Inflammatory bowel disease (IBD) and the therapies used to treat it do not increase a patient’s risk of infection by COVID-19, according to a study by researchers at the University of Miami Miller School of Medicine.
“When the COVID-19 epidemic began, there was a lot of concern among patients and their treating physicians about whether patients who had IBD would be particularly susceptible to COVID-19, either as a result of having intestinal inflammation or as a result of the medications that they were taking,” said study senior author Maria T. Abreu, M.D., director of the Crohn's & Colitis Center, professor of medicine and professor of microbiology and immunology at the Miller School. The study was published online in IBD Journal.
Building on what is known about how similar viruses enter cells of the body, Dr. Abreu, lead author Juan F. Burgueno, D.V.M., Ph.D., and their colleagues hypothesized that receptors in the lung involved in novel coronavirus infection could also be present in the gut and participate in virus infection through this route.
“Right around the time that we did this study, there were reports coming out of China and elsewhere that the gastrointestinal tract might express the receptors that are important for uptake of the virus,” Dr. Abreu said. That raised the question if the small and large intestine might serve as secondary sites of infection for the novel coronavirus, after the lungs.
Specifically, in the first of two steps, the angiotensin I converting enzyme 2 (ACE2) receptor allows the crown-like spikes of the virus to attach to cells. Next, the host transmembrane serine protease 2 (TMPRSS2) cleaves the spikes, exposing a spike protein subunit that mediates the entrance in the cell.
To learn more, the investigators examined the intestines of mice and found the ACE2 receptor and TMPRSS2 viral entry molecule highly expressed in the diverse segments of the intestine. Further, in a mouse model that mimics the inflammation associated with human colitis, they did not find any increase in the presence of ACE2 or TMPRSS2.
“We thus decided to look at whether in the gastrointestinal tract of patients with Crohn's disease and ulcerative colitis the receptors for viral entry were present, and whether the level of expression was higher or lower in these patients with inflammation,” said Dr. Abreu, who is also chair of the International Organization for the Study of Inflammatory Bowel Disease.
Using stored biopsy samples of 65 people with IBD from previous studies at the Miller School, they confirmed presence of ACE2 and TMPRSS2 in the ileum and colon, the portions of the intestine typically affected by IBD. Patients who had intestinal inflammation at the time samples were taken did not express heightened amounts of these viral entry molecules when compared with non-inflamed patients.
The investigators also mined publicly available databases to examine the gene expression associated with ACE2 and TMRPSS2 in samples taken from the edge of inflamed ulcers in another group of 105 patients with IBD. This confirmed that intestinal inflammation was not associated with a greater likelihood of coronavirus infection.
After ruling out a likely role for IBD itself in heightened risk for viral infection, including during times of inflammation, they turned to medications used to treat Crohn’s disease and ulcerative colitis. The goal was to determine if therapy that alters the immune system could expose IBD patients to additional risk.
“We went on to look at the relationship to medications and found that some of the most common medications used by IBD patients, in particular anti-tumor necrosis factor (TNF) antibodies, decreased the levels of expression of these receptors,” Dr. Abreu said. “Thus the effect of anti-TNFs could in theory be protective.”
“All told, our study gives people a measure of reassurance that IBD alone or on medications does not seem to increase the expression of these receptors and thus is unlikely to increase the susceptibility to infection with the virus.”
Dr. Abreu added, “This leads us to think that our study – even though it was done in patient samples and not in people who were infected with COVID-19 – does translate to real life, and that our patients are not more susceptible to infection with this virus.
“This gives us plenty of opportunity to offer reassurance to our patients and our gastroenterology colleagues.”
The study was possible through a long-standing collaboration with the Biostatistics and Bioinformatics Shared Resource (BBSR) at Sylvester Comprehensive Cancer Center, directed by Xi Steven Chen, Ph.D., associate professor of biostatistics at the Miller School, along with essential input from Lily Wang, Ph.D. (BBSR), and Adrian Reich, Ph.D., bioinformatician at the Scripps Research Institute in Jupiter, Florida.
The National Institute of Diabetes and Digestive and Kidney Diseases, Takeda Pharmaceutical, USA, Pfizer-ASPIRE, The Micky & Madeleine Arison Family Foundation Crohn's & Colitis Discovery Laboratory, and the Martin Kalser Chair to Dr. Maria Abreu provided funding to support the study.