A descriptive study of patients with new onset of inflammatory bowel disease and exacerbations after ChAdOx1-nCoV-19 and inactivated COVID-19 vaccines in a tertiary hospital of North India

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A descriptive study of patients with new onset of inflammatory bowel disease and
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exacerbations after ChAdOx1-nCoV-19 and inactivated COVID-19 vaccines in a tertiary
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hospital of North India
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Upinder Kaur1*, Dondapati Venkata Vamshi Krishna2, Jaideep Reddy2, Noti Taruni Srija
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Reddy2, Amol Dehade3, Sankha Shubhra Chakrabarti4, Dawesh Prakash Yadav5#
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1. MD, Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
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University
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2. MBBS-Intern, Institute of Medical Sciences, Banaras Hindu University
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3. MBBS, Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
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University
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4. MD, Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu
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University
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5. MD, Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu
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University
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# Corresponding Author: Dr. Dawesh Prakash Yadav, Department of Gastroenterology,
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Institute of Medical Sciences, Banaras Hindu University, Phone number: +918130856563
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mail id: devesh.thedoc@gmail.com.
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*Co-corresponding Author: Dr Upinder Kaur, Department of Pharmacology, Institute of
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Medical Sciences, Banaras Hindu University, drupinder.bhu@gmail.com
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Word count: 3530, No. of Tables: 3, Supplementary Table 1
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Running Title: Patterns of inflammatory bowel disease after viral vectored and inactivated
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COVID-19 vaccines.
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Keywords: Adverse events of special interest, COVID-19 vaccines, adenoviral vaccine,
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inflammatory bowel disease, persistent health issues
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Statement and declaration: None
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Conflict of interest: The authors have no relevant financial or non-financial interests to
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disclose.
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Financial support: The authors did not receive support from any organization for the
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submitted work.
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Consent: Written consent was obtained from the participants to participate in the study
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Authorship criteria: All authors meet the ICMJE criteria of authorship.
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Acknowledgements: UK acknowledge the BHU-IoE Scheme for research support
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Ethical approval: The study obtained permission from the Institutional ethics committee
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Data availability statement: The data is largely provided in the Tables. Raw data can be
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shared in accordance with local ethical guidelines and upon reasonable request to the
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Corresponding Authors
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Study highlights:
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What is known:
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• Studies exist on flare of inflammatory bowel disease after m RNA based COVID-19
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vaccines.
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What is new here:
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• We report new onset inflammatory bowel disease and flares after ChAdOx1-nCoV-19
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and inactivated COVID-19 vaccines in terms of time of onset, course of disease,
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changes required in the medications and final outcomes.
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Abstract:
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Background
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Flares of inflammatory bowel disease (IBD) and a few cases of new-onset IBD have been
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reported after mRNA-based COVID-19 vaccines. Reports are scarce with viral vector and
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inactivated COVID-19 vaccines.
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Methods
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Patients diagnosed with ‘flares’ and new-onset IBD after receiving ChAdox1-nCoV-19 and
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inactivated COVID-19 vaccines were recruited from April–July 2022 from the
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Gastroenterology department of a tertiary hospital of North India. Clinical presentation,
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colonoscopy findings, treatment, and outcomes were recorded.
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Results
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A total of 44 patients were identified. 28 patients had flares of IBD at a median interval of 8.1,
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13.2, and 2 weeks since the first, second, and booster doses of COVID-19 vaccines
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respectively. 16 new-onset cases of IBD occurred at a median interval respectively of 4.8, 9,
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and 17.8 weeks after the first, second, and booster doses. The majority of the cases occurred
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after the second dose of ChAdOx1-nCoV-19. With oral amino-salicylic acid (ASA), ASA
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enema, and systemic steroids, improvement was seen in the majority at a median follow-up of
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26-30 weeks. 14 patients had persistent health issues (median follow-up of 73-75 weeks).
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Conclusion
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New-onset IBD and exacerbations can occur after 1-3 months of COVID-19 vaccines.
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Extended surveillance of vaccinated individuals is required to understand the incidence and
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course of late-onset adverse events and molecular studies are warranted to understand their
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immunological basis.
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Keywords: Adenoviral vaccine, adverse events of special interest, BBV152, inflammatory
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bowel disease, persistent health issues
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1. Introduction
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As of 26th February 2024, COVID-19 caused by SARS-CoV-2 has contributed to more than 7
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million deaths worldwide.1 Apart from immediate complications in the form of lung damage
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and pulmonary vascular thrombosis, patients recovering from COVID-19 are at higher risk of
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autoimmune diseases. Increased incidence of rheumatoid arthritis, immune-mediated
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thrombocytopenia, lupus nephritis, and thyroid disturbances has been observed post-COVID-
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19.2 Interestingly, COVID-19 vaccines designed to curb the pandemic have also been
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associated with immune-mediated disturbances such as thrombosis and thrombocytopenia,
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rheumatologic disorders, and thyroid disturbances.3
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Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by
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intestinal manifestations such as abdominal pain, blood in stools, diarrhoea, and extraintestinal
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features such as arthralgia and weight loss. Because many patients of IBD are on
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immunomodulators, concerns were raised regarding the safety and efficacy of COVID-19
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vaccines in this subgroup.4 Concerning safety, few studies predominantly on mRNA-based
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COVID-19 vaccines addressed the incidence of adverse events and disease exacerbation in
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patients of IBD in the early weeks following vaccination.5–8 With respect to new onset, only a
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few isolated cases of IBD have been reported following mRNA-based COVID-19 vaccines.9
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In India, the chimpanzee Adenovirus-based ChAdOx1-nCoV-19 vaccine
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(COVISHIELD/AZD1222) and the inactivated SARS-CoV-2 vaccine (COVAXIN/BBV152)
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were the major COVID-19 vaccines employed during the mass rollout in early 2021. Detailed
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descriptions of new onset IBD and flares of IBD post-use of these vaccines are lacking.
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Particularly scanty is the information on the course of the disease, modifications required in
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the treatment, and long-term outcomes post-vaccination. Through this case series, we describe
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the patterns and outcomes of flares and new onset IBD developing after viral vector and
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inactivated COVID-19 vaccines.
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2. Methodology
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2.1. Study design and setting: This is a descriptive study of a case series of patients
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encountered with flares of IBD or new onset IBD after administration of COVID-19 vaccines,
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who presented to the Gastroenterology outpatient department of the Sir Sunder Lal Hospital
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from April 2022 to July 2022. The Sir Sunderlal Hospital is the teaching hospital of the Institute
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of Medical Sciences, Banaras Hindu University, in the city of Varanasi (Uttar Pradesh state) in
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North India. Patients who were symptomatic at the time of recruitment in the study were
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monitored to record the changes required in medications, disease outcomes, and time of
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recovery. For the patients who were improved at the time of recruitment, such details were
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collected from their past medical records.
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2.2. Study Participants: Participants were individuals with pre-existing diagnosis or
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symptoms of IBD who developed ‘flares’ after COVID-19 vaccination and individuals with
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new-onset IBD who developed symptoms suggestive of IBD after receiving the COVID-19
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vaccines. Patients who refused to provide COVID-19 or vaccination-specific details, who
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developed flares due to poor compliance to therapy, and who did not provide consent to
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participate were excluded.
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2.3. Study parameters: A ‘flare’ was defined as the aggravation of gastrointestinal symptoms
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post-COVID-19 vaccination in patients with a prior diagnosis of IBD whose disease activity
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was previously controlled on or off therapy. New onset IBD was defined as the development
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of symptoms suggestive of IBD post-COVID-19 vaccination with subsequent confirmation by
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colonoscopy and histopathologic examination (HPE) of biopsy specimens. Time of onset,
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pattern of disease, colonoscopy findings, HPE findings, treatment required for management,
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and outcomes were recorded for both ‘flares’ and new onset cases. Any new health issue that
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was persistent for at least a month during the final follow-up was specifically noted and labeled
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as a ‘persistent health issue’.
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2.3. Ethical Issues: Ethical approval was obtained from the Institute Ethics Committee of the
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Institute of Medical Sciences, Banaras Hindu University, and written informed consent was
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taken from all enrolled participants.
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3. Results
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3.1. Flares of IBD post COVID-19 vaccination
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A total of 28 (15 M, 13 F) patients of IBD developed flares after COVID-19 vaccination. Five
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among these had gastrointestinal symptoms suggestive of IBD before receiving the vaccine
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which got aggravated after vaccination and then led to the diagnosis of IBD. Collectively, 21
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of these 28 patients had ulcerative colitis (UC) and 7 patients were of Crohn’s disease (CD)
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(Table 1). The median age of individuals developing flares was 33.5 years. Sixteen of these 28
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patients had no history of a flare in the year preceding vaccination. The majority of cases (n=25)
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occurred after the ChAdOx1-nCoV-19 coronavirus vaccine and were common after the second
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dose of the COVID-19 vaccine (n=18). Five patients had a history of significant adverse events
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(AEs) after vaccination with ChAdOx1-nCoV-19. These AEs included one case each of
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thyrotoxicosis, menstrual abnormality, flare of rheumatoid arthritis, depression/anxiety, and
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pregnancy loss. The time of onset of flares was 8.1 weeks (median), 13.2 weeks (median), and
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2 weeks (mean) after the first dose, second dose, and booster dose of the COVID-19 vaccine
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respectively. Seven patients reported more than one flare till the last follow up and two among
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them had a flare each after a different dose of the inactivated vaccine (COVAXIN). Increased
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stool frequency, blood in stools, and abdominal pain were the three common individual
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manifestations of flares and occurred respectively in 24 (85.7%), 22 (78.6%), and 11 (39.3%)
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patients. Colonoscopy reports were available for nineteen patients and showed the active form
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of the disease in all. Specifically, colonic mucosa showed loss of vascularity, erosions, and
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superficial ulcers in 13 (68.4%), 11 (57.9%), and 11 (57.9%) patients respectively. Therapy
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intensification or the addition of a new drug was required in all patients, except one. Systemic
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steroids (n=14, 50%), amino-salicylic acid (ASA) enema (n=13, 46.4%), and intensification of
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oral ASA (n=13, 46.4%) were the three most common therapeutic modifications. A greater
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percentage (46.4%) of patients required two treatment approach modifications (Table 1). The
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latter commonly included the addition or intensification of oral ASA and the addition of ASA
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enema. The majority of patients (n=10) had been previously controlled on oral ASA and two
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or more treatment approach modifications were needed later in at least eight of them. Seven
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patients were previously controlled off-therapy for a median period of 28 months. Four of these
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were managed post-flare by oral and local ASA, one by the addition of oral ASA, one by the
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addition of oral steroid, and one by the addition of the combination of oral ASA, oral steroid,
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and oral azathioprine. Tofacitinib was needed in one patient and no flare case necessitated
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hospitalization or surgical intervention. Details of previous treatments received by the patients
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(before flares) and the changes required subsequently in the treatment (after flares) are
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mentioned in Supplementary Table S1. The majority of patients (n=25) improved fully with
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therapy intensification after a median follow-up of 30.4 weeks. (Table 1) A total of 10 (35.7%)
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patients complained of persistent health issues during the last follow-up at a median time of
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73.1 weeks since the first dose of the COVID-19 vaccine. Common persistent health issues
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belonged to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class
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of musculoskeletal and connective tissue disorders (such as joint pain) (Table 1).
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3.2. New onset IBD post-COVID-19 vaccination
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A total of 16 new onset cases of IBD (11 UC, and 5 CD) were observed. The median age of
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affected participants was 34 years, and the majority (n=11) were males. (Table 2) ChAdOx1-
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nCoV-19 was involved in 13, followed by BBV152 (n=2) and Sinopharm (n=1). Two patients
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reported significant AEs after ChAdOx1-nCoV-19. These included subclinical hypothyroidism
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in one and severe vomiting and weight loss in another. The majority of new-onset cases (n=11)
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occurred after the second dose of the COVID-19 vaccine. The median time of onset of
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symptoms was 4.8, 9, and 17.8 weeks since the first, second, and booster doses of the COVID-
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19 vaccines respectively. Increased stool frequency, blood in stools, and abdominal pain were
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the common individual symptoms reported by 15 (93.7%), 13 (81.2%), and 12 (75%)
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individuals respectively. Around 69% of patients (n=11) complained of weight loss. All cases
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were diagnosed by colonoscopy and histopathologic examination (HPE) of the colonic biopsy
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specimens. The median (IQR) Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score
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was 4 (3.5-5). Treatment was required in all patients. Oral ASA and systemic steroids were
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required respectively in 14 (87.5%) and 12 (75%) patients. Two and three treatments were
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needed by six patients (37.5%) each. Three patients required hospitalization. Among them one
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required injectable steroids and surgical intervention in the form of enterotomy and ileostomy
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because of extensive intestinal destruction, one required infliximab and the other was
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simultaneously diagnosed with hepatic venous outflow tract obstruction. All except one
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improved fully with treatment after a median follow-up of 25.9 weeks. Two among the sixteen
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cases of new-onset IBD developed a flare before the last follow-up after initial improvement
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and four patients (25%) had persistent health issues at a median follow-up of 75 weeks from
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the first dose. Details of all new onset cases are provided in Table 2 and individual cases are
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described in Table 3.
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4. Discussion
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The present study highlights cases of new-onset IBD and flares of the disease after the receipt
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of viral vector and inactivated coronavirus vaccines in a North Indian population. The majority
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of cases in the present series occurred after the second dose of the COVID-19 vaccine and after
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the ChAdOx1-nCoV-19 vaccine, the major vaccine employed in mass rollout in India. An
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increase in stool frequency, blood in stools, and abdominal pain were the common
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manifestations of flares of IBD as well as new-onset IBD.
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Patients of autoimmune diseases such as IBD were excluded from the pivotal trials of major
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COVID-19 vaccines.10–12 Post-approval, various studies were conducted in patients of IBD
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with the primary objective of the majority being to estimate vaccine effectiveness. Real-world
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studies assessing the exacerbation of IBD activity are predominantly based on mRNA-based
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vaccines. Few among them elaborated on the adverse events following immunization (AEFIs)
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including flares in the initial 2 weeks post-immunization. The rates of flares of IBD in these
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studies have varied from 0.6-18.5%.6,7,13 A rather high rate of IBD flares (44%) was observed
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after 40 days of the second dose of the mRNA-based BNT162b2 vaccine in an Israeli study
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which was presumed to be related to uncontrolled disease activity at baseline.14
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Reports on exacerbations of IBD after viral-vectored and inactivated COVID-19 vaccines are
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scarce. In limited studies such as the PREVENT-COVID, a 0.6% rate of flares (1 out of 161)
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was observed with the rAd26-based Janssen vaccine.5 Rates varying from 5.9-14.9% were
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demonstrated recently with the inactivated vaccines, SinoVac and Sinopharm in China.15,16
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However the information is limited for the details of disease exacerbations, modifications
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required in the treatment, and outcomes of flares.5,6,17 The PREVENT-COVID study of IBD
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patients (n=3316) in the United States had a major representation of mRNA-based COVID-19
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vaccine recipients. The definition of flare considered in that study was the presence of intestinal
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and extraintestinal complaints that worsened within one month of receiving a COVID-19
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vaccine and which required treatment change. Fatigue, extraintestinal symptoms, abdominal
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pain, and increased stool frequency were the symptoms that worsened after COVID-19
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vaccines. Nearly 11-29% of patients complained of these symptoms while only 2.1% could
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meet the definition of a flare. No further details were however provided on the description of
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the flares, modification required in the treatment, and the type of vaccines involved.5 In a
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Japanese study assessing flares of IBD within 30 days of receiving COVID-19 vaccines, flare
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cases were defined based on an increase in partial Mayo score and Harvey-Bradshaw index
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post-COVID-19 vaccination. All nine cases (8 UC, 1 CD) of flares occurred after Pfizer’s
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BNT162b2 vaccine and six among them occurred after the first dose. The majority (88.9%)
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occurred within one week of receiving the vaccine. The median age of affected patients was 62
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years. Three of them required steroid intensification or addition, three needed biological
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therapy, and surgery was needed in one patient of CD. More than half of the cases had
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symptoms lasting for more than 30 days.17 In another survey-based multicentric study in
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European nations, short-term adverse events of COVID-19 vaccination including IBD relapses
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were assessed for mRNA-based COVID-19 vaccines, ChAdOx1-nCoV-19, and other COVID-
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19 vaccines. No definition was provided by the authors for IBD relapse or flares, but 10-12.6%
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of vaccinated individuals complained of abdominal disturbances such as an increase in stool
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frequency and abdominal pain after receiving the vaccines. In the majority of the relapsed
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cases, symptoms resolved spontaneously.6 Aggravation of IBD symptoms has also been
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described after administration of the inactivated COVID-19 vaccine, SinoVac in a survey-
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based study in China.15 Higher rates of IBD exacerbations (14.9%) were reported and common
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symptoms that aggravated were diarrhea, haematochezia, and abdominal pain. Hospitalization
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was also required in a significant proportion (26.7%).15 The study, however, did not define
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flares and neither was the time of assessment of flares or treatment details provided.
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Thus, the limited studies providing evidence on flares of IBD after COVID-19 vaccination
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differ with respect to the definition used for flares, the time of assessment of flares since
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vaccination, the type of COVID-19 vaccines, and the time for recovery. With no known
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biological association between the occurrence of IBD exacerbations and COVID-19
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vaccination, flares have been assessed within 30 days of receiving the vaccine. Details on the
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course of IBD post-ChAdOx1-nCoV-19 and inactivated SARS-CoV-2 vaccines are
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inadequate.
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To address these gaps, one objective of the present case series was to provide descriptive data
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on IBD flares after the viral-vectored ChAdOx1-nCoV-19 vaccine and the inactivated SARS-
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CoV-2 vaccines. The present case series shows flares of IBD occurring after a median time of
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8-13 weeks since the administration of the vaccines. The study was conducted when a major
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proportion of the Indian population had received at least one dose of the COVID-19 vaccine.
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This enabled us to detect the occurrence of late-onset disease exacerbations post-COVID-19
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vaccination in IBD patients. The details of clinical and colonoscopy findings, modifications
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required in IBD medications, and outcomes of disease were procured from the patients lending
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additional strength to the study.
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A greater number of flares were observed in males and patients of UC. In the absence of precise
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estimates of CD, UC is considered the dominant phenotype of IBD in Indian patients.18
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Treatment intensification was required in all except one. Half of the flare cases required
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systemic steroids. A similar percentage needed a dual treatment approach based on the addition
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or intensification of oral ASA and the addition of ASA enema. Overall, all except three cases
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improved fully over 30 weeks.
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Regarding new onset IBD, isolated case reports of UC exist, developing within a week of
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receiving the mRNA-based COVID-19 vaccines, and reports are scanty following receipt of
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other COVID-19 vaccines. 9,19 The second objective of the present study hence was to describe
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the new-onset cases of IBD after administration of the viral vector and inactivated vaccines.
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Among 16 new onset cases of IBD observed in the present study, 11 were of UC and five were
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diagnosed as CD. The male: female ratio was 2.2:1. The exact epidemiological attributes of
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IBD in India are unclear because of underreporting but as per the Global Burden of Disease
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study, the estimates stand close to 162 per million population with a male: female ratio of 1.3-
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1.4:1.20,21 Thus, males might be at higher risk of post-vaccination new onset IBD particularly
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CD as 4 out of 5 new-onset CD cases occurred in males. The majority of new-onset cases
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occurred at a median time lag of 4.8-9 weeks of receiving any dose of a vaccine and were
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managed commonly with oral ASA and systemic steroids. More than 80% of patients required
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two or more treatment approaches comprising oral ASA, ASA enema, and systemic steroids.
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Three cases needed hospitalization and surgical intervention was required in one.
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Notwithstanding the improvement in gastrointestinal symptoms in the majority, 25-36%
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reported new-onset and persistent health issues at 73-75 weeks of follow-up.
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Previously COVID-19 infection has also been associated with a myriad of autoimmune
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disturbances in many database studies.2 Concerning IBD, the evidence is conflicting mainly
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because of the retrospective design of the studies, failure to account for confounders, and the
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negative impact of the pandemic on invasive procedures required for the diagnosis of IBD.22–
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24 However, considering that COVID-19 vaccines are based on the platform of generating
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immunogenicity against the Spike protein of SARS-CoV-2, the occurrence of immune
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conditions post-vaccination is not unanticipated. The post-vaccination era has already
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witnessed a series of adverse events such as myocarditis, atypical thrombosis and
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thrombocytopenia, thyroid disturbances, and rheumatological conditions.3,25
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The onset and exacerbations of IBD are decided by multiple factors. The disease activity is
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governed by crosstalk between immunological, microbial, physiological, and psychological
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factors.26 The mechanism of vaccine-mediated IBD warrants a detailed understanding. The
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adenovirus present in the viral vectored vaccines is sensed by Toll-like receptors (TLRs) such
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as TLR 3, 7, 8, and 9, Nod-like receptors (NLRs), and cyclic GMP/AMP synthase (cGAS)
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dependent pathways. All these pathways enhance the production of interferons via nuclear
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factor κB (NF-κB) signaling. Aberrant sensing of nucleic acids can cause dysregulated
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production of type I interferons, thereby unmasking the autoinflammatory process.27 Cytokines
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such as IL-2, produced in response to adenoviruses or adjuvants also cause activation of
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dormant T cells, thereby producing an inflammatory state.28 SARS-CoV-2 proteins have been
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shown to share significant similarities with various antigens such as mitochondrial protein M2,
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nuclear antigen, thyroid peroxidase, intestinal epithelial cell antigen, histone H1, and tight
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junction proteins such as actin.29,30 Through this mechanism of molecular mimicry, anti-SARS-
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CoV-2 antibodies can produce intestinal inflammation as well as a spectrum of extraintestinal
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manifestations such as rheumatic syndromes and thyroid disturbances. These pathogenetic
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pathways may explain the role of COVID-19 vaccines in IBD and highlight the need for
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mechanistic studies in the future.
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5. Limitations
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The present study is a case series and does not provide conclusive evidence of a causal
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association between COVID-19 vaccines and IBD. Hence whether the observed events were
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caused or precipitated by vaccination or were purely co-incidental is unclear at present. That
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vaccination might have triggered the pathophysiological process to manifest early which was
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otherwise destined to happen over years is another possibility. The time frame of occurrence
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of late-onset immunological events post-COVID-19 vaccination is unknown at present due to
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the scarcity of studies, underreporting, and lack of awareness regarding adverse events of
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special interest. However, a myriad of autoimmune disturbances such as Guillain Barre
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syndrome, myocarditis, vaccine-induced thrombosis, and late-onset thyroid disturbances have
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been witnessed with onset varying from days to 22 weeks since the COVID-19 vaccines.31–33
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The majority of flares and new onset cases of IBD observed by us occurred within 4-13 weeks
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of receiving any dose of a COVID-19 vaccine, a reasonable time frame for any autoimmune
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insult to manifest. Larger, preferably multicentric studies with better inclusion of unvaccinated
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individuals are warranted to understand the incidence and causality of immune-mediated
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disturbances after COVID-19 vaccines. However, with a greater fraction of the population
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vaccinated against COVID-19, selection of unvaccinated groups can be difficult. In such cases,
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case series of atypical adverse events and active monitoring of vaccinated individuals in
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prospective studies are preferred designs to understand the time of occurrence, patterns, and
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course of atypical adverse events. Hence, our study aimed to provide descriptive evidence of
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exacerbations and new-onset cases of IBD after the viral-vectored and inactivated COVID-19
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vaccines for which late-onset immunological disturbances are unstudied. Patients of IBD with
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no history of flares after the COVID-19 vaccine were also not included in the present study
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and hence risk factors among such patients for developing flares after COVID-19 vaccines
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could not be assessed. Though the UCEIS score was arranged in the majority of cases during
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the flare, the definition of flare used was based on subjective reporting of exacerbation of
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gastrointestinal symptoms after vaccination. Incorporation of the Lichtiger score or Mayo’s
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disease activity index can be a better objective measure for assessing the disease activity in
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IBD. In the absence of data on background rates of flares or incidence of IBD in our center, the
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study does not suggest an increased rate of such events. Findings are confined to ChAdOx1-
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nCoV-19 and among inactivated vaccines, to BBV152, which were the major COVID-19
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vaccines distributed in India. The inactivated vaccine, Sinopharm was not distributed in India
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and the one patient with new onset IBD had received the vaccine from China. However, as
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mentioned above, observational studies on flares of IBD after mRNA-based COVID-19
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vaccines are available. Since serological assays for SARS-CoV-2 were not conducted, prior
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asymptomatic or mild COVID-19 could not be excluded. The cases enrolled for the present
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study were selected by convenience sampling and thus there is a chance of underreporting.
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6. Conclusion
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Patients of IBD can have a late exacerbation of the disease after 1-3 months of COVID-19
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vaccines. New onset IBD can occur after 1-3 months of COVID-19 vaccines and males might
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be more predisposed. The majority of cases require the addition or intensification of therapy
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including oral ASA, ASA enema, and systemic steroids, and improve over 6-8 months. Larger
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studies involving unvaccinated individuals are required to understand the link between
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COVID-19 vaccines and autoimmune disturbances. Extended surveillance is warranted for
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COVID-19-vaccinated individuals to comment upon the course of late-onset immunological
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diseases. Molecular mechanisms of vaccine-associated immunological disturbances including
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but not limited to IBD should be explored and patients at risk of post-vaccine autoimmune
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disturbances should be identified.
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Authors’ statements
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Authors’ disclaimers: None
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Authorship criteria: All authors meet the ICMJE criteria of authorship.
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Authors’ contributions:
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UK: Planned and conducted the study, supervised data collection, performed data verification
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and interpretation, conducted review of literature, drafted the manuscript, and approved the
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final draft.
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DVV: Conducted data collection, data verification, data interpretation, data synthesis, and
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approved the final draft.
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JR: Conducted data collection, data verification, contributed to the first draft, and approved the
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final draft
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NTSR: Conducted data collection, data verification, data synthesis, contributed to the first draft,
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conducted review of literature, and approved the final draft.
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AD: Conducted data collection, contributed to data synthesis, first draft, and approved the final
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draft.
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SSC: Conducted review of literature, contributed to data synthesis, final draft, and approved
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the final draft.
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DPY: Contributed to study planning, supervised data collection, involved in patient
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management and maintenance of patients’ registry, and approved the final draft.
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Acknowledgements: UK and SSC acknowledge the BHU-IoE Scheme for research support
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Funding: The authors did not receive any financial support from any organization for the
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submitted work.
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Competing interests: The authors have no relevant financial or non-financial interests to
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disclose.
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Consent: Written consent was obtained from the participants to participate in the study
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Ethical approval: The study obtained permission from the Institutional ethics committee
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Data availability statement: The data is largely provided in the Tables. Raw data can be shared
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in accordance with the local ethical guidelines and upon reasonable request to the
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Corresponding Authors
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