Subsequently, viral particle buds and virion-containing vesicles that are released from infected cells and enable the dissemination of infection are generated 20. Upon cell entry of the virus via interactions with ACE2 and TMPRSS2, the RNA of SARS-CoV-2 reaches the cytoplasm of infected cells, resulting in the generation of accessory and structural proteins. In addition to ACE2, the cell surface-associated transmembrane serine protease 2 (TMPRSS2) controls cleavage and activation of the S protein and thereby regulates viral uptake 9, 19. A high expression of ACE2 is noted in type 2 pneumocytes in the lung 15, 16, 19, which explains the preference of SARS-CoV-2 infection for the airways. Moreover, ACE2 is involved in the expression of antimicrobial peptides and the ecology of the gut microbiota 17.
This monocarboxypeptidase regulates the cleavage of several peptides within the renin-angiotensin system and is involved in regulation of the intestinal amino acid transporter B0AT1, whose activity controls tryptophan homeostasis. The surface spike glycoprotein (S protein) of SARS-CoV-2 enters human cells via a specific surface receptor, angiotensin-converting enzyme 2 (ACE2) 14– 18. Genetic studies indicate that SARS-CoV-2 took advantage of specific mutations and recombination events in the membrane, envelope, nucleocapsid and spike glycoprotein regions to become a novel infectious agent and to adapt to a human host 8. Mortality is substantially related to cofactors such as age, environmental factors such as smoking and comorbidities such as diabetes, hypertension, or lung and heart diseases 12.ĭetailed studies of SARS-CoV-2 by sequencing analyses revealed a close relationship to two previously known bat-derived SARS-like coronaviruses 13. Pulmonary infection can be followed by acute respiratory distress syndrome and multiorgan failure, thereby contributing to the marked mortality in patients with SARS-CoV-2 infection 2, 10, 11. Although many patients have mild flu-like symptoms, some patients develop severe disease frequently associated with the clinical manifestation of pneumonia. Initial studies demonstrated active infection of the upper and lower airways with SARS-CoV-2 (refs 1– 9). The coronavirus disease 2019 (COVID-19) pandemic is a serious global health threat caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with more than 179 million cases and 3.8 million confirmed deaths worldwide as of 24 June 2021 (see Related links). Finally, the use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines for the prevention of infection in patients with gastrointestinal diseases and concomitant immunosuppressive or biologic therapy will be discussed. In particular, the roles of corticosteroids, classic immunosuppressive agents (such as thiopurines and mycophenolate mofetil), small molecules (such as Janus kinase (JAK) inhibitors), and biologic agents (such as tumour necrosis factor (TNF) blockers, vedolizumab and ustekinumab) are reviewed. In this Review, data on the use of such therapies are discussed with a primary focus on inflammatory bowel disease, autoimmune hepatitis and liver transplantation. These findings lead to the question of whether immunosuppressive and biologic therapies for gastrointestinal diseases affect the incidence or prognosis of COVID-19 and, thus, whether they should be adjusted to prevent or affect the course of the disease. Importantly, the activation of cytotoxic follicular helper T cells and a reduction of regulatory T cells have a crucial, negative prognostic role. Although triggering of anti-viral immune responses is essential for clearance of infection, some patients have severe lung inflammation and multiorgan failure due to marked immune cell dysregulation and cytokine storm syndrome. The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health crisis causing major challenges for clinical care in patients with gastrointestinal diseases.
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