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.

Impact of Corticosteroids and Immunosuppressive Therapies on Symptomatic SARS-CoV-2 Infection in a Large Cohort of Patients with Chronic Inflammatory Arthritis

“…Accordingly, immunomodulating agents are currently being trialed in the treatment of SARS-CoV-2 infection [12][13][14][15]. However, concern remains on the possible impact of these same immunosuppressive therapies on increasing the risk of COVID-19 or worsening its clinical course in patients on chronic treatment for immune-mediated in ammatory diseases (IMIDs) [16][17][18][19]. Due to a general impairment of the immune system, IMIDs per se are characterized by an intrinsic increased infectious risk [20][21][22].…”

Addendum zu den S3-Leitlinien Morbus Crohn und Colitis ulcerosa: Betreuung von Patienten mit chronisch entzündlichen Darmerkrankungen in der COVID-19-Pandemie – offene Fragen und Antworten

“…Für Vedolizumab [117] und Ustekinumab konnte bei CED-Patienten keine erhöhte Rate viraler Infektionen beobachtet werden. Es wird spekuliert, dass die Il-23-Blockade durch Ustekinumab bei COVID-19 die pathogene Th17-Antwort im Rahmen eines Zytokinsturms unterdrückt [94]. Wie oben angeführt, weist das IO IBD-Register für Patienten mit einer systemischen Steroidtherapie die höchste Mortalität im Vergleich zu Patienten aus, die mit Biologika behandelt werden.…”

“…Die bisherigen Daten der Secure-IBD-Studie ergeben bisher auch keine Hinweise auf ein erhöhtes Risiko eines ungünstigen Verlaufs einer COVID-19-Erkrankung (Intensivbehandlung, Mortalität) unter einer Therapie mit TNF-Antikörpern, Ustekinumab und Vedolizumab. TNF-Antikörper könnten sogar möglicherweise eine Verminderung des pulmonalen Organschadens bewirken[94]. Dieser Effekt wird vermutlich durch ein verringertes "Shedding" der ACE2-Ektodomäne ausgelöst, das über TNFα-Converting-Enzyme vermittelt wird.…”

“…Die ACE2-Ektodomänen spielen eine wesentliche Rolle für das Eindringen von SARS-CoV-2 in die Zellen. Da hohe IFN-γ-und TNF-α-Spiegel mit schweren Verläufen einer SARS-CoV-Infektion assoziiert sind, wird eine Blockade von TNF als mögliche Option zur Behandlung dieses Zytokin-Release-Syndroms bei einigen Patienten postuliert[94].…”

COVID-19: Don’t Neglect the Gastrointestinal Tract!

“…Patients with chronic inflammatory bowel disease and other autoimmune diseases in the digestive system belong to the high-risk group for COVID-19 as these patients are often on immune-suppressive or immune-modulatory treatment. The pathophysiological impact of the infection and the cellular interaction of the virus with the intestinal mucosa have recently been reviewed elsewhere [5].…”