COVID-19 and immunomodulation in IBD

Abstract

The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.

Keywords: cytokines; inflammation; inflammatory bowel disease.

Figure 1

Hypothetical pathogenesis of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infects ACE2 expressing epithelial cells in the lung and/or the intestine. This is followed by production of mediators causing immune cell activation. Overwhelming immune cell activation may lead to severe complications including acute respiratory distress syndrome (ARDS), shock and kidney or multiorgan failure. B, B lymphocytes; IEC, intestinal epithelial cell; ILC, innate lymphoid cell; M, monocyte/macrophage; N, neutrophils; Teff, effector T cells; Treg, regulatory T cell; Type I P, type I pneumocytes; Type II P, type II pneumocytes.

Figure 2

The ACE/ACE2 receptor system (modified according to Zhang et al 52). The classical renin-angiotensin-aldosterone system ACE/angiotensin II/angiotensin type 1/2 receptor (AT1-R) and ACE2/Ang 1–7/MAS-1 receptor (MAS1-R) systems are shown. The ACE/AT1-R system has been mainly implicated in pro-inflammatory immune responses and tissue injury. In contrast, the ACE2/MasR system appears to play a key role in many anti-inflammatory pathways controlling tissue protection.

Figure 3

COVID-19 pneumonia in a medical doctor without known comorbidities detected by chest CT imaging. Two representative images demonstrating ground-glass opacities with consolidations are shown.