In December 2019 the now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in Wuhan. Since then, the situation has evolved dramatically. In only a few months, the coronavirus disease (COVID-19) caused by this viral infection was declared a pandemic by the WHO, and there are currently more than 20 million confirmed cases across the globe. Since the outbreak took place, both inflammatory bowel disease (IBD) patients and practitioners have raised concerns regarding the impact of COVID-19 on patients with this condition.

Crohn’s disease (CD) and ulcerative colitis (UC), the main IBDs in humans, are chronic diseases characterized by excessive intestinal inflammation. The nature of these conditions, together with some of the drugs used to treat them, may increase the patients’ risk of developing complications and other pathologies. Particularly, IBD patients’ concerns revolve around two questions: the risk of infection and how their IBD treatments can influence the evolution of the disease.

 

Risk of suffering COVID-19 for IBD patients

For the virus to cause its effects, it must enter the human body. In the case of SARS-CoV-2 viruses, their entrance mechanisms involve a protein located on their surface, called S protein, and another one found on the host cells, called receptor ACE2. When this receptor recognizes an S protein, the two structures come together like the pieces of a puzzle, allowing the virus to enter the host cell. Therefore, we could say that SARS-CoV-2 can only infect those cells that present the ACE2 receptor on their surface. The cells located in the lungs, called pneumocytes, are a good example of this, possibly explaining the frequent respiratory symptoms in affected patients. However, ACE2 receptors can also be found in intestinal epithelial cells. Some studies revealed higher ACE2 presence in inflamed IBD intestinal samples as compared with healthy donors, so this could mean that IBD patients may be more susceptible to SARS-CoV-2 infection.

In addition, there is another agent that could increase this risk. A third kind of protein called trypsin-like protease is responsible for activating S proteins, so it plays a key role in the infection process. As the trypsin-like proteases are produced in greater quantities by intestinal cells in IBD, this factor may facilitate SARS-CoV-2 infection in patients with the condition.

However, while all these findings point to an increased risk of COVID-19 infection for IBD patients, things are not that simple. There are two distinct forms of ACE2: the full-length ACE2, which acts as a receptor for the S protein of SARS-CoV-2 and is located on the cell surface, and the soluble form of ACE2 which circulates in the blood. In vitro studies have shown that the soluble form of ACE2 might prevent the virus binding to the full-length ACE2, thus hindering infection. Notably, the soluble ACE2 levels are higher in the blood of IBD patients when compared to healthy donors. This raises the possibility that this soluble ACE2 may contribute to limit SARS-CoV-2 infection.

 

Interaction between IBD treatments and COVID-19

How IBD therapies may be linked to SARS-CoV-2 is still being studied. Many IBD patients take immunosuppressors for preventing inflammation and other IBD-associated complications. Commonly, these drugs are associated with an increased risk of infection, as they block some processes needed for the immune system to fight pathogens like the virus that causes the COVID-19 disease. On the other hand, theoretically, certain immunosuppressive medications may also have beneficial effects for COVID-19 patients, since one of the causes of death in COVID-19 is the cytokine storm, an uncontrolled release of molecules by the immune cells which triggers excessive inflammation that may end up in acute respiratory distress syndrome and multiorgan failure.

Overall, while the risk of IBD therapies appears to be limited, practitioners still have to engage in a careful discussion regarding how IBD medications may affect COVID-19 disease. Besides the effect of IBD drugs, there are other factors to consider. On the one hand, interrupting an IBD treatment may lead to IBD relapse, which frequently requires hospitalisation and therefore greater COVID-19 exposure. And, if a patient gets infected as a result of this, it may also impact their IBD state, as there may be undesired interactions between COVID-19 and IBD treatments.

 

In summary, there is not enough evidence to state that COVID-19 occurs more frequently in IBD patients than in the general population. Older patients with IBD who also endure other conditions may be at higher risk, as well as patients suffering from malnutrition. Furthermore, depending on the local situation, there could be an increased risk of COVID-19 infection during IBD surgery at hospitals.

Regarding the effect of IBD treatments on COVID-19, further studies are also required. There is not enough evidence to make patients with IBD discontinue their IBD medications. However, there are some studies that show that some COVID-19 treatments may cause undesired interactions with IBD therapies, altering their therapeutic effect. So, as you can see, there is still a long way to go to fully understand how these diseases interact and affect patients overall.