Gastrointestinal tissue as a "new" target of pollution exposure.

Airborne pollution has become a leading cause of global death in industrialized cities and the exposure to environmental pollutants has been demonstrated to have adverse effects on human health. Among the pollutants, particulate matter (PM) is one of the most toxic and although its exposure has been more commonly correlated with respiratory diseases, gastrointestinal (GI) complications have also been reported as a consequence to PM exposure. Due to its composition, PM is able to exert on intestinal mucosa both direct damaging effects, (by reaching it either via direct ingestion of contaminated food and water or indirect inhalation and consequent macrophagic mucociliary clearance) and indirect ones via generation of systemic inflammation. The relationship between respiratory and GI conditions is well described by the lung-gut axis and more recently, has become even clearer during coronavirus disease 2019 (COVID-19) pandemic, when respiratory symptoms were associated with gastrointestinal conditions. This review aims at pointing out the mechanisms and the models used to evaluate PM induced GI tract damage.

Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection.

OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.

Fluid and Electrolyte Disturbances in COVID-19 and Their Complications.

The novel coronavirus disease 2019 (COVID-19) is the cause of an acute respiratory illness which has spread around the world. The virus infects the host by binding to the angiotensin-converting enzyme 2 (ACE2) receptors. Due to the presence of ACE2 receptors in the kidneys and gastrointestinal (GI) tract, kidneys and GI tract damage arising from the virus can be seen in patients and can cause acute conditions such as acute kidney injury (AKI) and digestive problems for the patient. One of the complications of kidneys and GI involvement in COVID-19 is fluid and electrolyte disturbances. The most common ones of these disorders are hyponatremia, hypernatremia, hypokalemia, hypocalcemia, hypochloremia, hypervolemia, and hypovolemia, which if left untreated, cause many problems for patients and even increase mortality. Fluid and electrolyte disturbances are more common in hospitalized and intensive care patients. Children are also at greater risk for fluid and electrolyte disturbances complications. Therefore, clinicians should pay special attention to the fluid and electrolyte status of patients. Changes in fluid and electrolyte levels can be a good indicator of disease progression.

Implications of SARS-CoV-2 infection for neurogastroenterology.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with gastrointestinal and hepatic manifestation in up to one fifth of patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, infects gastrointestinal epithelial cells expressing angiotensin-converting enzyme 2 (ACE2) receptors triggering a cascade of events leading to mucosal and systemic inflammation. Symptomatic patients display changes in gut microbiota composition and function which may contribute to intestinal barrier dysfunction and immune activation. Evidence suggests that SARS-CoV-2 infection and related mucosal inflammation impact on the function of the enteric nervous system and the activation of sensory fibers conveying information to the central nervous system, which, may at least in part, contribute symptom generation such as vomiting and diarrhea described in COVID-19. Liver and pancreas dysfunctions have also been described as non-respiratory complications of COVID-19 and add further emphasis to the common view of SARS-CoV-2 infection as a systemic disease with multiorgan involvement. PURPOSE: The aim of this review was to highlight the current knowledge on the pathophysiology of gastrointestinal SARS-CoV-2 infection, including the crosstalk with the gut microbiota, the fecal-oral route of virus transmission, and the potential interaction of the virus with the enteric nervous system. We also review the current available data on gastrointestinal and liver manifestations, management, and outcomes of patients with COVID-19.

Liver injury in the era of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.

Lipidome is lipids regulator in gastrointestinal tract and it is a life collar in COVID-19: A review.

The term lipidome is mentioned to the total amount of the lipids inside the biological cells. The lipid enters the human gastrointestinal tract through external source and internal source. The absorption pathway of lipids in the gastrointestinal tract has many ways; the 1st way, the lipid molecules are digested in the lumen before go through the enterocytes, digested products are re-esterified into complex lipid molecules. The 2nd way, the intracellular lipids are accumulated into lipoproteins (chylomicrons) which transport lipids throughout the whole body. The lipids are re-synthesis again inside the human body where the gastrointestinal lipids are: (1) Transferred into the endoplasmic reticulum; (2) Collected as lipoproteins such as chylomicrons; or (3) Stored as lipid droplets in the cytosol. The lipids play an important role in many stages of the viral replication cycle. The specific lipid change occurs during viral infection in advanced viral replication cycle. There are 47 lipids within 11 lipid classes were significantly disturbed after viral infection. The virus connects with blood-borne lipoproteins and apolipoprotein E to change viral infectivity. The viral interest is cholesterol- and lipid raft-dependent molecules. In conclusion, lipidome is important in gastrointestinal fat absorption and coronavirus disease 2019 (COVID-19) infection so lipidome is basic in gut metabolism and in COVID-19 infection success.

COVID-19 and the gastrointestinal tract: what do we already know?

The new coronavirus disease pandemic is defining 2020, with almost 17.5 million infected individuals and 700 thousand deaths up to beginning of August. It is caused by SARS-CoV-2 and the transmission is through the respiratory tract. Those infected may be asymptomatic, present typical symptoms (fever, dry cough and dyspnea), gastrointestinal symptoms (diarrhea, nausea, vomiting and abdominal pain) and viral RNA in stools. The objective of this work was to review the literature related to the prevalence of gastrointestinal symptoms, and to check the possibility of fecal-oral transmission. We searched PubMed® database on COVID-19 and gastrointestinal tract and selected articles using the PRISMA method. We eliminated articles based on titles and abstracts, small number of patients and the mechanism of infection, leaving 14 studies. Comorbidities and laboratory alterations (elevation of hepatic aminotransferases and bilirubin) were related to worsening of the disease. The prevalence of gastrointestinal symptoms ranged from 6.8% to 61.3%, including diarrhea (8.14% to 33.7%), nausea/vomiting (1.53% to 26.4%), anorexia (12.1% to 40.0%) and abdominal pain (0% to 14.5%). The presence of viral RNA in stools was rarely tested, but positive in 0% to 48.1%. The gastrointestinal tract is affected by COVID-19, causing specific symptoms, laboratory alterations and viral presence in the feces. However, the results of prevalence and possibility of fecal-oral transmission were varied, requiring further studies for more assertive conclusions. It is important that healthcare professionals draw attention to this fact, since these changes can help make diagnosis and initiate early treatment.

Pediatric COVID-19 and Appendicitis: A Gut Reaction to SARS-CoV-2?

BACKGROUND: We describe the temporal pattern of COVID-19 admissions to a tertiary care children's hospital in central New Jersey during the SARS-CoV-2 surge, covering the time period from March 29 to July 26, 2020. METHODS: Medical charts were reviewed for the date of admission, past medical history, and demographic variables, presenting signs and symptoms, admitting laboratory values, diagnostic imaging, diagnosis, treatment modalities, and outcomes including length of stay and disease severity. RESULTS: Patients with symptomatic SARS-CoV-2 infection tended to present with pneumonia early during the study period, which coincided with the early surge in New Jersey cases. Approximately 2 weeks after the peak in reported SARS-CoV-2 cases in New Jersey, we began to see fewer pneumonia cases and an increase in admissions for Multi-Inflammatory Syndrome in Children and cases of acute appendicitis in association with a diagnosis of SARS-CoV-2 infection. CONCLUSIONS: We present a novel association of acute appendicitis in children infected with SARS-CoV-2 and postulate that it may represent a postinfectious hyperinflammatory complication of SARS-CoV-2 infection occurring 2 weeks after the early manifestation of acute pneumonia disease in children.

COVID-19: Current Understanding of Pathophysiology.

Coronavirus disease 2019 has emerged as a global pandemic, affecting millions of people across the globe. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the human cell after binding to the Angiotensin-Converting Enzyme 2 receptors, that are present in various organs. The involvement of the respiratory system is common and may progress to acute respiratory distress syndrome. Besides the involvement of respiratory system other systems like cardiovascular, renal, gastrointestinal and central nervous are not uncommon. In-depth understanding of the pathophysiological basis of organs and systems involvement and disease progression aids in the safe and effective management of the COVID-19 patients. It also helps to guide future well-designed clinical trials, which is the need of time. This review aims to explore the current understanding of pathophysiological basis of various organ system involvement in patients with COVID-19, that can have relevance for patient management and future research. We reviewed the articles in various databases to assemble the current evidences. Keywords: Coronavirus disease 2019; COVID-19; pathophysiology; severe acute respiratory syndrome coronavirus 2.

Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis.

BACKGROUND: Many case series on Corona Virus Disease (COVID-19) have reported gastrointestinal (GI) and hepatic manifestations in a proportion of cases; however, the data is conflicting. The relationship of GI and hepatic involvement with severe clinical course of COVID-19 has also not been explored. OBJECTIVES: The main objectives were to determine the frequency of GI and hepatic manifestations of COVID-19 and to explore their relationship with severe clinical course. METHODS: We searched PubMed for studies published between January 1, 2020, and March 25, 2020, with data on GI and hepatic manifestations in adult patients with COVID-19. These data were compared between patients with severe and good clinical course using the random-effects model and odds ratio (OR) as the effect size. If the heterogeneity among studies was high, sensitivity analysis was performed for each outcome. RESULTS: We included 62 studies (8301 patients) in the systematic review and 26 studies (4676 patients) in the meta-analysis. Diarrhea was the most common GI symptom (9%), followed by nausea/vomiting (5%) and abdominal pain (4%). Transaminases were abnormal in approximately 25%, bilirubin in 9%, prothrombin time (PT) in 7%, and low albumin in 60%. Up to 20% patients developed severe clinical course, and GI and hepatic factors associated with severe clinical course were as follows: diarrhea (OR 2), high aspartate aminotransferase (OR 1.4), high alanine aminotransferase (OR 1.6), high bilirubin (OR 2.4), low albumin (OR 3.4), and high PT (OR 3). CONCLUSIONS: GI and hepatic involvement should be sought in patients with COVID-19 since it portends severe clinical course. The pathogenesis of GI and hepatic involvement needs to be explored in future studies.

The mechanism and treatment of gastrointestinal symptoms in patients with COVID-19.

In addition to the typical respiratory response, new coronavirus disease 2019 (COVID-19) is also associated with very common gastrointestinal symptoms. Cases with gastrointestinal symptoms are more likely to be complicated by liver injury and acute respiratory distress syndrome (ARDS). If not treated in time, coma and circulatory failure may ensue. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the human body through the combination of angiotensin-converting enzyme 2 (ACE2) in the gastrointestinal tract, the mechanism underlying the gastrointestinal symptoms may involve damage to the intestinal mucosal barrier and promotion of the production of inflammatory factors. Indeed, after cells in the lungs become infected by SARS-CoV-2, effector CD4+ T cells reach the small intestine through the gut-lung axis, causing intestinal immune damage and diarrhea; early extensive use of antibacterial and antiviral drugs can also lead to diarrhea in patients. Thus, treatment options for COVID-19 patients should be promptly adjusted when they have gastrointestinal symptoms. As SARS-CoV-2 has been detected in the feces of COVID-19 patients, future prevention and control efforts must consider the possibility of fecal-oral transmission of the virus.

Intra-abdominal hypertension as a trigger of "gut failure" in SARS-CoV-2 infection: Effect of open abdomen (OA) and negative pressure therapy (NPT) on respiratory and gastrointestinal (GI) function.

COVID-19 gastrointestinal manifestations could be attributed to SARS-CoV-2-induced small vessel thrombosis. OA with NPT treatment may have a role in optimization of bowel microcirculation and in the reduction of the endothelial and the systemic cytokine-related damage, improving also respiratory function.

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.