Individuals diagnosed with Crohn’s Disease and Ulcerative Colitis, the most common inflammatory bowel diseases (IBD), may be more susceptible to infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes the coronavirus disease COVID-19.
This article provides insight into the current opinion regarding the implications of COVID-19 for IBD patients, covering both the relevance of immunosuppressive medications and the possible inflammatory effect of infection on the gastrointestinal tract and featuring comments by Professor of Gastroenterology at the University of Rome Tor Vergata Dr. Giovanni Monteleone, MD, PhD.
- COVID-19 and the Gastrointestinal System
- Are Crohn’s Disease and Ulcerative Colitis patients at greater risk for developing COVID-19?
- Should inflammatory bowel disease patients continue taking immunosuppressive medications during the coronavirus pandemic?
- ECCO, CCFA, IOIBD, Crohn’s and Colitis UK Recommendations
COVID-19 and the Gastrointestinal System
COVID-19 is known to involve the gastrointestinal tract. An analysis of 1,099 patients with laboratory-confirmed SARS-CoV-2 infection in China found that 3.8% of patients experienced diarrhea and 5.0% had nausea or vomiting. In addition, the virus has been identified in stool samples from individuals infected by the virus.
One study identified viral RNA in the stool of over 50% of patients and found that, even after testing negative for SARS-CoV-2 in respiratory samples, over 20% of patients tested positive for the virus in stool samples, suggesting that the virus may continue to infect the gastrointestinal system even after being cleared from the lungs and airways.
Thus, the course of SARS-CoV-2 infection may commonly involve cells of the gastrointestinal tract, a finding of importance for patients with IBD.
Are Crohn’s Disease and Ulcerative Colitis patients at greater risk for developing COVID-19?
According to a recent article published in the Journal of Crohn’s and Colitis by Dr. Monteleone and Dr. Sandro Ardizzone, MD, PhD, of the University of Milan, based on the molecular characteristics of cells in their gastrointestinal tract, IBD patients could theoretically have a greater chance of contracting the virus through the fecal-oral route, but this has not been identified.
By binding to a receptor protein known as angiotensin-converting enzyme 2 (ACE 2) on the surface of human cells, the coronavirus is able to spread within the body and lead to infection. While ACE2 is normally expressed by epithelial cells throughout the body, including those of the lungs, kidneys, blood vessels, and intestines, the concentration of the receptor protein is particularly high among epithelial cells of the colon and the final portion of the small intestine, known as the terminal ileum.
Levels of ACE2 are thought to be increased in the gut of patients with IBD, and significantly more elevated in individuals with Crohn’s Disease than those with Ulcerative Colitis, suggesting that IBD patients with inflamed intestinal tissue may have an outlet with increased susceptibility for the virus to infect the body.
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However, Dr. Monteleone and Dr. Ardizzone found “no evidence” that Ulcerative Colitis or Crohn’s Disease patients are at greater risk for developing COVID-19. According to Dr. Monteleone, it is currently thought that IBD patients do not have a greater likelihood of acquiring the infection.
“In a time of unprecedented pressure for health services during the Covid-19 pandemic and associated concern and anxiety among patients with inflammatory bowel diseases, it is important that patients know they have no increased risk to get infected with SARS-CoV-2,” Dr. Monteleone told ImmunoFrontiers. “Nonetheless they should adopt all of the preventive measures which are known to contain virus spread, such as staying home and avoiding public gatherings.”
The authors suggested that these findings could be explained by research indicating that the peripheral blood of IBD patients contains increased levels of a soluble form of ACE2, which may “distract” virus particles from membrane-bound ACE2 present on the surface of human cells to limit the spread of the virus within the body. Indeed, other researchers have suggested that soluble ACE2 could represent a therapy for COVID-19.
According to the COVID-19 Task Force of the European Crohn’s and Colitis Organization (ECCO), COVID-19 is not known to be a cause of IBD flares, but the possibility of this phenomenon is not “unexpected” since the H1N1 virus was known to cause mild flares.
Due to the involvement of the ACE2 receptor in the pathophysiology of SARS-CoV-2 infection, recent research and discussions have considered whether relevant medications including ACE inhibitors and angiotensin receptor blockers (ARBs), which are widely used to treat cardiovascular disease, could increase susceptibility to COVID-19.
Should inflammatory bowel disease patients continue taking immunosuppressive medications during the coronavirus pandemic?
Dr. Monteleone emphasized that IBD patients should continue to take their medications but noted the importance of smoking cessation. “It is important that patients remain on their treatment regime with a view to optimising disease control. Patients must stop smoking as this seems to be a factor increasing the risk of infection.”
While particular immunosuppressive medications such as azathioprine and methotrexate could adversely affect the antiviral immune response, cytokine-blocking drugs may actually have a beneficial effect, since these therapies have been successfully used to treat the cytokine storm, a life-threatening inflammatory overreaction of the immune system characteristic of severe cases of COVID-19. Indeed, early research suggests that interleukin-6 blocking agents may be helpful for treating COVID-19 pneumonia.
Dr. Monteleone provided further information to ImmunoFrontiers. “In our opinion, the best advice for patients with IBD is to try to minimize the risk of infection by following good hand hygiene including frequently washing with soap and water, covering the mouth and nose with a tissue or your sleeve but not your hands when coughing or sneezing, avoiding close contact with anyone with influenza-like and/or upper respiratory symptoms, and staying home or isolated if possible.”
IBD patients should be cautious when using public toilets. “In addition to these measures, emerging reports state that patients might have viral RNA present in their faeces and live virus has been isolated from faecal samples. Thus, caution should be taken when using public toilets given the implications for the potential route of faecal–oral transmission,” Dr. Monteleone continued.
Moving forwards, Dr. Monteleone and his team intend to study the underlying reasons for the decreased susceptibility of particular populations to SARS-CoV-2 infection. “We are carrying on studies aimed at evaluating the mechanisms, which could reduce the risk of Covid-19, paying a lot of attention to factors prevalently expressed in categories of individuals who seem to be protected, such as children and women.”
ECCO, CCFA, IOIBD, Crohn’s and Colitis UK Recommendations
In addition to these measures, the ECCO COVID-19 Task Force suggested that IBD patients should stock medicines and transition to using self-injectable subcutaneous medications instead of infusions that require a visit to the hospital. The Task Force also indicated that patients should not cease the use of immunosuppressive medications but that, when possible and following a risk assessment, the initiation of immunosuppressive treatment for IBD patients starting therapy should be postponed.
The Crohn’s and Colitis Foundation of America (CCFA), citing the International Organization for Study of Inflammatory Bowel Disease (IOIBD), provided similar guidance regarding immunosuppressive medications, but noted the recommendations of the CDC regarding possible limitations to the use of corticosteroids such as prednisone and prednisolone. The CCFA, IOIBD, and Crohn’s and Colitis UK have not recommended pauses in the use of immunosuppressive medications.
Monteleone G, Ardizzone S. (2020) Are Patients with Inflammatory Bowel Disease at Increased Risk for Covid-19 Infection? Journal of Crohn’s and Colitis, 1–3. doi:10.1093/ecco-jcc/jjaa061