Gastrointestinal and renal complications in SARS-CoV-2-infected patients: Role of immune system

Abstract

The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease has been accompanied by various gastrointestinal (GI) and renal manifestations in significant portion of infected patients. Beside studies on the respiratory complications of coronavirus infection, understanding the essential immunological processes underlying the different clinical manifestations of virus infection is crucial for the identification and development of effective therapies. In addition to the respiratory tract, the digestive and urinary systems are the major sources of virus transmission. Thus, knowledge about the invasion mechanisms of SARS-CoV-2 in these systems and the immune system responses is important for implementing the infection prevention strategies. This article presents an overview of the gut and renal complications in SARS-CoV-2 infection. We focus on how SARS-CoV-2 interacts with the immune system and the consequent contribution of immune system, gut, and renal dysfunctions in the development of disease.

Keywords: SARS-CoV-2; antiviral immunity; gastrointestinal tract; kidney.

FIGURE 1

Immune system responses to SARS‐CoV‐2 invasion: Viral exposure, production of pro‐inflammatory cytokines, recruitment of immune cells, and differentiation of B cells to plasma cells and antibody production, phagocytosis of antigens results in differentiation of T and B cells and antibody production. ACE2, angiotensin‐converting enzyme 2; DC, dendritic cell; IgA, immunoglobulin A; MQ, macrophage; Th, T helper cell; Treg, T regulatory cell

FIGURE 2

The immune system in GI tract: The GI mucosal immune system consists of epithelium, lamina propria and gut‐associated lymphoid tissue. DCs uptake antigens and migrate to the LP, secondary lymphoid tissue and draining lymph nodes. M cells in the epithelium of Peyer's patches pass the antigens to DCs, macrophages and other APCs. Naive T cells become activated in secondary lymphoid tissues. DC, dendritic cell; IgA, immunoglobulin A; M cell, microfold cell; MQ, macrophage

FIGURE 3

SARS‐CoV‐2 and diarrhoea: Water and electrolytes transport across the endothelial cells in: I, normal condition; II, severe infectious diarrhoea; III, SARS‐CoV‐2 infection: suppression of inflammatory cells (cytotoxic T cells and type 1 macrophages) by anti‐inflammatory cells (Treg cells and type 2 macrophages) reduces distribution of intestinal water and electrolytes transport and barrier functions. DC, dendritic cell; MQ, macrophage; Treg, T regulatory cell

FIGURE 4

SARS‐CoV‐2 and IBD: I, in normal condition, high expression of ACE2 on the epithelial cells increases binding of SARS‐CoV‐2 to the gut epithelial cells, and induces production of inflammatory cytokines. II, In IBD patients, shedding ACE2 (soluble ACE2) from inflamed cells decreases and inhibits virus attachment to the epithelial cells, and reduces production of inflammatory cytokines. III, Medication of IBD by immunosuppressive drugs (IS) or anti‐inflammatory drugs (AI) might decrease soluble ACE2 while inhibit induced inflammation in IBD patients with SARS‐COV‐2 infection. ACE2, angiotensin‐converting enzyme 2; AI, anti‐inflammatory medicine; IBD, inflammatory bowel disease; IS: immunosuppressive medicine

FIGURE 5

SARS‐CoV‐2 and cancer: Radiation therapy and chemotherapy suppress inflammatory cells production which predisposes CRC patients for SARS‐CoV‐2 infection. DC, dendritic cell; MQ, macrophage; Treg, T regulatory cell

FIGURE 6

SARS‐CoV‐2 and acute kidney injury: Immune system responses against SARS‐CoV‐2 and cytopathic effect of SARS‐CoV‐2 may cause acute kidney injury