Clinical Pearls

The Foundation's Clinical Pearls is a series of summaries of the most clinically useful material designed to help implement evidence-based care. These brief summaries of free-standing, clinically relevant information are based on the best available evidence and experts' clinical knowledge and experience. They are part of the vast domain of evidence-based medicine and can be helpful in dealing with clinical problems.

Clinical Pearls aims to provide practical information to assist healthcare providers with commonly encountered complications of inflammatory bowel diseases (IBD), extra-intestinal manifestations of IBD, and complications arising from both the medical and surgical treatments of IBD. Clinical Pearls is produced monthly by members of the Professional Education Committee, a subset of the National Scientific Advisory Board. See our featured Clinical Pearl below, or browse past works.

 

 

Introduction

Coronavirus disease 2019 (COVID-19) has significantly affected the care of our patients. As we are learning about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact in patients with inflammatory bowel disease (IBD), several questions have come up. Are patients with IBD at increased risk of SARS-CoV-2 infection? How does COVID-19 present in these patients, and are they at increased risk of complications? 

Are patients with IBD at increased risk of COVID-19?

There is currently no evidence that patients with IBD are at increased risk of SARS-CoV-2 infection.(1) Similar infection rates in patients with and without IBD have been reported in studies out of the US, Europe and Asia.(2-5) In particular, anti-tumor necrosis factor (anti-TNF) agents and thiopurines have not been found to increase the risk of COVID-19.(2) 

However, in a study out of NYC, although patients with IBD were not at increased risk of infection overall, moderate to severe disease activity and corticosteroids were associated with increased rates of SARS-CoV-2 infection among patients with IBD.(6)

How does COVID-19 affect patients with IBD and their care?

COVID-19 may present differently in patients with IBD.(1) Patients with IBD who develop SARS-CoV-2 infection have symptoms of abdominal pain and diarrhea more frequently than patients without IBD.(6, 7) COVID-19 may also mimic disease flares.(1, 6) Among patients with IBD, COVID-19 is not only associated with increased rates of GI symptoms, but also an increased risk of elevated inflammatory markers and endoscopically active disease compared to patients without COVID-19.(6) Of note, fecal calprotectin as well can be increased in the setting of COVID-19 diarrhea, even in patients without IBD.(8)

The COVID-19 pandemic itself has also had a significant impact on the care of patients with IBD.(9) In addition to a change in the delivery of care with a transition to telemedicine and reduced access to endoscopy,(9) non-adherence to infusible biologics has increased by 70%.(10) In a nationwide VA cohort, up to a quarter of patients were found to have intervals of more than 10 weeks between infusions.(10)

Do patients with IBD have worse outcomes with COVID-19?

Several studies have assessed COVID-19 outcomes among patients with IBD,(11) including the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry.(12) This international collaborative effort has helped gather data on 2,156 patients with IBD and COVID-19 as of August 25, 2020.(12) According to available data thus far, COVID-19 does not seem to be associated with worse outcomes in patients with IBD.(13-16) In particular, biologics have not been associated with an increased risk of COVID-19 complications in several studies, including in an analysis of the first 525 cases of the SECURE-IBD registry.(13-15) 

In fact, biologics including janus kinase (JAK) inhibitors and anti-TNFs (e.g. infliximab, adalimumab) are being evaluated as possible therapies for COVID-19 in clinical trials.(17) In addition, 2 case reports have described the use of infliximab to treat both severe IBD and COVID-19 with promising results.(18, 19)

Risk factors for severe COVID-19 

Although patients with IBD are not at increased risk of COVID-19 complications compared with the general population, several risk factors have been associated with more severe outcomes in IBD.(13, 14) Data from the SECURE-IBD registry have found corticosteroid use, the presence of 2 or more comorbidities, and older age to be associated with more severe COVID-19.(20) Although 5-aminosalicylate (5-ASA) was also found to be a risk factor, it is currently unclear whether this is due to confounding or a true association.(13) Additionally, an Italian study found active disease to be associated with worse outcomes in patients with IBD, including increased rates of hospitalization and death.(14)

Managing IBD in the setting of COVID-19

Several societies have proposed detailed recommendations for the management of patients with IBD in the setting of SARS-CoV-2 infection, including the International Organization for the Study of Inflammatory Bowel Disease (IOIBD), the British Society of Gastroenterology (BSG) and others.(21-23) Given the limited data available, most of these recommendations are based on expert opinion and are subject to change as we are learning more about COVID-19 and its impact on IBD.

If not infected with SARS-CoV-2, patients are generally recommended to continue IBD therapies except for corticosteroids, which should preferably be tapered or stopped.(21, 22) 

In the case of SARS-CoV-2 infection, current guidance recommends to hold immunosuppressive medications until resolution of COVID-19 (at least 10 days after symptom onset and at least 3 days after recovery according to IOIBD recommendations).(21, 22, 24) A detailed list of recommendations on several aspects of management can be found on the IOIBD website.(25)

Summary

Patients with IBD do not appear to be at increased risk of SARS-CoV-2 infection. However, corticosteroid use and active disease may increase the risk of COVID-19 in this setting.  In addition, although patients with IBD have similar COVID-19 outcomes compared with the general population, several risk factors for severe COVID-19 have been identified and include corticosteroid use, older age, comorbidities, active IBD and possibly 5-ASA use. Several societies have proposed expert recommendations to help guide the management of patients with IBD in the context of COVID-19. These may change as we are learning more about SARS-CoV-2 and how it affects patients with IBD. Clinicians are encouraged to report all cases of COVID-19 in their patients with IBD to the SECURE-IBD registry in order to help improve our understanding of COVID-19 and its impact on our patients. 

 

References

1. El Ouali S, Philpott J, Vargo J, Regueiro M. COVID-19 in patients with IBD and pancreaticobiliary disorders. Cleveland Clinic Journal of Medicine. 2020.

2. Khan N, Patel D, Xie D, Lewis J, Trivedi C, Yang Y-X. Impact of Anti-TNF and Thiopurines medications on the development of COVID-19 in patients with inflammatory bowel disease: A Nationwide VA cohort study. Gastroenterology. 2020.

3. Allocca M, Fiorino G, Zallot C, Furfaro F, Gilardi D, Radice S, et al. Incidence and Patterns of COVID-19 Among Inflammatory Bowel Disease Patients From the Nancy and Milan Cohorts. Clinical Gastroenterology and Hepatology.

4. Taxonera C, Sagastagoitia I, Alba C, Mañas N, Olivares D, Rey E. 2019 novel coronavirus disease (COVID-19) in patients with inflammatory bowel diseases. Alimentary pharmacology & therapeutics. 2020;52(2):276-83.

5. Mak JWY, Weng M-T, Wei SC, Ng SC. Zero COVID-19 infection in inflammatory bowel disease patients: Findings from population-based inflammatory bowel disease registries in Hong Kong and Taiwan. Journal of Gastroenterology and Hepatology.n/a(n/a).

6. Lukin DJ, Kumar A, Hajifathalian K, Sharaiha RZ, Scherl EJ, Longman RS, et al. Baseline Disease Activity and Steroid Therapy Stratify Risk of COVID-19 in Patients with Inflammatory Bowel Disease. Gastroenterology. 2020:S0016-5085(20)34738-7.

7. D’Amico F, Danese S, Peyrin-Biroulet L. Systematic review on IBD patients with COVID-19: it is time to take stock. Clinical Gastroenterology and Hepatology.

8. Effenberger M, Grabherr F, Mayr L, Schwaerzler J, Nairz M, Seifert M, et al. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut. 2020:gutjnl-2020-321388.

9. Kennedy NA, Hansen R, Younge L, Mawdsley J, Beattie RM, Din S, et al. Organisational changes and challenges for inflammatory bowel disease services in the UK during the COVID-19 pandemic. Frontline Gastroenterology. 2020;11(5):343-50.

10. Khan N, Patel D, Xie D, Pernes T, Lewis J, Yang Y-X. Adherence of infusible biologics during the time of COVID-19 among patients with Inflammatory Bowel Disease: A nationwide VA cohort study. Gastroenterology. 2020.

11. Aziz M, Fatima R, Haghbin H, Lee-Smith W, Nawras A. The Incidence and Outcomes of COVID-19 in IBD Patients: A Rapid Review and Meta-analysis. Inflammatory Bowel Diseases. 2020.

12. Brenner EJ UR, Colombel JF, Kappelman MD.  . SECURE-IBD Database Public Data Update.  [Available from: covidibd.org.

13. Brenner EJ, Ungaro RC, Gearry RB, Kaplan GG, Kissous-Hunt M, Lewis JD, et al. Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry. Gastroenterology. 2020.

14. Bezzio C, Saibeni S, Variola A, Allocca M, Massari A, Gerardi V, et al. Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study. Gut. 2020;69(7):1213-7.

15. Haberman R, Axelrad J, Chen A, Castillo R, Yan D, Izmirly P, et al. Covid-19 in Immune-Mediated Inflammatory Diseases — Case Series from New York. New England Journal of Medicine. 2020;383(1):85-8.

16. Papa A, Gasbarrini A, Tursi A. Epidemiology and the Impact of Therapies on the Outcome of COVID-19 in Patients With Inflammatory Bowel Disease. Am J Gastroenterol. 2020.

17. Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs. 2020.

18. Dolinger MT, Person H, Smith R, Jarchin L, Pittman N, Dubinsky MC, et al. Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab. J Pediatr Gastroenterol Nutr. 2020:10.1097/MPG.0000000000002809.

19. Bezzio C, Manes G, Bini F, Pellegrini L, Saibeni S. Infliximab for severe ulcerative colitis and subsequent SARS-CoV-2 pneumonia: a stone for two birds. Gut. 2020:gutjnl-2020-321760.

20. Aloysius MM, Thatti A, Gupta A, Sharma N, Bansal P, Goyal H. COVID-19 presenting as acute pancreatitis. Pancreatology. 2020.

21. Grossberg LB, Pellish RS, Cheifetz AS, Feuerstein JD. Review of Societal Recommendations Regarding Management of Patients With Inflammatory Bowel Disease During the SARS-CoV-2 Pandemic. Inflammatory bowel diseases. 2020:izaa174.

22. Rubin DT, Abreu MT, Rai V, Siegel CA, International Organization for the Study of Inflammatory Bowel D. Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting. Gastroenterology. 2020:S0016-5085(20)30465-0.

23. Kennedy NA, Jones G-R, Lamb CA, Appleby R, Arnott I, Beattie RM, et al. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic. Gut. 2020;69(6):984-90.

24. IOIBD. IOIBD Recommendations: Best practice guidance for when to restart IBD therapy in patients who have had confirmed or suspected COVID 19.

25. IOIBD. IOIBD COVID-19 and IBD Guidelines.