Gastrointestinal symptoms, pathophysiology, and treatment in COVID-19

Abstract

The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged and is responsible for the Coronavirus Disease 2019 global pandemic. Coronaviruses, including SARS-CoV-2, are strongly associated with respiratory symptoms during infection, but gastrointestinal symptoms, such as diarrhea, vomiting, nausea, and abdominal pain, have been identified in subsets of COVID-19 patients. This article focuses on gastrointestinal symptoms and pathophysiology in COVID-19 disease. Evidence suggests that the gastrointestinal tract could be a viral target for SARS-CoV-2 infection. Not only is the SARS-CoV-2 receptor ACE2 highly expressed in the GI tract and is associated with digestive symptoms, but bleeding and inflammation are observed in the intestine of COVID-19 patients. We further systemically summarize the correlation between COVID-19 disease, gastrointestinal symptoms and intestinal microbiota. The potential oral-fecal transmission of COVID-19 was supported by viral RNA and live virus detection in the feces of COVID-19 patients. Additionally, the viral balance in the GI tract could be disordered during SARS-CoV-2 infection which could further impact the homeostasis of the gut microbial flora. Finally, we discuss the clinical and ongoing trials of treatments/therapies, including antiviral drugs, plasma transfusion and immunoglobulins, and diet supplementations for COVID-19. By reviewing the pathogenesis of SARS-CoV-2 virus, and understanding the correlation among COVID-19, inflammation, intestinal microbiota, and lung microbiota, we provide perspective in prevention and control, as well as diagnosis and treatment of the COVID-19 disease.

Keywords: ACE-2; COVID-19; Cytokine; GI symptoms; Inflammation; Microbiota; SARS-CoV-2; Vitamin D.

Figure 1

The lifecycle of SARS-CoV-2 in host epithelial cells. The spike protein of SARS-Cov-2 binds to the ACE2 receptor. The virus entry into host epithelial cells is mediated by the TMPRSS2 receptor. After entry, viral genomic RNA is uncoated into the cytoplasm. After translation, polypeptides pp1a and pp1ab are produced and then cleaved by viral proteases to form non-structural proteins, RNA-dependent RNA polymerase and helicase which form a replicase-transcriptase complex with the viral gRNA. This complex localizes to intracellular doubled membrane vesicles where it mediates production of (−) sense RNA through replication and transcription. During replication, full length (−) RNA copies of the genome are produced and used as templates for full length (+) RNA. Sub genomic RNAs are produced through transcription and are translated into structural proteins, nucleocapsid (N), spike (S), membrane (M) and envelope (E). Spike, membrane and envelope proteins enter the endoplasmic reticulum while the nucleocapsid forms the nucleoprotein complex with newly synthesized (+) gRNA. They are assembled into a virus particle in the endoplasmic reticulum Golgi-intermediate compartment and are excreted through the Golgi apparatus and are finally released by exocytosis in small vesicles.

Figure 2

The infection of SARS-CoV-2 is determined by multiple factors, including environmental factors, genetic factors, and immunity.

Figure 3

COVID-19 can affect multiple systems in the body with devastating consequences. In COVID-19 patients, lungs are ground zero, but the SARS-CoV-2 virus can extend to many organs including the heart and blood vessels, kidneys, brain, liver, and gastrointestinal tract. The presence of SARS-CoV-2 virus in the GI tract, stool, and saliva raises the unsettling possibility of oral-fecal transmission of COVID-19. Additionally, as the intestinal microbiota plays an important role in immune system and lung health, the gut-lung axis may play a part in COVID-19 disease progression. However, it needs more painstaking research and clinical data to sharpen the picture of the reach of SARS-CoV-2 and the cascade of effects in the body's complex and interconnected systems.