seoul.kr
*These authors contributed equally to this work as first authors.
• Received: December 22, 2021   • Revised: January 19, 2022   • Accepted: January 21, 2022

© Copyright 2022. Korean Association for the Study of Intestinal Diseases.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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As evidences for coronavirus disease 2019 (COVID-19) is expanding, the management strategies for patients with inflammatory bowel disease (IBD) is rapidly evolving [1,2]. Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the principal strategy to curb the ongoing pandemic, in particular to prevent severe COVID-19 cases. As the initial clinical trials of the current SARS-CoV-2 vaccines did not include people with immune-mediated diseases, clinicians remain concerned about the safety and efficacy of SARS-CoV-2 vaccination in patients with IBD and about the possible effects of treatment on vaccine efficacy. An expert consensus statement by the Korean Association for the Study of Intestinal Diseases (KASID) on SARS-CoV-2 vaccination for adult IBD patients has been published [3]. As evidence is constantly gathered, resulting in changes to vaccination policies, the purpose of this letter is to update SARS-CoV-2 vaccination information on patients with IBD.
Currently, several studies are evaluating the effectiveness of SARS-CoV-2 vaccination in patients with IBD. A recent meta-analysis found that the pooled seroconversion rate after 2 doses of an mRNA vaccine in IBD patients was 95.17%, thus no lower than that in patients with other immune-mediated inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, and vasculitis [4]. The most recent data indicate that vaccinated IBD patients are well-protected against severe COVID-19 infection or death [5,6]. Thus, it is strongly recommended that unvaccinated IBD patients should be vaccinated as soon as possible.
The evidence suggests that IBD patients receiving immunemodifying therapies may exhibit attenuated immune responses after vaccination, and protection against SARS-CoV-2 infection may wane over time. In a large-scale IBD cohort study performed in the UK (CLARITY-IBD), patients on infliximab evidenced 4- to 6-fold lower antibody levels than those of vedolizumab-treated patients [7]. At 14 to 18 weeks after the second dose, the level of vaccine-induced antibodies in infliximab-treated patients decreased below the level thought necessary to afford immunity; this was not apparent in those on vedolizumab or in healthy controls [5]. Only a few corticosteroid data are available; however, patients on corticosteroids also exhibited impaired seroconversion after 2 doses of an mRNA vaccine [4]. Such findings have prompted discussion on the need for additional vaccination of IBD patients receiving immune-modifying therapies.
The Joint Committee on Vaccination and Immunisation (JCVI) of the UK developed guidelines for delivery of a third dose of an mRNA SARS-CoV-2 vaccine to moderate-to-severely immunocompromised persons and those on immune-suppressive medications [8]. As the COVID-19 situation worsened and evidence supporting a third dose accumulated, the target populations, and the interval between the primary vaccination series and the third dose, have changed several times. Also, the recommendations differ somewhat by country. The Korea Disease Control and Prevention Agency (KDCA) decided that immunocompromised individuals would receive their third dose commencing in October 2021. With the latest information, on 13 December 2021, the KDCA recommended a third dose for all individuals aged ≥ 18 years to be delivered at least 3 months (3–6 months) after the second dose. However, in immunocompromised individuals and those who received the Janssen vaccine, the third dose can be given 2 months after the second dose [9]. In terms of IBD patients, those taking high-dose corticosteroids (equivalent to ≥ 20 mg prednisolone per day) for > 10–14 days, tumor necrosis factor, interleukin 12/23, or Janus kinase inhibitors are eligible for the third dose 2 months after the second dose [8,10]. Unlike the KDCA, the JCVI described eligible patients on non-biological, oral immunomodulators in more detail, as follows: methotrexate > 20 mg/wk (oral and subcutaneous), azathioprine > 3.0 mg/kg/day, or 6-mercaptopurine > 1.5 mg/kg/day, or mycophenolate > 1 g/day over the previous 3 months [8].
The effectiveness of the third vaccine dose in patients with IBD remains unclear. However, given the risk of a blunted immune response in immunocompromised individuals following 2 vaccine doses, and the emerging SARS-CoV-2 variants, all IBD patients should receive a third dose, especially if the initial vaccination was performed during immunosuppressive therapy. It should be noted that the doses of immunomodulators commonly prescribed to patients with IBD are lower than those suggested by the JCVI. The specific timing of the third dose should be determined after consideration of the patient’s medical condition and the extent of immunosuppression.
In terms of safety, a recent study on post-vaccination symptoms after the third dose of an mRNA vaccine in patients with IBD (the Coronavirus Risk Associations and Longitudinal Evaluation-IBD study, CORALE-IBD) reported reassuring results. Of the 524 participants, 41% reported post-vaccination symptoms; the frequency and severity were more marked among younger patients. However, these were no worse than after the second dose. Indeed, fewer patients reported symptoms after the third than the second dose [11].
Although data are few, the recommendations for the 2021–2022 influenza vaccination state that such vaccination can accompany COVID-19 vaccination (on the same day). If multiple vaccines are given, the injections should be administered at different sites [9].
SARS-CoV-2-infected pregnant women are at increased risk of intensive care unit admission, a need for mechanical ventilation, and death [12]. Thus, the KDCA recommends vaccination of pregnant women [9]. Although limited IBD-specific data are available, international societies recommend vaccination of pregnant women with and without IBD. Consultation with healthcare providers in terms of vaccination timing and precautions is appropriate.
Clinicians should recommend 3 vaccine doses to IBD patients, especially those on immune-modifying therapies. This recommendation is based on the latest data available at the time of writing (December 18, 2021). As always, the situation may change, and if so, a further update will be prepared.

Funding Source

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

Lee YJ, Park YE, Chang JY, Kim DH, and Myung SJ are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Data Availability Statement

Not applicable.

Author Contribution

Conceptualization: Kim SE, Myung SJ. Data curation: Lee YJ. Supervision: Myung SJ. Visualization: Lee YJ, Kim SE, Park YE, Chang JY, Song HJ, Kim DH, Yang YJ, Kim BC, Lee JG, Yang HC, Myung SJ. Writing - original draft: Lee YJ, Kim SE. Writing - review & editing: Lee YJ, Kim SE, Park YE, Chang JY, Song HJ, Kim DH, Yang YJ, Kim BC, Lee JG, Yang HC. Approval of final manuscript: all authors:

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        Update on SARS-CoV-2 vaccination of patients with inflammatory bowel disease: what clinicians need to know
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