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. 2022 Mar 22;54(6):713–721. doi: 10.1016/j.dld.2022.03.005

Safety of SARS-CoV-2 vaccination in patients with inflammatory bowel disease: A systematic review and meta-analysis

Deepak James a,1, Anuraag Jena a,1, Pardhu Neelam Bharath a, Arup Choudhury a, Anupam K Singh a, Shaji Sebastian b, Vishal Sharma a,⁎
PMCID: PMC8938236  PMID: 35382972

Abstract

Introduction

Risk of adverse effects and flare of inflammatory bowel disease (IBD) are frequently cited reasons for COVID-19 vaccine hesitancy.

Methods

Electronic databases were searched to identify studies reporting the use of COVID-19 vaccine in IBD. We selected studies reporting the incidence of various adverse effects (local or systemic) and flares of IBD after COVID-19 vaccination. The pooled incidence rates for various adverse effects, stratified for the dose and the type of vaccine (adenoviral or mRNA) were estimated.

Results

Nine studies (16 vaccination cohorts) were included. The pooled incidence rate of overall adverse events was 0.55 (95%CI, 0.45–0.64, I2= 95%). The pooled incidence rate of local adverse events was 0.64 (0.47–0.78, I2= 100%). The pooled incidence rates of fatigue, headache, myalgia, fever and chills were 0.30 (0.21–0.40, I2= 99%), 0.23 (0.17–0.30, I2= 99%), 0.18 (0.13–0.24, I2= 99%), 0.10 (0.06–0.17, I2= 98%) and 0.15 (0.06–0.3, I2= 86%), respectively. The pooled incidence rates of severe adverse events, adverse events requiring hospitalization and flares of IBD following COVID-19 vaccination were 0.02 (0.00–0.12, I2= 97%), 0.00 (0.00–0.01, I2= 27%) and 0.01 (0.01–0.03, I2= 45%), respectively.

Conclusion

COVID-19 vaccination in patients with IBD appears to be safe with only mild adverse events. Flares of IBD and severe adverse events requiring hospitalization were infrequent.

Keywords: Crohn's disease, SARS-CoV-2, Side-effect, Ulcerative colitis

1. Introduction

COVID-19 vaccination is recommended as an important strategy to control the pandemic. Various society guidelines recommend a full course of COVID-19 vaccination along with a booster dose [1], [2], [3], [4]. The management of patients with IBD has been a challenge amidst the COVID-19 pandemic [1]. Regardless of biological therapies or immunomodulators use, the non-live vaccines are generally considered safe in patients with IBD. The trials of the vaccines which led to the emergency approval had excluded patients of both ulcerative colitis (UC) and Crohn's disease (CD). The response to vaccination in patients with IBD on various immune modifying drugs, was variable [5,6]. The concerns regarding adverse events of COVID-19 vaccination increased after reports of thrombotic events following vaccination. The FDA had to issue a statement suggesting that the benefits outweigh the risks. The adverse events following vaccination are an important concern among the patients with IBD [7,8]. The concerns include possible adverse events, flaring of the underlying IBD and decreased responsiveness to vaccines. The concern for adverse events has been a major reason for vaccine hesitancy among patients with IBD [7,8].

Despite encouraging data on vaccine efficacy in IBD, there is limited information on adverse effects of various COVID-19 vaccines. We performed a systematic review and single-arm meta-analysis on the various adverse events following COVID-19 vaccination in patients with IBD in order to inform the clinicians and patients regarding the (lack of) risks) of COVID vaccination.

2. Methods

This meta-analysis was conducted in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group recommendations and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance [9,10].

2.1. Database search

A literature search was done in electronic databases using PubMed and Embase (recent till 17 December, 2021) using the keywords inflammatory bowel disease, ulcerative colitis, Crohn's disease combined using the operator ‘AND’ COVID-19, SARS-COV-2 AND Vaccine or Vaccination or Immunization. The detailed strategy is described in Supplementary Table 1. The bibliographies of eligible studies were also searched for additional papers. Preprint servers medRxiv and bioRxiv were also searched for any additional papers. The eligible titles were combined and the duplicates were removed. The titles and abstracts were then reviewed by two reviewers (DJ and PB). After screening of titles and abstracts, full text screening was done (DJ, AJ, AC). Any differences were resolved after discussion with a third reviewer (VS).

2.2. Inclusion and exclusion criteria

We included all relevant articles (uncontrolled, single-arm prospective / retrospective studies including abstracts) pertaining to adverse events of COVID-19 vaccines or the language of publication, in the systematic review. We included studies reporting at least one of following outcomes in IBD-

  • 1.

    Adverse events or side effects following COVID-19 vaccination.

  • 2.

    Flare of underlying disease following COVID-19 vaccination.

We excluded case reports, case series (< 10 cases), surveys, reviews, guidelines, editorials and studies which did not report relevant data about adverse events after vaccination. Studies which reported seroconversion rates after COVID vaccination were included in full text screening to look for any additional information regarding adverse events.

2.3. Data extraction

The data was extracted from the appropriate studies by two reviewers (DJ and PB) and any disagreement was resolved by discussion with the third reviewer (VS). The data was extracted irrespective of the type (mRNA or Adenoviral) or dose of vaccine. We extracted data regarding the details of the publication (name of author and location), underlying population (ulcerative colitis or Crohn's disease), underling disease activity, characteristics of patients (age, gender, concomitant drugs), type of vaccine (mRNA or AAV), number of doses (first or second dose) and details of adverse events.

2.4. Outcomes

We performed a single-arm meta-analysis (pooled data analysis) in absence of control arms. The pooled incidence rates of adverse events after COVID-19 vaccine were calculated. We calculated the pooled incidence rates of both the local and systemic adverse events following vaccination. The definitions of local or systemic adverse event were used as defined in individual studies. We also calculated the pooled rates of flare of underlying disease activity in IBD, severe adverse events and adverse events requiring hospitalization after COVID vaccination. The analysis was performed separately for single and double dose vaccine regimens.

2.5. Data analysis

The analysis was conducted using the R statistical software, version 4.0.1. In addition to it, meta and metafor packages for R were also used [11,12]. The pooled rates of each adverse event was calculated using the random effects model with inverse variance approach. The random effects model was chosen because of the underlying heterogeneity in the studies, included population, vaccines and doses, and the reported outcomes. Subgroup analysis was conducted for calculating the pooled adverse events rate depending on the type and dose of vaccine. The heterogeneity was determined by I2 and P value of heterogeneity. A standard continuity correction of 0.5 was applied when the number of events was zero.

2.5.1. Methodological quality and risk of bias assessment

Two of the investigators (DJ and AJ) independently assessed the methodological quality and risk of bias of studies using the Newcastle Ottawa Scale (NOS) for cohort studies [13]. Any discordance in risk of bias, was settled with mutual agreement with a third reviewer (VS). The included studies were rated as having good/ fair or poor quality as per the scale provided along with the NOS table (Supplementary Table 3).

3. Results

The search yielded 429 citations. ( Fig. 1 , PRISMA flow chart) Of the total of 429 studies, there were 95 duplicates. We excluded 302 citations after abstract screening. We obtained 3 further studies after manual searching of the references of included studies. After full text screening of 35 articles, we excluded 26 studies not fulfilling inclusion criteria. Eventually, 9 studies (8 full texts and one abstract) with 16 cohorts were included in the final analysis. The details of the included studies are illustrated in Table 1 [14], [15], [16], [17], [18], [19], [20], [21], [22]. The details of the excluded studies with the reason for exclusion is shown in Supplementary Table 2 [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48].

Fig. 1.

Fig 1

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PRISMA flow chart depicting the study screening and selection of the systematic review.

Table 1.

The included studies with details regarding the included population and vaccination.

Authors Country Type of study Vaccine type, Vaccination status (Complete/ Incomplete/ Mixed)
 Number of patients
 Dose breakup
 Adverse events
 Follow up duration
mRNA mRNA type AAV AAV type Total Mean Age (SD) (years) Female CD UC Disease activity Drugs D1 D2 Total Local Systemic Miscellaneous
Dailey et al. [14] USA Prospective longitudinal cohort study 28
Mixed		 21 - Pfizer-BioNTech
7 - Moderna
 5
Complete		 Johnson & Johnson 5 33 NA NA NA NA Not mentioned NA 33 28 NA NA NA NA 2 weeks to 6 months
Botwin et al. [15] USA Prospective longitudinal study 246
Mixed		 141- Pfizer- BioNTech, 105 - Moderna
 0 0 246 47.4 (15.5) 139 165 81 Not mentioned Oral/ rectal Sulfasalazine/ mesalamine, Budesonide, Oral/ parenteral steroids, 6MP/ Azathioprine, Methotrexate, Anti TNF, Anti integrin, IL12/23 inhibitor, JAK inhibitor 246 NA 96 93 NA NA At least 7 days
Wong et al. [16] USA Longitudinal nested case-control study 48
Mixed		 23 – Pfizer-BioNTech, 25 -NIH-Moderna 0 0 48 49.1 (20.2) 25 23 25 Not mentioned Infliximab, Adalimumab, Vedolizumab,
Ustekinumab,
Tofacitinib, Oral steroids, Immunomodulator, Mesalamine,
No medications		 48 26 29 19 NA NA 85 days
Edelman-Klapper et al. [17] Israel Multicenter prospective observational study 185
Mixed		 Pfizer-BioNTech 0 0 185 38.1(14.3) 73 122 53 120 – remission
65 - active disease
 Infliximab,
Adalimumab, Vedolizumab, Ustekinumab, 5-ASA, Steroids, Immunomodulators, JAK inhibitor		 185 185 Expressed dose-wise 30 days median
Garrido et al. [18] Portugal Single center longitudinal cohort study 190
Mixed		 141 - Pfizer-BioNTech,
49 - Moderna		 49
Mixed		 34 - Johnson & Johnson, 15 - AstraZeneca 239 NA NA NA NA Not mentioned Anti TNF, Ustekinumab, Vedolizumab 239 173 Expressed dose-wise NA
Cannatelli et al. [19] Italy Prospective study 470
Mixed		 320 - Pfizer-BioNTech,
150 - Moderna		 18
Mixed		 AstraZeneca 488
 55.3 (14.4) 270 233 246 397 – remission,
91 – active disease		 No treatment, Mesalamine, Corticosteroids, Azathioprine, Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab, Tofacitinib 488 433 228 Expressed dose-wise NA
Weaver et al. [10] USA Prospective observational cohort study 3155
Mixed		 1908 - Pfizer-BioNTech,
1247 - Moderna		 161
Complete		 Johnson & Johnson 3316
 43.7 (15.1) 2378 1811 NA 1077 – remission
2239 – active disease		 Oral/parenteral steroids, Oral budesonide, Oral mesalamine, Sulfasalazine, Thiopurine, Methotrexate, Infliximab, Adalimumab, Certolizumab, Golimumab, Vedolizumab, Ustekinumab, Tofacitinib, Cyclosporine, Tacrolimus 3316 3080 Expressed dose-wise Up to 7 days
Mujukian et al. [21] USA longitudinal case control study 1391
Mixed		 828 - Pfizer-BioNTech,
563 - Moderna		 0 0 1391 NA 873 904 487 Not mentioned NA 1391 1271 Expressed dose-wise On Day 7
Classen et al. [22] Germany Retrospective observational Heterogeneous data 72 48.4 (15.2) 38 40 32 Not mentioned,
One case was in flare		 Steroids, Mesalazine, Azathioprine, Methothrexate, Calcineurin inhibitor, Anti
TNF, Anti integrin, JAK inhibitors, Ustekinumab		 NA NA Expressed dose-wise NA
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3.1. Total adverse events in patients with IBD following vaccination

There were 6 studies (9 cohorts, 3930 patients) reporting adverse events following COVID-19 vaccination in patients with IBD. The pooled incidence rate of adverse events in IBD patients following COVID-19 vaccination was 0.55 (95%CI, 0.45–0.64, I2 = 95%) ( Fig. 2 ). There were 3 studies (4 cohorts, 2944 patients) reporting adverse events following m-RNA based COVID-19 vaccination in patients with IBD. The pooled incidence rate of adverse events in IBD patients following only m-RNA based COVID-19 vaccination was 0.52 (95%CI, 0.33–0.71, I2 = 95%) ( Fig. 2 ). There were 4 studies of 1948 patients and 4 studies of 1946 patients reporting adverse events following single and double dose vaccination, respectively. The pooled incidence rate of adverse events in IBD patients following single dose COVID-19 vaccination was 0.47 (95%CI, 0.36–0.58, I2 = 93%) ( Fig. 3 ). The pooled incidence rate of adverse events in IBD patients following double dose COVID-19 vaccination was 0.57 (95%CI, 0.45–0.69, I2 = 89%) ( Fig. 3).

Fig. 2.

Fig 2

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Adverse events following COVID-19 vaccination in patients with IBD subtyped for type of vaccine.

Fig. 3.

Fig 3

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Adverse events following COVID-19 vaccination in patients with IBD subtyped for dose of vaccine.

3.2. Local adverse events following vaccination in patients of IBD

There were 5 studies (8 cohorts, 9710 patients) reporting local injection site adverse events following COVID-19 vaccination. The pooled incidence rate of local adverse events in IBD patients following COVID-19 vaccination was 0.64 (95%CI, 0.47–0.78, I2 = 100%) ( Fig. 4 ). The pooled incidence rate of local adverse events following mRNA based COVID-19 vaccination was 0.53 (95%CI, 0.40–0.66, I2 = 97%) ( Fig. 4). The pooled incidence rate of local adverse events following a single dose COVID-19 vaccination was 0.60 (95%CI, 0.32–0.83, I2 = 100%) (Supplementary Fig. 1). The pooled incidence rate of local adverse events following a double dose of COVID-19 vaccination was 0.71 (95%CI, 0.47–0.87, I2 = 100%) (Supplementary Fig. 1). The pooled incidence rate of soreness of the arm was 0.52 (95%CI, 0.43–0.60, I2 = 98%) (Supplementary Fig. 2). Supplementary Table 4 provides definitions for local and systemic adverse events as used in individual studies.

Fig. 4.

Fig 4

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Local adverse events following COVID-19 vaccination in patients with IBD subtyped for type of vaccine.

3.3. Systemic adverse events following vaccination in patients of IBD

The pooled incidence rate of fever and chills following COVID-19 vaccination in patients of IBD was 0.10 (95%CI, 0.06–0.17, I2 = 98%) and 0.15 (95%CI, 0.06–0.3, I2 = 86%), respectively (Supplementary Figs. 3 and 4). The pooled incidence rate of fatigue and myalgia following COVID-19 vaccination in patients of IBD was 0.30 (95%CI, 0.21–0.40, I2 = 99%) and 0.18 (95%CI, 0.13–0.24, I2 = 99%), respectively (Supplementary Figs. 5 and 6). The pooled incidence rate of headache following COVID-19 vaccination in patients of IBD was 0.23 (95%CI, 0.17–0.30, I2 = 99%) (Supplementary Fig. 7) while for joint pain it was 0.10 (95%CI, 0.06–0.17, I2 = 98%) (Supplementary Fig. 8). The pooled incidence rate of skin rash following COVID-19 vaccination in patients of IBD was 0.01 (95%CI, 0.01–0.01, I2=29%) (Supplementary Fig. 9). The pooled incidence rate of gastrointestinal adverse events following vaccination in patients with IBD was 0.08 (95%CI, 0.05–0.12, I2 = 97%) (Supplementary Fig. 10).

3.4. Severe adverse events following vaccination in patients of IBD

Of the 6 studies (7590 total events) the pooled rates of severe adverse events were 0.02 (95%CI, 0.00–0.12, I2 = 97%) (Fig. 5 , Top Panel). There were 5 studies (7 cohorts, 7578 patients) reporting adverse events requiring hospitalization in IBD following COVID-19 vaccination. The pooled incidence rate of adverse events requiring hospitalization following COVID-19 vaccination was 0.00 (95%CI, 0.00–0.01, I2 = 27%) ( Fig. 5 - Middle panel).

Fig. 5.

Fig 5

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Top panel: severe Adverse events following COVID-19 vaccination in patients with IBD; Middle Panel: adverse events requiring hospitalization following COVID-19 vaccination in patients with IBD; bottom panel: adverse events causing flare of disease in IBD following COVID-19 vaccination.

3.5. IBD flare following vaccination

There were 4 studies (6 cohorts, 4537 patients) reporting flare of disease in IBD following COVID-19 vaccination. The pooled incidence rate of flare of disease following COVID-19 vaccination was 0.01 (95%CI, 0.01–0.03, I2 = 45%) ( Fig. 5 - bottom panel).

3.6. Risk of bias analysis

The quality analysis of the included studies was done using Newcastle-Ottawa Quality Assessment Form for Cohort Studies. The results of the assessment are shown in Supplementary Table 3 [14], [15], [16], [17], [18], [19], [20], [21], [22]. Of the included studies, two studies were of good quality, three studies were of fair quality and four studies were of poor quality.

4. Discussion

SARS-CoV2 virus, being a mutating virus with emerging variants of concern, vaccination remains the core strategy for control of the pandemic [49]. In the real-world analysis of patients of IBD, adverse events following COVID-19 vaccination were seen in nearly half of the entire cohort irrespective of the dose of vaccine. However, most of these were local adverse events, the majority being injection site related. Systemic adverse events following vaccination were rare with the majority not requiring hospitalization. Fatigue, headache, myalgia, fever and chills were the most common systemic adverse events following COVID-19 vaccination. The findings suggest that COVID-19 vaccination is safe for patients with IBD.

Fear of adverse events especially flare of disease activity in IBD remains a major concern in patients with IBD [7,8,50]. This is one of the important causes of vaccine hesitancy in patients with IBD. A survey in Italy revealed fear of negative impact on the course of IBD was seen in 52% of respondents [51]. To address this, we found gastrointestinal related adverse effects were also low in incidence and a flare of underlying disease activity in IBD following vaccination was seen in extremely small numbers. The data reaffirms the fact that vaccination has minimal impact on the course of disease in IBD.

The risk of adverse events in a survey in China was seen at 88% and was one of the major reasons behind the lack of intention to take vaccines [52]. Other causes include concern that vaccines are being made quickly. The findings of our meta-analysis show a majority of adverse events were limited to injection site side effects. Systemic adverse events were reported only in a small subset. Adverse events of importance like immune mediated thrombocytopenia, Guillain-Barré syndrome, transverse myelitis, stroke, deep vein thrombosis, myocarditis and myocardial infarction were reported in a study and was seen in a minority (2.03%) of patients of IBD [31]. There is a need for close monitoring and reporting of these severe adverse events in patients of IBD.

There were similar adverse events after the first or second dose of COVID-19 vaccine in patients with IBD. The pooled incidence rates were similar between the first and second dose of COVID-19 vaccine. There was only one study reporting about adverse events after the third dose and showed adverse events in 41% of the patients [36]. They found that the adverse events were similar to that of the second dose while post vaccination symptoms were lower than that of the second dose. Data from vaccination in general population suggest that of a cohort with 655 590 doses (mRNA and AAV), systemic side-effects occurred in 13•5% and 33.7% after first dose of mRNA and AAV vaccine, respectively and 22•0% after second dose of mRNA vaccine. Local side-effects were reported 71.9% and 58.7% after first dose of mRNA and AAV vaccine, respectively and 68•5% after the second dose of mRNA vaccine [53]. The local adverse events are comparable to our analysis in IBD patients. We do not have estimates for systemic adverse events overall for IBD patients.

There are some limitations of the study. There is no control arm in most studies. We could not address the impact of age, comorbidities and drugs on the incidence of adverse events by a meta-regression largely due to small number of studies (< 10). There were only two studies reporting AAV related adverse events. Lastly, the included studies were not homogeneous with some studies reporting mixed vaccine schedules. The assessment for publication bias could not be done using the relevant statistical tests due to small number of studies. Also, there could be an overlap in certain definition e.g. gastrointestinal symptoms and flare of IBD. We have used the definitions exactly as provided in individual studies (Supplementary Table 4); it clearly shows that some studies consider flares as a component of gastrointestinal symptoms while others considered these as separate entities. Further although we have done subgroup analysis of adverse events after one or two dose, this is not the same as incomplete or complete vaccination. Certain vaccines like Janssen may have a single dose only in the complete schedule.

To conclude, the meta-analysis confirms that COVID-19 vaccine is safe in patients with IBD and not associated with flares of disease. This study should reduce the vaccine hesitancy among the patients with IBD and the clinicians should affirm that benefits outweigh the risks. Future studies should look into adverse events of each vaccine type and critically look into mechanisms of severe adverse events following vaccination. Post marketing surveillance of vaccine related adverse events especially of patients of pediatric population, elderly and with comorbidities are needed.

Conflict of interest

None declared.

Funding

None.

Footnotes

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.dld.2022.03.005.

Appendix. Supplementary materials

mmc1.docx (1.2MB, docx)

References

  • 1.Singh A.K., Jena A., Kumar M.P., Sharma V., Sebastian S. Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: a systematic review and meta-analysis. United Eur Gastroenterol J. 2021;9(2):159–176. doi: 10.1177/2050640620972602. MarEpub 2021 Mar 23. PMID: 33210980; PMCID: PMC8250629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Siegel C.A., Melmed G.Y., McGovern D.P., Rai V., Krammer F., Rubin D.T., Abreu M.T., Dubinsky M.C., International Organization for the Study of Inflammatory Bowel Disease (IOIBD); International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting. Gut. 2021;70(4):635–640. doi: 10.1136/gutjnl-2020-324000. AprEpub 2021 Jan 20. PMID: 33472895; PMCID: PMC7818789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Alexander J.L., Moran G.W., Gaya D.R., Raine T., Hart A., Kennedy N.A., Lindsay J.O., MacDonald J., Segal J.P., Sebastian S., Selinger C.P., Parkes M., Smith P.J., Dhar A., Subramanian S., Arasaradnam R., Lamb C.A., Ahmad T., Lees C.W., Dobson L., Wakeman R., Iqbal T.H., Arnott I., Powell N., Inflammatory Bowel Disease section of the British Society of Gastroenterology and the the Inflammatory Bowel Disease Clinical Research Group SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British society of gastroenterology inflammatory bowel disease section and IBD clinical research group position statement. Lancet Gastroenterol Hepatol. 2021;6(3):218–224. doi: 10.1016/S2468-1253(21)00024-8. MarEpub 2021 Jan 26. PMID: 33508241; PMCID: PMC7834976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Alexander J.L., Selinger C.P., Powell N., British Society of Gastroenterology Inflammatory Bowel Disease section and the Inflammatory Bowel Disease Clinical Research Group Third doses of SARS-CoV-2 vaccines in immunosuppressed patients with inflammatory bowel disease. Lancet Gastroenterol Hepatol. 2021;6(12):987–988. doi: 10.1016/S2468-1253(21)00374-5. DecEpub 2021 Oct 13. PMID: 34653395; PMCID: PMC8511687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Sakuraba A., Luna A., Micic D. Serologic response to coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated inflammatory diseases: a systematic review and meta-analysis. Gastroenterology. 2022;162(1):88–108. doi: 10.1053/j.gastro.2021.09.055. Jane9Epub 2021 Sep 29. PMID: 34599933; PMCID: PMC8479970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Jena A., Mishra S., Deepak P., Kumar-M P., Sharma A., Patel Y.I., Kennedy N.A., Kim A.H.J., Sharma V., Sebastian S. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: systematic review and meta-analysis. Autoimmun Rev. 2021;21(1) doi: 10.1016/j.autrev.2021.102927. Aug 30Epub ahead of print. PMID: 34474172; PMCID: PMC8404391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Dalal R.S., McClure E., Marcus J., Winter R.W., Hamilton M.J., Allegretti J.R. COVID-19 vaccination intent and perceptions among patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2021;19(8):1730–1732. doi: 10.1016/j.cgh.2021.02.004. Auge2Epub 2021 Feb 4. PMID: 33549869; PMCID: PMC7859624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Wu X., Lin J., Buch H., Ding Q., Zhang F., Cui B., Ji G. The COVID-19 vaccination hesitancy among the people with inflammatory bowel disease in China: a questionnaire study. Front Public Health. 2021;9 doi: 10.3389/fpubh.2021.731578. Oct 11PMID: 34708016; PMCID: PMC8542757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Stroup D.F., Berlin J.A., Morton S.C., Olkin I., Williamson G.D., Rennie D., Moher D., Becker B.J., Sipe T.A., Thacker S.B. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–2012. doi: 10.1001/jama.283.15.2008. Apr 19PMID: 10789670. [DOI] [PubMed] [Google Scholar]
  • 10.Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., Chou R., Glanville J., Grimshaw J.M., Hróbjartsson A., Lalu M.M., Li T., Loder E.W., Mayo-Wilson E., McDonald S., McGuinness L.A., Stewart L.A., Thomas J., Tricco A.C., Welch V.A., Whiting P., Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. Mar 29PMID: 33782057; PMCID: PMC8005924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Balduzzi S., Rücker G., Schwarzer G. How to perform a meta-analysis with {R}: a practical tutorial. Evid Based Ment Health. 2019;22:153–160. doi: 10.1136/ebmental-2019-300117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48. doi: 10.18637/jss.v036.i03. [DOI] [Google Scholar]
  • 13.Wells G., Shea B., O'Connell D., Peterson J., Welch V., Losos M., Tugwell P.: The newcastle-ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2013, http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
  • 14.Dailey J., Kozhaya L., Dogan M., et al. Antibody responses to SARS-CoV-2 after infection or vaccination in children and young adults with inflammatory bowel disease. Inflamm Bowel Dis. 2021:izab207. doi: 10.1093/ibd/izab207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Botwin G.J., Li D., Figueiredo J., et al. Adverse events after SARS-CoV-2 mRNA vaccination among patients with inflammatory bowel disease. Am J Gastroenterol. 2021;116(8):1746–1751. doi: 10.14309/ajg.0000000000001342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Wong S.Y., Dixon R., Martinez Pazos V., et al. Serologic response to messenger RNA coronavirus disease 2019 vaccines in inflammatory bowel disease patients receiving biologic therapies. Gastroenterology. 2021;161(2):715–718. doi: 10.1053/j.gastro.2021.04.025. e4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Edelman-Klapper H., Zittan E., Bar-Gil Shitrit A., et al. Lower serologic response to COVID-19 mRNA Vaccine in patients with inflammatory bowel diseases treated with anti-TNFα. Gastroenterology. 2022;162(2):454–467. doi: 10.1053/j.gastro.2021.10.029. S0016-5085(21)03701-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Garrido I., Lopes S., Macedo G. "Safety of COVID-19 vaccination in inflammatory bowel disease patients on biologic therapy". J Crohns Colitis. 2021:jjab189. doi: 10.1093/ecco-jcc/jjab189. [published online ahead of print, 2021 Oct 30] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Cannatelli R., Ferretti F., Carmagnola S., et al. Risk of adverse events and reported clinical relapse after COVID-19 vaccination in patients with IBD. Gut. 2021 doi: 10.1136/gutjnl-2021-326237. [published online ahead of print, 2021 Nov 24] gutjnl-2021-326237. [DOI] [PubMed] [Google Scholar]
  • 20.Weaver K.N., Zhang X., Dai X., et al. Impact of SARS-CoV-2 vaccination on inflammatory bowel disease activity and development of vaccine-related adverse events: results from PREVENT-COVID. Inflamm Bowel Dis. 2021:izab302. doi: 10.1093/ibd/izab302. [published online ahead of print, 2021 Dec 6] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Mujukian A., Botwin G., Kumar R., et al. S950-Symptomology following SARS-CoV-2 mRNA vaccination among patients with inflammatory bowel disease relative to healthcare workers. Am J Gastroenterol. 2021;116:S453–S455. October. [Google Scholar]
  • 22.Classen J.M., Muzalyova A., Nagl S., et al. Antibody response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease - results of a single-center cohort study in a tertiary hospital in Germany. Digit Distrib. 2021 doi: 10.1159/000521343. [published online ahead of print, 2021 Dec 10] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Abdullah L., Awada B., Kurban M., Abbas O. Comment on ‘Vitiligo in a COVID-19-vaccinated patient with ulcerative colitis: coincidence?’: type I interferons as possible link between COVID-19 vaccine and vitiligo. Clin Exp Dermatol. 2021;47(2):436–437. doi: 10.1111/ced.14932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Alexander J.L., Kennedy N.A., Lees C.W., Ahmad T., Powell N. SARS-CoV-2 vaccination for patients with inflammatory bowel disease – authors' reply. Lancet Gastroenterol Hepatol. 2021;6(7):523–524. doi: 10.1016/S2468-1253(21)00194-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Cerna K., Duricova D., Lukas M., Machkova N., Hruba V., Mitrova K., et al. Anti-SARS-CoV-2 vaccination and antibody response in patients with inflammatory bowel disease on immune-modifying therapy: prospective single-tertiary study. Inflamm Bowel Dis. 2021 doi: 10.1093/ibd/izab301. [DOI] [PubMed] [Google Scholar]
  • 26.D'Amico F., Rabaud C., Peyrin-Biroulet L., Danese S. SARS-CoV-2 vaccination in IBD: more pros than cons. Nat Rev Gastroenterol Hepatol. 2021;18(4):211–213. doi: 10.1038/s41575-021-00420-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Doherty J., Fennessy S., Stack R., Om N., Cullen G., Ryan E.J., et al. Review article: vaccination for patients with inflammatory bowel disease during the COVID-19 pandemic. Aliment Pharmacol Ther. 2021;54(9):1110–1123. doi: 10.1111/apt.16590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Fagni F., Simon D., Tascilar K., Schoenau V., Sticherling M., Neurath M.F., et al. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021;3(10):e724–ee36. doi: 10.1016/S2665-9913(21)00247-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Festa S., Aratari A., De Biasio F., Fascì-Spurio F., Papi C. Screening for active COVID-19 infection prior to biologic therapy in IBD patients: let's not increase our uncertainty without reducing our concerns. Dig Liver Dis. 2020;52(11):1246–1247. doi: 10.1016/j.dld.2020.05.037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Garrido H.M.G., Grobusch M.P., D'Haens G., Goorhuis A. SARS-CoV-2 vaccination for patients with inflammatory bowel disease. Lancet Gastroenterol Hepatol. 2021;6(7):523. doi: 10.1016/S2468-1253(21)00148-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Hadi Y.B., Thakkar S., Shah-Khan S.M., Hutson W., Sarwari A., Singh S. COVID-19 vaccination is safe and effective in patients with inflammatory bowel disease: analysis of a large multi-institutional research network in the United States. Gastroenterology. 2021;161(4):1336–1339. doi: 10.1053/j.gastro.2021.06.014. e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Kothadia S., Ward C., Akerman P. New diagnosis of severe ulcerative colitis immediately following mRNA-1273 SARS-CoV2 vaccination. Am J Gastroenterol. 2021;116:S1027. [Google Scholar]
  • 33.Kumar R., Botwin G.J., Horizon A., Appel K.L., Mujukian A., Boland B., et al. Gastrointestinal symptoms in patients with inflammatory bowel disease after SARS-CoV-2 mRNA vaccination. Am J Gastroenterol. 2021;116:S427–S4S8. [Google Scholar]
  • 34.Latypov L., Khan A., Manohar H., Bhagat U. Acute exacerbation of Crohn's disease after COVID-19 Pfizer vaccine. Am J Gastroenterol. 2021;116:S1025. [Google Scholar]
  • 35.Levine I., Swaminath A., Roitman I., Sultan K. COVID-19 vaccination and inflammatory bowel disease: desired antibody responses, future directions, and a note of caution. Gastroenterology. 2022;162(1):349–350. doi: 10.1053/j.gastro.2021.05.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Li D, Debbas P, Cheng S, Braun J, McGovern DPB, Melmed GY. Post-Vaccination Symptoms after A Third Dose of mRNA SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease. medRxiv [Preprint]. 2021 Dec 7:2021.12.05.21266089. doi: 10.1101/2021.12.05.21266089. PMID: 34909797; PMCID: PMC8669864. [DOI]
  • 37.Melmed G.Y., Rubin D.T., McGovern D.P.B. Winter is coming! Clinical, immunologic, and practical considerations for vaccinating patients with inflammatory bowel disease during the coronavirus disease-2019 pandemic. Gastroenterology. 2021;160(3):639–644. doi: 10.1053/j.gastro.2020.10.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Murthy S.K., Kuenzig M.E., Windsor J.W., Ghia J.E., Griffiths A.M., Panaccione R., et al. Crohn's and colitis Canada's 2021 impact of COVID-19 and inflammatory bowel disease in Canada: COVID-19 vaccines-biology, current evidence and recommendations. J Can Assoc Gastroenterol. 2021;4:S54–S60. doi: 10.1093/jcag/gwab033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Prentice R.E., Rentsch C., Al-Ani A.H., Zhang E., Johnson D., Halliday J., et al. SARS-CoV-2 vaccination in patients with inflammatory bowel disease. GastroHep. 2021;3(4):212–228. doi: 10.1002/ygh2.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Sangha M., Roitman I., Sultan K., Swaminath A. SARS-CoV-2 immunization in patients with inflammatory bowel disease may result in disease flares. Am J Gastroenterol. 2021;116(12):2480–2481. doi: 10.14309/ajg.0000000000001416. [DOI] [PubMed] [Google Scholar]
  • 41.Shah S.R.A., Dolkar S., Mathew J., Vishnu P. COVID-19 vaccination associated severe immune thrombocytopenia. Exp Hematol Oncol. 2021;10(1):42. doi: 10.1186/s40164-021-00235-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Siegel C.A., Melmed G.Y., McGovern D.P.B., Rai V., Krammer F., Rubin D.T., et al. SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting. Gut. 2021;70(4):635–640. doi: 10.1136/gutjnl-2020-324000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Spencer E.A., Klang E., Dolinger M., Pittman N., Dubinsky M.C. Seroconversion following SARS-CoV-2 infection or vaccination in pediatric IBD patients. Inflamm Bowel Dis. 2021;27(11):1862–1864. doi: 10.1093/ibd/izab194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Spiera E., Agrawal M., Ungaro R. COVID-19 mRNA vaccine short-term safety in patients with inflammatory bowel disease. Gastroenterology. 2022;162(3):987–988. doi: 10.1053/j.gastro.2021.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Squire J.D., Gonzalez-Estrada A., Caldera F., Farraye F.A. COVID-19 vaccination in patients with inflammatory bowel disease and history of reaction to injectable therapies. Inflamm Bowel Dis. 2021;27(8):1358–1360. doi: 10.1093/ibd/izab094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Tepasse P.R., Vollenberg R., Nowacki T.M. Vaccination against SARS-CoV-2 in patients with inflammatory bowel diseases: where do we stand? Life. 2021;11(11) doi: 10.3390/life11111220. (Basel) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Tse F., Moayyedi P., Waschke K.A., MacMillan M., Forbes N., Carroll M.W., et al. COVID-19 vaccination in patients with inflammatory bowel disease: communiqué from the canadian association of gastroenterology. J Can Assoc Gastroenterol. 2021;4(1):49. doi: 10.1093/jcag/gwaa046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Veereman G., Bronsky J. Severe acute respiratory syndrome coronavirus 2 vaccination for paediatric patients with inflammatory bowel diseases. J Pediatr Gastroenterol Nutr. 2021;73(4):433–436. doi: 10.1097/MPG.0000000000003260. [DOI] [PubMed] [Google Scholar]
  • 49.Wellens J., Colombel J.F., Satsangi J.J., Wong S.Y. SARS-CoV-2 vaccination in IBD: past lessons, current evidence, and future challenges. J Crohns Colitis. 2021;15(8):1376–1386. doi: 10.1093/ecco-jcc/jjab046. Aug 2PMID: 33721882; PMCID: PMC7989537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Costantino A., Noviello D., Conforti F.S., Aloi M., Armuzzi A., Bossa F., et al. COVID-19 vaccination willingness and hesitancy in patients with inflammatory bowel diseases: analysis of determinants in a national survey of the Italian IBD patients’ association. Inflamm Bowel Dis. 2022;28(3):474–478. doi: 10.1093/ibd/izab172. Jul 14Epub ahead of print. PMID:34259844; PMCID: PMC8344425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Crispino F., Brinch D., Carrozza L., Cappello M. Acceptance of SARS-CoV-2 vaccination among a cohort of IBD patients from Southern Italy: a cross-sectional survey. Inflamm Bowel Dis. 2021;27(11):e134–e135. doi: 10.1093/ibd/izab133. Oct 20PMID: 34089256; PMCID: PMC8195093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Dai C., Jiang M., Huang Y.H. COVID-19 vaccination in patients with inflammatory bowel disease: a survey from China. Dig Dis Sci. 2021:1–3. doi: 10.1007/s10620-021-07169-x. Aug 19Epub ahead of print. PMID: 34410574; PMCID: PMC8375283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Menni C., Klaser K., May A., Polidori L., Capdevila J., Louca P., Sudre C.H., Nguyen L.H., Drew D.A., Merino J., Hu C., Selvachandran S., Antonelli M., Murray B., Canas L.S., Molteni E., Graham M.S., Modat M., Joshi A.D., Mangino M., Hammers A., Goodman A.L., Chan A.T., Wolf J., Steves C.J., Valdes A.M., Ourselin S., Spector T.D. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID symptom study app in the UK: a prospective observational study. Lancet Infect Dis. 2021;21(7):939–949. doi: 10.1016/S1473-3099(21)00224-3. JulEpub 2021 Apr 27. PMID: 33930320; PMCID: PMC8078878. [DOI] [PMC free article] [PubMed] [Google Scholar]

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