8 June 2023

The 23rd of March 2023 marked the three-year anniversary of the first UK COVID-19 lockdown. A day I and many others remember so well. It was a frightening time, with many unknowns: What impact would the pandemic have across the world? Just how deadly was this new virus? How long would the lockdowns last for? Would life be changed forever?

The impact of the pandemic was different for everyone. For patients with inflammatory bowel disease (IBD) the pandemic affected life on several fronts. Over the past three-years much has been learned.  This piece concentrates on COVID-19 risk and IBD medications.

There were initial concerns that IBD patients would be more susceptible to developing a severe response to the COVID-19 infection.(1,2) It is believed that IBD occurs due to an abnormal immune response within the body to the lining of the gut and the normal bacteria that live within it.(2,3) To control this, patients with IBD can be treated with medications aimed at dampening down this overactive immune response.

As these medical treatments are known to be associated with an increased risk of infection (because they depress people’s immune systems), there was concern that IBD patients had a higher risk of contracting COVID-19 and were more likely to develop a more severe form of the infection.(1,2,4) Internationally, it was reported that patients felt this increased risk was both due to their underlying bowel disease and their IBD medication.(5)

Understandably, the advice from the British Society of Gastroenterologists (BSG) mirrored that of the UK government. It centred around avoiding unnecessary travel, working from home if possible, good hand hygiene and to continue taking IBD medication, thus helping to avoid flares and the potential need for hospital admission.(6)

To better understand which patients were at most risk of a severe COVID-19 reaction, a patient self-assessment tool was developed by the IBD registry early in the pandemic.(7) Three separate groups of patients were identified: Those who were at low risk (same risk as the rest of UK population), those who were at moderate risk (a possible increased risk and therefore a need for enhanced social distancing), and those who were at a highest risk (and thus advised to follow government shielding guidance).(8)

The self-assessment tool was used by over 40,000 patients, helping them and their IBD teams better understand their own personal level of risk and to help guide which advice pathway to follow.(7)  For patients classed as being moderate to high risk, the psychosocial impact COVID-19 had was huge. This group of patients reported a higher level of stress and anxiety when compared to pre-pandemic levels, which persisted even after easing of the restrictions.(9)

For these patients the main factors responsible were fear of infection (for themselves or others), a lack of basic supplies, misinformation and the length of quarantine.(9) These findings have helped shine the spotlight on how important it is to ensure that all vulnerable and shielding patients have access to psychological support.(9)

The SECURE-IBD database was an international collaboration between 47 countries, created to monitor the outcome of COVID-19 infections in patients with IBD.(10) This collaborative group discovered that those who were taking a medication from a thiopurine group such as Azathioprine were at a higher risk of developing a severe response to COVID-19. Many of these patients were over the age of 50 and this highlighted the increased risk of a severe COVID-19 response in the older IBD population.

The use of medications called ‘biologics,’ however, appeared to have a far more beneficial effect. Several research studies discovered that patients on biological therapies had a far lower risk of developing a severe COVID-19 response. (2,11) It is believed that this is due to the medication reducing the number of special protein molecules (cytokines) released by the immune system.(11)

Normally cytokines play an important role in the communication of the body’s immune system, telling the immune cells to start attacking the pathogen or threat, such as the COVID-19 virus. However, when a large volume of cytokines are released into the bloodstream in one go, this is called a ‘cytokine storm’ which can have harmful effects. These can vary from very high fevers, severe inflammation, lung injury and even organ-failure.(12,13)

By dampening down the immune system, the biological medications may help prevent the occurrence of a cytokine storm and therefore protect against one of the factors leading to a severe response to COVID-19.(11)

Based on this evidence, it was reported that the use of biological medications in IBD patients who were either in remission, or on the way to remission, was safe.(6) Not only would it help prevent against some of the harmful effects of the infection, but that they would also help prevent further IBD-flares, thus avoiding the need for hospital admission and even surgery.(6)

Additionally, when biological medication is stopped and restarted, the body can develop another type of protein called an antibody, which labels the medication molecules as a threat to the body. Antibodies communicate with the immune system and direct it to attack the medication molecules, meaning the medication no longer has a beneficial effect and the patient is ‘resistant’ to it.(14) By continuing to use biological medications throughout the pandemic, it could help to reduce the number of patients who would develop this resistance, therefore meaning they still had many treatment options open for their IBD in the future.

However, it is important to remember that there could have been other reasons why those on biological therapies had far fewer severe COVID-19 reactions. For example, those on immunosuppressive medications were initially warned that COVID-19 could have a severe effect. It is possible that this group of patients could have been much more cautious about infection precautions when compared to those not on the medication. When investigated, this group would therefore have far fewer occurrences of severe COVID-19 infections, not necessarily due to the medication, but due to the extra precautions they were taking.(2)

 

  1. COVID-19 and your health [Internet]. Centers for Disease Control and Prevention. 2020 [cited 2023 Jun 5]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/your-health/index.html
  2. Tripathi K, Godoy Brewer G, Thu Nguyen M, Singh Y, Saleh Ismail M, Sauk JS, et al. COVID-19 and Outcomes in Patients With Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. Inflamm Bowel Dis. 2022 Aug 1;28(8):1265–79.
  3. Ananthakrishnan AN. Environmental risk factors for inflammatory bowel diseases: a review. Dig Dis Sci. 2015 Feb;60(2):290–8.
  4. Rubin DT, Abreu MT, Rai V, Siegel CA, International Organization for the Study of Inflammatory Bowel Disease. Management of Patients With Crohn’s Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting. Gastroenterology. 2020 Jul;159(1):6-13.e6.
  5. Graff LA, Fowler S, Jones JL, Benchimol EI, Bitton A, Huang JG, et al. Crohn’s and Colitis Canada’s 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Mental Health and Quality of Life. J Can Assoc Gastroenterol. 2021 Dec;4(Suppl 2):S46–53.
  6. 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 Jun;69(6):984–90.
  7. IBD Registry – COVID-19 risk tool [Internet]. [cited 2023 Jun 5]. Available from: https://ibdregistry.org.uk/story-of-the-covid-19-ibd-risk-tool/
  8. BSG COVID-19 Guidance on IBD patient risk groups [Internet]. www.bgs.org.uk. 2020 [cited 2023 Jun 5]. Available from: https://www.bsg.org.uk/covid-19-advice/bsg-advice-for-management-of-inflammatory-bowel-diseases-during-the-covid-19-pandemic/
  9. Harris RJ, Downey L, Smith TR, Cummings JRF, Felwick R, Gwiggner M. Life in lockdown: experiences of patients with IBD during COVID-19. BMJ Open Gastroenterol [Internet]. 2020 Nov;7(1). Available from: http://dx.doi.org/10.1136/bmjgast-2020-000541
  10. Ungaro RC, Brenner EJ, Gearry RB, Kaplan GG, Kissous-Hunt M, Lewis JD, et al. Effect of IBD medications on COVID-19 outcomes: results from an international registry. Gut. 2021 Apr;70(4):725–32.
  11. Burke KE, Kochar B, Allegretti JR, Winter RW, Lochhead P, Khalili H, et al. Immunosuppressive Therapy and Risk of COVID-19 Infection in Patients With Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2021 Jan 19;27(2):155–61.
  12. Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020 Jun 16;11:1446.
  13. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497–506.
  14. Dalal SR, Cohen RD. What to Do When Biologic Agents Are Not Working in Inflammatory Bowel Disease Patients. Gastroenterol Hepatol . 2015 Oct;11(10):657–65.