Gastroenterology and Hepatology from Bed to Bench

¹Dentistry Clinical Research Development Center, Birjand University of Medical Sciences, Birjand, Iran

²Infection disease Research center, Birjand University of Medical Sciences, Birjand, Iran

(Please cite as: Osmani F. Problems with the accurate reporting of COVID-19 statistics in Iran. Gastroenterol Hepatol Bed Bench 2020;13(4):275-77).

Mohamad Amin Pourhoseingholi¹, Sajad Shojaee², Sara Ashtari¹

¹Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

²Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

 (Please cite as: Pourhoseingholi MA, Shojaee S, Ashtari S. Three potential challenges in studying COVID-19 pandemic data: Chinese statistics, social media, and preprint servers. Gastroenterol Hepatol Bed Bench 2020;13(4):278-79).

Char Leung, Alice PY Wong

Deakin University  

 (Please cite as: Leung CH, Wong APY. The role of angiotensin-converting enzyme 2 (ACE2) receptor in the intestine in COVID-19: more research needed. Gastroenterol Hepatol Bed Bench 2020;13(4):280-281).

Aim: This study aimed to determine whether patients with elevated CRP, TNFα, and IL-6 levels may be at increased risk for severe infection and liver damage of COVID-19.

Background: The COVID-19 outbreak is a serious health problem to human beings. The evidence suggests that inflammatory markers related to liver damage increase in severe forms of COVID-19 compared to mild cases.

Methods: The electronic databases ISI Web of Science, EMBASE, and Cochrane Library were comprehensively searched for articles published up to May, 2020. Data from each identified study was combined using the random effects model to estimate standardized mean difference (SMD) and 95% confidence intervals (95% CIs). Sensitivity and publication bias were also calculated.

Results: Totally, 23 studies were included in this meta-analysis comprising 4313 patients with COVID-19. The random effects results demonstrated that patients with severe COVID-19 had significantly higher levels of CRP [SMD = 3.26 mg/L; (95% CI 2.5, 3.9); p<0.05; I2 = 98.02%; PHeterogeneity = 0.00], TNFα [SMD = 1.78 ng/mL; (95% CI 0.39, 3.1); p=0.012; I2 = 98.2%; PHeterogeneity = 0.00], and IL-6 [ SMD = 3.67 ng/mL; (95% CI 2.4, 4.8); p<0.05; I2 = 97.8%; PHeterogeneity = 0.00] compared with those with the mild form of the disease. Significant heterogeneity was present. No significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity.

Conclusion: The data suggests that enhanced inflammation may be associated with COVID-19-related liver damage, possibly involving inflammatory marker-related mechanisms.

Keywords: COVID-19, Coronavirus, Inflammatory markers, CRP, TNFα, IL-6, Meta-analysis.

(Please cite as: Amiri-Dashatan N, Koushki M, Ghorbani F, Naderi N. Increased inflammatory markers correlate with liver damage and predict severe COVID-19: a systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench 2020;13(4):282-291).

Aim: The current study aimed to report a pooled analysis of the association of the circulating levels of liver enzymes and total bilirubin with severe and non-severe COVID-19.

Background: The ongoing coronavirus outbreak is an important threat to health worldwide. Epidemiological data representing greater risk of liver failure in patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Methods: Electronic databases were comprehensively searched using Medline, ISI Web of Science, EMBASE, and the Cochrane Library up to July 2020. Outcomes from each relevant study were pooled using a random-effects model. Heterogeneity was analyzed by Q test and I² statistics. Sensitivity analysis was also evaluated.

Results: A total of 24 studies were included (4,246 patients) in this study. We found a significant association of COVID-19 severity with increased levels of ALT [SMD: 1.40 U/L; 95% CI (0.93, 1.88); P < 0.05, I² = 96.5%, P_{Heterogenity =} 0.000 ], AST [SMD: 2.11 U/L; 95% CI (1.40, 2.83); P < 0.05, I² = 97.9%, P_{Heterogenity =} 0.000], LDH [SMD: 3.88 U/L; 95% CI (2.70, 5); P < 0.05, I² = 98.7%, P_{Heterogenity =} 0.000] and TBil [SMD: 1.08 mmol/L; 95% CI (0.44, 1.72); P = 0.001, I² = 97.7, P_{Heterogenity =} 0.000], whereas, ALP values [SMD: 0.31; 95% CI (-1.57, 2.20); P = 0.74] was not significant between severe and non-severe COVID-19 patients. Moreover, elevated liver enzymes were found more in males [OR: 1.52, (95% CI 1.26, 1.83), P < 0.05] with severe COVID-19 infection than in females.  

Conclusion: The alterations of liver function indexes caused by SARS-CoV-2 infection suggested a potential prognosis biomarker for screening of severe patients at early stages of the disease.

Keywords: COVID-19, Coronavirus, Liver damage, Liver enzymes, Meta-analysis.

(Please cite as: Shokri Afra H, Amiri-Dashatan N, Ghorbani F, Maleki I, Rezaei-Tavirani M. Positive association between severity of COVID-19 infection and liver damage: a systematic review and meta-analysi. Gastroenterol Hepatol Bed Bench 2020;13(4):292-304).

Aim: This review study was conducted to evaluate the symptoms of COVID-19 in pregnant women with a focus on gastrointestinal symptoms.

Background: COVID-19 is a fatal respiratory disease caused by a novel coronavirus that quickly became a pandemic. Although the main symptoms of this disease include respiratory symptoms, gastrointestinal manifestations have also been observed in some patients suffering from COVID-19. Pregnant women are among the most vulnerable groups in the community to infectious diseases.

Methods: Scientific databases were searched for articles published up to May 8, 2020. Any type of study investigating the manifestations of COVID-19 in pregnant women was included. Symptoms of the disease in pregnant women with an emphasis on gastrointestinal symptoms were assessed.

Results: The search resulted in 852 titles and abstracts, which were narrowed down to 43 studies involving 374 women. The most common symptoms of patients were fever (59.1%) and cough (48.4%), respectively. Gastrointestinal symptoms included diarrhea (4.5%), abdominal pain (1.6%), nausea (0.8%), and loss of appetite (0.3%), respectively. In studies on pregnant women with gastrointestinal symptoms, 13 fetal abortions occurred, most of which were induced abortions due to the risks posed by COVID-19.In thirty cases, and infected pregnant women reported a history of chronic pregnancy-related diseases.

Conclusion: COVID-19 in pregnant women, similar to the general population, can present with gastrointestinal manifestations. The gastrointestinal tract can be a potential route for infection with the novel coronavirus.

Keywords: COVID-19, Novel Coronavirus Infection, Pregnancy, Diarrhea, Gastrointestinal Tract.

(Please cite as: Makvandi S, Ashtari S, Vahedian-Azimi A. Manifestations of COVID-19 in pregnant women with focus on gastrointestinal symptoms: a systematic review. Gastroenterol Hepatol Bed Bench 2020;13(4):305-312).

Aim: The present study aims to evaluate the prognostic value of liver-related laboratory parameters in COVID-19.

Background: This is not the first nor will it be the last time that a member of the β-coronaviruses wages a full-scale war against human health. Notwithstanding atypical pneumonia being the primary symptom, the emergence of severe disease mainly resulting from the injury of non-pulmonary organs leaves no alternative, in some cases, other than a dreadful death.

Methods: To provide a well-conceptualized viewpoint representing the prognostic values of liver-related laboratory parameters in COVID-19, a meta-analysis was performed with the calculation of mean difference and 95% confidence intervals of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Bili), and albumin (Alb) in severe and non-severe COVID-19 patients.

Results: While severe COVID-19 cases displayed higher values of ALT, AST, and Bili compared to non-severe patients (mean differences of 7.48, 12.07, and 3.07, respectively), the value of Alb was significantly lower in severe cases (mean differences of -6.15). There was also a correlation between alterations in all of the parameters; however, only correlations between ALT and Bili (R=0.98, p=0.0031), and Bili and Alb (R=-1, p=0.0012) were significant.

Conclusion: Abnormal values of liver-related examinations outwardly contribute to reflect the progression of the disease toward an unfavorable outcome. Therefore, careful scrutiny of these parameters will provide clinicians with invaluable information regarding SARS-CoV-2 infection, at least in terms of liver injury.

Keywords: COVID-19, Prognosis, Liver; Albumin, Bilirubin, Aminotransferase.

(Please cite as: Bashash D, Olfatifar M, Hadaegh F, Asadzadeh Aghdaei H, Zali MR. COVID-19 prognosis: What we know of the significance and prognostic value of liver-related laboratory parameters in SARS-CoV-2 infection. Gastroenterol Hepatol Bed Bench 2020;13(4):313-320).

Aim: The current research aimed to analyze and summarize observational studies that compared the incidence of gastrointestinal symptoms in mild and severe COVID-19 infection.

Background: Coronavirus disease 2019 (COVID-19) has been identified as a public health threat worldwide. Previous studies, however, have reported contradictory results of COVID-19-related gastrointestinal symptoms in severe and mild forms.

Methods: A search of Medline, ISI Web of Science, EMBASE, and Cochrane Library databases was conducted for articles published up to May 2020. Data from each study was combined using the random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Sensitivity was examined by sequentially excluding one study in each turn. Publication bias was evaluated using the Egger’s and Begg’s tests.

Results: Twenty studies (4,265 patients) were reviewed. It was found that the prevalence of diarrhea [OR (0.40), (95% CI 0.91, -2.16), p = 0.03, I2 = 88.1%, PHeterogenity = 0.00)] and nausea and vomiting [OR (0.27), (95% CI 0.07, 1.01), p = 0.05, I2 = 89.3%, PHeterogenity = 0.00)] increased significantly in the severe form compared to the mild form of COVID-19, while abdominal pain and anorexia had no significant increased prevalence in admitted and hospitalized COVID-19 patients. Moreover, COVID-19-related gastrointestinal symptoms were seen in higher rates in males [OR (1.42), (95% CI 1.23, 1.65), p < 0.05, I2= 18.4%, PHeterogenity = 0.23] than in females. No significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity.

Conclusion: The data provides valuable information for the discovery of prognosis biomarkers to diagnosis more severe disease in the early stages of COVID-19.

Keywords: COVID-19, Coronavirus, Gastrointestinal symptoms, Digestive symptoms, Meta-analysis.

(Please cite as: Arjmand B, Ghorbani F, Koushki M, Rezai-Tavirani M. Gastrointestinal symptoms in patients with mild and severe COVID-19: a scoping review and meta-analysis. Gastroenterol Hepatol Bed Bench 2020;13(4):321-330).

The current review aimed to synthesize the literature on the complex relationship between food consumption and nutritional status as well as the digestive system in order to examine the relationship between immunity and potential responses to COVID-19 infection. The goal is to help inform the many healthcare professionals working with COVID-19 patients. A literature search was performed on PubMed, Scopus, and EMBASE databases. Hand searches were also undertaken using Google and reference lists to identify recent evidence. Studies were critically appraised, and the findings were analyzed by narrative synthesis. Nutritional status can impact immunity in several ways, including affecting susceptibility to infection, severity of disease, and recovery time, and is therefore a significant consideration in the management of COVID-19. COVID-19 can also impact digestive function, which can further impact nutritional status. The role of Vitamin D deficiency in vulnerability to severe respiratory infections, including COVID-19, has been recognized, and it may have a role in treatment where deficiency is indicated. Healthcare professionals should be aware that obesity may be accompanied by micronutrient malnutrition including vitamin D deficiency and alterations in the microbiome and inflammatory responses, which can further impact immunity and disease severity. Multidisciplinary team-work is recommended in the management of patients with COVID-19, and approaches should include a consideration of nutritional status (both macronutrients and micronutrients), body weight, and gastrointestinal signs and symptom.

Keywords: obesity, COVID-19, nutritional status, vitamin D, microbiome, multidisciplinary, supplementation, practice.

(Please cite as: Bold J, Harris M, Fellows L, Chouchane M. Nutrition, the digestive system and immunity in COVID-19 infection. Gastroenterol Hepatol Bed Bench 2020;13(4):331-340).

The coronavirus disease (Covid-19) has caused a pandemic with more than 600,000 deaths to date. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the beta-coronavirus genus that also includes SARS and the Middle East Respiratory Syndrome Coronavirus (MERS). While the typical presentation is given by respiratory symptoms and fever, some patients also report gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Several studies have identified the SARS-CoV-2 RNA in stool specimens of infected patients, and its viral receptor angiotensin-converting enzyme 2 (ACE2) is highly expressed in enterocytes. In this short review, we report the frequency of gastrointestinal symptoms in infected patients and suggest possible implications for disease management, transmission, and infection control.

Keywords: Angiotensin-converting enzyme 2, COVID-19, Diarrhea, Gastrointestinal Presentation, Nausea, SARS-CoV-2, Vomiting.

(Please cite as: Caio G, Lungaro L, Cultrera R, De Giorgio R, Volta U. Coronaviruses and gastrointestinal symptoms: an old liaison for the new SARS-CoV-2. Gastroenterol Hepatol Bed Bench 2020;13(4):341-350).

The coronavirus disease 2019 (COVID-19) is responsible for the new pandemic, which remains an important health and economic challenge worldwide. The causative agent is a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is similar to SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Adult infection with respiratory symptoms was considered in the beginning of the pandemic. Now, it has been reported that SARS-CoV-2 infects children and other organs such as the gastrointestinal tract. SARS-CoV-2 enters the host cells through angiotensin converting enzyme-2 (ACE2) receptors as the main receptor expressed in various organs such as the lungs and gastrointestinal tract. Studies on children and the clinical manifestations of COVID-19 do not completely explain the natural course of infection in children, and precisely how the GI tract is involved is not understood. The present article highlights the gastrointestinal manifestations and pathological findings in children with COVID-19. According to the evidence, SARS-CoV-2 infection is milder in children and may present different clinical symptoms from adults. Common clinical manifestations of pediatric COVID-19 include cough, fever, sore throat, malaise, fatigue, and GI symptoms such as diarrhea, abdominal pain, nausea, and vomiting. Furthermore, liver and pancreatic enzymes may be elevated during the pediatric COVID-19 course. Asymptomatic children carriers are potential sources of infection for adults, especially elderly ones. Diagnosis, treatment, and isolation of children are the most effective ways to control the expansion of the COVID-19 pandemic.

Keywords: SARS-CoV-2, Pediatric COVID-19, Gastroenterology.

(Please cite as: Rohani P, Ahmadi Badi S, Moshiri A, Siadat SD. Coronavirus disease 2019 (COVID-19) and pediatric gastroenterology. Gastroenterol Hepatol Bed Bench 2020;13(4):351-354).

Aim: This study demonstrated potent inhibitors against COVID-19 using the molecular docking approach of FDA approved viral antiprotease drugs.

Background: COVID-19 has now spread throughout world. There is a serious need to find potential therapeutic agents. The 3C-like protease (Mpro/6LU7) is an attractive molecular target for rational anti-CoV drugs

Methods: The tertiary structure of COVID-19 Mpro was obtained from a protein data bank repository, and molecular docking screening was performed by Molegro Virtual Docker, ver. 6, with a grid resolution of 0.30 Å. Docking scores (DOS) are representative of calculated ligand-receptor (protein) interaction energy; therefore, more negative scores mean better binding tendency. Another docking study was then applied on each of the selected drugs with the best ligands separately and using a more accurate RMSD algorithm.

Results The docking of COVID-19 major protease (6LU7) with 17 selected drugs resulted in four FDA approved viral antiprotease drugs (Temoporfin, Simeprevir, Cobicistat, Ritonavir) showing the best docking scores. Among these 4 compounds, Temoporfin exhibited the best DOS (-202.88) and the best screened ligand with COVID-19 Mpro, followed by Simeprevir (-201.66), Cobicistat (-187.75), and Ritonavir (-186.66). As the best screened ligand, Temoporfin could target the Mpro with 20 different conformations, while Simeprevir, Cobicistat, and Ritonavir make 14, 10, and 10 potential conformations at the binding site, respectively.

Conclusion: The findings showed that the four selected FDA approved drugs can be potent inhibitors against COVID-19; among them, Temoporfin may be more potent for the treatment of the disease. Based on the findings, it is recommended that in-vitro and in-vivo evaluations be conducted to determine the effectiveness of these drugs against COVID-19.

Keywords: COVID-19, Main protease, Mpro/6LU7, Molecular docking, Viral antiprotease drugs.

(Please cite as: Absalan AR, Doroud D, Salehi-Vaziri M, Kaghazian H, Ahmadi N, Zali F, et al. Computation screening and molecular docking of FDA approved viral protease inhibitors as a potential drug against COVID-19. Gastroenterol Hepatol Bed Bench 2020;13(4):355-360).

Aim: This research aimed to investigate neutrophil‐to‐lymphocyte ratio (NLR) with C‐reactive protein to identify potential clinical predictors and analyze differences among severe and non-severe COVID-19 patients.

Background: NLR and CRP are established markers that reflect systemic inflammatory, and these parameters alter in patients with novel coronavirus (SARS-CoV-2) pneumonia (COVID-19).

Methods: A population of patients with COVID-19 referred to Loghman Hospital in Tehran was analyzed. The baseline data of laboratory examinations, including NLR and CRP levels, was collected. Pearson analysis was used to assess the independent relationship between the NLR with disease severity and CRP levels.

Results: COVID-19 cases comprised 14 (20%) patients with severe disease and 56 (80%) with non-severe infection. The mean values of WBC, NEU, LYM, and NLR of the severe patients were significantly higher than those of the non-severe patients. Forty-six patients (65.7%) had NLR >1, and the remaining patients had NLR <1. Plasma CRP levels were higher in severe cases than in non-severe cases, and this difference was significant. The results showed that NLR was positively correlated with CRP levels (R=0.23) and negatively correlated with WBC (R=-0.38). CRP (AUC = 0.97, 95% CI: 0.95-0.99) and NLR (AUC = 0.87, 95% CI: 0.81-0.93) had very good accuracy in predicting the severity of COVID-19 disease.

Conclusion: The findings of this study indicated that the integration of NLR and CRP may lead to improved predictions and is recommended as a valuable early marker to assess prognosis and evaluate the severity of clinical symptoms in COVID-19 patients.

Keywords: SARS-CoV-2, neutrophil‐to‐lymphocyte ratio (NLR), CRP, COVID-19.

(Please cite as: Mousavi-Nasab SD, Mardani R, Nasr Azadani H, zali F, Ahmadi Vasmehjani A, Sabeti SH, et al. Neutrophil to lymphocyte ratio and C-reactive protein level as prognostic markers in mild versus severe COVID-19 patients. Gastroenterol Hepatol Bed Bench 2020;13(4):361-366).

Aim: Introducing possible diagnostic and therapeutic biomarker candidates via the identification of chief dysregulated proteins in COVID-19 patients is the aim of this study.

Background: Molecular studies, especially proteomics, can be considered as suitable approaches for discovering the hidden aspect of the disease.

Methods: Differentially expressed proteins (DEPs) of three patients with demonstrated severe condition (S-COVID-19) were compared to healthy cases by a proteomics study. Cytoscape software and STRING database were used to construct the protein-protein interaction (PPI) network. The central DEPs were identified through topological analysis of the network. ClueGO+CluePedia were applied to find the biological processes related to the central nodes. MCODE molecular complex detection (MCODE) was used to discover protein complexes.

Results: A total of 242 DEPs from among 256 query ones were included in the network. Centrality analysis of the network assigned 16 hub-bottlenecks, nine of which were presented in the highest-scored protein complex. Ten protein complexes were determined. APOA1 was identified as the protein complex seed, and APP, EGF, and C3 were the top hub-bottlenecks of the network. The results specify that up-regulation of C3 and down-regulation of APOA1 in urine play a role in the stiffness in respiration and, accordingly, the severity of COVID-19. Moreover, dysregulation of APP and APOA1 could both contribute to the possible adverse effects of COVID-19 on the nervous system.

Conclusion: The introduced central proteins of the S-COVID-19 interaction network, particularly APOA1, can be considered as diagnostic and therapeutic targets related to the coronavirus disease after being approved with complementary studies.

Keywords: urine proteome, COVID-19, protein interaction mapping, biomarkers, biological process.

(Please cite as:Zamanian Azodi M, Arjmand B, Zali AR,  Rezaei Tavirani M, Razzaghi MR. Introducing APOA1 as a key protein in COVID-19 infection: a bioinformatics approach. Gastroenterol Hepatol Bed Bench 2020;13(4):367-373).

Aim: The present study aimed to identify human protein–host protein interactions of SARS-CoV-2 infection in the small intestine to discern the potential mechanisms and gain insights into the associated biomarkers and treatment strategies.

Background: Deciphering the tissue and organ interactions of the SARS-CoV-2 infection can be important to discern the potential underlying mechanisms.  In the present study, we investigated the human protein–host protein interactions in the small intestine.

Methods: Public databases and published works were used to collect data related to small intestine tissue and SARS-CoV-2 infection. We constructed a human protein-protein interaction (PPI) network and showed interactions of host proteins in the small intestine. Associated modules, biological processes, functional pathways, regulatory transcription factors, disease ontology categories, and possible drug candidates for therapeutic targets were identified.

Results: Thirteen primary protein neighbors were found for the SARS-CoV-2 receptor ACE2. ACE2 and its four partners were observed in a highly clustered module; moreover, 8 host proteins belonged to this module. The protein digestion and absorption as a significant pathway was highlighted with enriched genes of ACE2, MEP1A, MEP1B, DPP4, and XPNPEP2. The HNF4A, HNF1A, and HNF1B transcription factors were found to be regulating the expression of ACE2. A significant association with 12 diseases was deciphered and 116 drug-target interactions were identified.

Conclusion: The protein-host protein interactome revealed the important elements and interactions for SARS-CoV-2 infection in the small intestine, which can be useful in clarifying the mechanisms of gastrointestinal symptoms and inflammation. The results suggest that antiviral targeting of these interactions may improve the condition of COVID-19 patients.

Keywords: SARS-CoV-2, small intestine, interactome, protein interaction network, regulatory network, drug targets.

(Please cite as: Khodadoost M, Niknam Z, Farahani M, Razzaghi MR, Norouzinia M. Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine. Gastroenterol Hepatol Bed Bench 2020;13(4):374-387).

Aim: Evaluating the expression level of CD4⁺ FoxP3⁺ CD25⁺ T cells and IL-6 in peripheral blood samples of hospitalized COVID-19 patients.

Background: COVID-19 is an emerging disease with worldwide distribution. However, there is a little data about the correlation between the disease and the host immune responses.

Methods: Whole blood samples of 30 COVID-19 patients and eight healthy people were collected during March to June 2020. Total RNA was extracted from the samples, cDNA synthesis was performed, and the expression level of targeted genes was evaluated using quantitative real-time PCR.

Results: The expression level of CD4, CD25, and Foxp3 was significantly downregulated 5-, 2-, and 3-fold, respectively, among COVID-19 patients in comparison to healthy controls (P-value < 0.0001). The expression level of IL-6 represented almost 18-fold increase in COVID-19 patients compared to healthy controls.

Conclusion: Our findings indicated the expression profile analysis of CD4⁺ FoxP3⁺ CD25⁺ T cells could be a potential marker for the assessment of severity of COVID-19 patients.

Keywords: COVID-19, SARS-CoV-2, Inflammatory responses, Treg, Interleukin 6.

(Please cite as: Mohebbi SR, Baghaei K, Rostami-Nejad M, Nazemalhosseini Mojarad E, Mirjalali H, Yadegar A, et al. Significant changes of CD4, FOXP3, CD25, and IL6 expression level in Iranian COVID-19 patients. Gastroenterol Hepatol Bed Bench 2020;13(4):388-392).

Diarrhea is common after liver transplant. Although the majority of the episodes are experienced during the first year of transplantation, but some of them can be seen at any time after the procedure. Diarrhea can impose a major risk of morbidity and mortality on transplanted patients; so a careful evaluation is required to manage it. There are few studies highlighting the gastrointestinal manifestations of COVID-19, in particular among immunosuppressed patients. Predominant respiratory symptoms of coronavirus is the reason why GI aspects of the virus are usually overlooked. This study represents a young woman with a history of liver transplant who was referred to the hospital because of diarrhea, fever and abdominal pain attributed to coronavirus infection.

Today, COVID-19 pneumonia causes global concern. The World Health Organization (WHO) has reported many mortalities from this disease all around the world. Therefore, recognizing new cases of COVID-19 is crucial during this pandemic. Many studies have shown that COVID-19 has a broad spectrum of signs and symptoms, including GI and cutaneous manifestations. Previous studies have reported liver enzyme changes as well as diarrhea as a common GI manifestation of COVID-19. However, there are few reports about COVID-19 synchronous cutaneous and liver involvement. Additionally, there are few reports about intrahepatic cholestasis in COVID-19 patients. In this article, a confirmed case of COVID-19 with vasculopathy-related cutaneous manifestation and liver cholestasis is reported. A 67-year-old Iranian woman was admitted to Taleghani Hospital with epigastric pain, vomiting, anosmia, rising liver enzyme levels, fever, itching, and skin rashes. Skin and liver biopsies were performed during the patient’s admission; the results suggested vasculopathy-related cutaneous lesion and liver cholestasis. Plasmapheresis was initiated and all manifestations disappeared after treatment. All atypical presentations, including cutaneous lesions and liver manifestations, should be considered as COVID-19 and evaluated.

Keywords: COVID-19, cholestasis, liver, vasculitis, cutaneous lesion, skin

(Please cite as: Sadeghi A, Dooghaie Moghadam A, Eslami P, Pirsalehi A, Salari S , Roshandel E. Vasculopathy-related Cutaneous Lesions and Intrahepatic Cholestasis as Synchronous Manifestations in a COVID-19 Patient: a Case Report. Gastroenterol Hepatol Bed Bench 2020;13(4):400-404).

 COVID-19 is a new contagious viral pneumonia with various signs and symptoms, including loss of consciousness, liver injury, and cerebrovascular accident; however, there is little data on the manifestation and outcome of COVID-19 in liver transplant patients. Moreover, because transplant units in Iran were closed from the first day of the COVID-19 pandemic, accurate data about nosocomial COVID-19 and the liver transplant setting is not available. In this article, we introduce a liver transplant recipient with a final fatal outcome, who had had neurological manifestations, and whose COVID-19 manifestations began in the hospital within 2 days of transplant surgery.

Keywords: covid-19, liver, transplantation, liver transplantation, Neurological complications.

(Please cite as: Eslami P, Moradi MH, Dooghaie Moghadam A, Pirsalehi A, Abdul Lateef Sh, Hadaegh AR, et al. Lethal outcome of Covid-19 pneumonia in a new liver recipient with neurological manifestation. Gastroenterol Hepatol Bed Bench 2020;13(4):405-409).

As of December 2019, a new strain of coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was discovered in Wuhan, China, following an epidemic of a fast-spreading viral respiratory disease, later called Coronavirus Disease 2019 (COVID-19), which then lead to the present pandemic the world has come to know. Patients who tested positive for COVID-19 are mostly asymptomatic or present with mild self-limiting symptoms. While GI symptoms occur with less prevalence, they are increasingly being reported. A diagnosis of Covid-19 has increased dramatically in patients presenting with gastrointestinal symptoms suggesting that GI symptoms should be taken into serious consideration with patient diagnosis.

Case 1: A 65-year-old man presented to the hospital emergency room with abdominal pain, Murphy's sign and chills without fever, subsequently diagnosed as acute acalculous cholecystitis with a positive COVID-19 rRT-PCR.

Case 2: A 78-year-old woman presented to the hospital emergency room complaining of severe positional epigastric pain precipitated by lying supine, chills with no fever, being later diagnosed as acute pancreatitis and a positive COVID-19 rRT-PCR. It has become evident that the ACE2 receptor plays a significant role as the entry site into human cells for the virus. This receptor is generally expressed in respiratory cells, as well as the gastrointestinal tract, corresponding with extrapulmonary manifestations of COVID-19. Studies concluded that the origin of gastrointestinal symptoms could be caused by the interaction of the SARS-CoV-2 virus with cells through the ACE2 receptor.  The findings of the present study support this theory, as both patients presented with symptoms regarding tissues with high ACE2 expression.

Keywords: Case Reports, Gastrointestinal Manifestations, COVID-19.

(Please cite as: Hassani AH, Beheshti A, Almasi F, ketabi Moghaddam P, Azizi MR, Shahrokh SH. Unusual gastrointestinal manifestations of COVID-19: two case reports Gastroenterol Hepatol Bed Bench 2020;13(4):410-414).

¹Clinical Investigation Laboratory, Ospedale Maggiore di Crema, Crema, Italy

²Clinical Investigation Laboratory, Ospedale Bolognini Seriate, Bergamo, Italy

(Please cite as: Assandri R, Montanelli A. Covid-19 Gastrointestinal symptoms are not a secondary clinical manifestation: the Italian experience. Gastroenterol Hepatol Bed Bench 2020;13(4):415-416).

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

(Please cite as: Abbasinazari M. Possible role of zinc (Zn) as an adjunctive therapy in gastrointestinal symptoms of COVID-19 infectious disease. Gastroenterol Hepatol Bed Bench 2020;13(4):417-418).

¹Eye Research Center, The five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

²Department of Biostatistics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

 (Please cite as: Chaibakhsh S, Vahedi M. Comment on “Predicting the mortality due to Covid-19 by the next month for Italy, Iran and South Korea; a simulation study”. Gastroenterol Hepatol Bed Bench 2020;13(4):419-420).

¹Student’s Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

²Hearing Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

(Please cite as: Mirmomeni G, Bayat A. Predicting the mortality due to covid-19 by the next month for Italy, Iran and South Korea; a simulation study. Gastroenterol Hepatol Bed Bench 2020;13(4):421).

Diarrhea is common after liver transplant. Although the majority of episodes are experienced during the first year of transplantation, they can occur any time after the procedure. Diarrhea can impose a major risk of morbidity and mortality on transplanted patients; so a careful evaluation is required to manage it. There are few studies highlighting the gastrointestinal manifestations of COVID-19, in particular among immunosuppressed patients. The predominant respiratory symptoms of coronavirus cause GI aspects of the virus to be overlooked. This study represents a young woman with a history of liver transplant who was referred to the hospital because of diarrhea, fever, and abdominal pain attributed to coronavirus infection.

Keywords: COVID-19, liver transplant, Diarrhea.

(Please cite as: Hatami B, Ketabi Moghadam P, Zali MR. Presentation of COVID-19 in a liver transplant recipient. Gastroenterol Hepatol Bed Bench 2020;13(4):396-399).