ISSN: 2008-2258


Systematic Review and Meta-analysis

Increased inflammatory markers correlate with liver damage and predict severe COVID-19: a systematic review and meta-analysis

Nasrin Amiri-Dashatan, Mehdi Koushki, Fatemeh Ghorbani, Nosratollah Naderi

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

Aim: We aim here to seek whether or not patients with elevated CRP, TNF-a and IL-6 levels may be at increased chance of the severe type and liver damage of COVID-19.

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

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

Results: Totally 23 studies were included in this meta-analysis comprising of 4313 patients
with COVID-19. Random-effects results demonstrated that patients with COVID-19 in
severe group had significantly higher levels of CRP [SMD = 3.26 mg/L; (95% CI 2.5, 3.9); P<0.05; I2 = 98.02%; P Heterogeneity = 0.00], TNF-a [SMD = 1.78 ng/mL; (95% CI 0.39, 3.1); P=0.012; I2 = 98.2%; P Heterogeneity = 0.00] and IL-6 [ SMD = 3.67 ng/mL; (95% CI 2.4, 4.8); P<0.05; I2 = 97.8%; P Heterogeneity = 0.00] compared to with those in mild group. 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: These data suggest that enhanced inflammation may be associated with COVID-19-related liver damage, possibly involving inflammatory markers related mechanisms.

Positive association between severity of COVID-19 infection and liver injury: a systematic review and meta-Analysis

Hajar Shokri Afra, Nasrin Amiri-Dashatan, Fatemeh Ghorbani, Iradj Maleki, Mostafa Rezaei –Tavirani

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

Aim: 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 novel 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 Cochrane Library up to July 2020. Outcomes from each relevant study were pooled using random-effects model. Heterogeneity was analysed by Q test and I2 statistics. Sensitivity analysis was also evaluated.

Results: A total of 24 studies were included (4,246 patients). 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%, PHeterogenity= 0.000 ], AST [SMD: 2.11 U/L; 95% CI (1.40, 2.83); P<0.05, I2 = 97.9%, PHeterogenity= 0.000], LDH [SMD: 3.88 U/L; 95% CI (2.70, 5); P<0.05, I2 = 98.7%, PHeterogenity= 0.000] and TBil [SMD: 1.08 mmol/L ; 95% CI (0.44, 1.72); P = 0.001, I2=97.7, PHeterogenity= 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 in males [OR: 1.52, (95% CI 1.26, 1.83), P<0.05] with severe COVID-19 infection than females.

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

The manifestations of COVID-19 in pregnant women with focus on gastrointestinal symptoms; a systematic review

Somayeh Makvandi, Sara Ashtari, Amir Vahedian-azimi

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

Introduction: COVID-19 is a fatal respiratory disease caused by a novel coronaviruses that quickly became a pandemic. Although the main symptoms of this disease include respiratory symptoms, the gastrointestinal manifestations have also been observed in some patients who suffered from COVID-19. Pregnant women are among the most vulnerable groups in the community to infectious diseases. This review study was conducted to evaluate the symptoms of COVID-19 in pregnant women with a focus on gastrointestinal symptoms.

Methods: We searched the scientific databases from their inception to May8, 2020. Any type of studies investigating the manifestations of COVID-19in pregnant women was included in the study. Symptoms of the disease in pregnant women were assessed with emphasis on gastrointestinal symptoms

Results: The search resulted in 852 titles and abstracts, which were narrowed down to 43 studiesinvolving 374 women. The most common symptoms of patients were fever (59.1%) and caught (48.4%), respectively. Gastrointestinal symptoms include diarrhea (4.5%), abdominal pain (1.6%), nausea (0.8%), and loss of appetite (0.3%), respectively. In studies of 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, infected pregnant women reported a history of the chronicpregnancy-related diseases.

Conclusion: COVID-19 in pregnant women, similar tothe general population, can present with gastrointestinal manifestations. The gastrointestinal tract can be a potential route for infection with the novel coronavirus. In pregnant women, regular screening is recommended for gastrointestinal symptoms of COVID-19 as well as respiratory symptoms.

COVID-19 prognosis: what we know of the significance and prognostic value of liver-related laboratory parameters in SARS-CoV-2 infection?

Davood Bashash, Meysam Olfatifar , Farzad Hadaegh , Hamid Asadzadeh Aghdaei, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

This is not the first nor it will be the last time that a member of ?-coronaviruses is waging a full-scale war against human health. Notwithstanding atypical pneumonia being the primary symptom, emergence of severe disease mainly resulting from the injury of non-pulmonary organs leaves no choice, in some cases, rather than a dreadful death. To provide a well-conceptualized viewpoint representing prognostic values of liver-related laboratory parameters in COVID-19, we planned to perform a meta-analysis of pertinent literature. While severe COVID-19 cases displayed higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (Bili) compared to non-severe patients (mean differences of 7.48, 12.07, 3.07), value of albumin (Alb) was significantly lower in severe cases (mean differences of -6.15). There was also correlation between alterations of all these 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. In conclusion, the present study highlighted that abnormal values of liver-related examinations outwardly contribute to reflect progression of the disease toward an unfavorable outcome and therefore, careful scrutiny of these parameters will provide clinicians with invaluable information in SARS-CoV-2 infection, at least in term of liver injury. Even though, at the time of writing this article, the lack of adequate and appropriate studies is the most challenging issue facing us, planning of future research aiming to provide new clues and data will definitively cast a flash of light on the significance of these parameters.

Gastrointestinal symptoms in patients with mild and severe COVID-19: a scoping review and meta-analysis

Babak Arjmand, Fatemeh Ghorbani, Mehdi Koushki, Mostafa Rezaei –Tavirani

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

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 public health throat worldwide. However, previous studies have reported contradictory results of COVID-19-related gastrointestinal symptoms in severe and mild forms.

Methods: Databases were searched using Medline, ISI Web of Science, EMBASE, and Cochrane Library up to May 2020. Data from each study were combined using the random-effects model, to calculate Odds Ratio (ORs) and 95% confidence intervals (95% CIs). Sensitivity analysis was examined by sequentially excluding one study in each turn. Publication bias was evaluated using the Egger’s and Begg’s tests. 

Results: Totally 20 studies were included (4,265 patients). We 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 & vomiting [OR (0.27), (95% CI 0.07, 1.01), P= 0.05, I2 = 89.3%, PHeterogenity= 0.00)] significantly increased in severe COVID-19 compared to mild form, while, abdominal pain and anorexia had no significant increased prevalence in admitted and hospitalized patients with COVID-19. Moreover, COVID-19-related gastrointestinal symptoms were higher in males [OR (1.42), (95% CI 1.23, 1.65), P<0.05, I2= 18.4%, PHeterogenity= 0.23] than females. No significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity.

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

Review Article

Nutrition, the digestive system and immunity in COVID-19 infection

Justine Sara Bold, Miranda Harris, Lindsey Fellows, Manal Chouchane

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

The aim of this review is to synthesise literature on the complex relationship between food consumption and nutritional status, including the digestive system, in order to consider the relationship to immunity and potential responses to COVID-19 infection. The aim is to help to inform the many healthcare professionals working with patients with COVID-19. 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 analysed by narrative synthesis. Nutritional status can impact on 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 on digestive function which can further impact nutritional status. There is recognition of the role of Vitamin D deficiency in vulnerability to severe respiratory infections including COVID-19, 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 also alterations in the microbiome and inflammatory responses which can further impact on immunity and severity of disease. Multidisciplinary team working 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 as well as of gastrointestinal signs and symptoms.

Coronaviruses and gastrointestinal symptoms: an old liaison for the new SARS-CoV-2

Giacomo Caio, Lisa Lungaro, Rosario Cultrera, Roberto De Giorgio, Umberto Volta

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

The coronavirus disease (Covid-19) caused a pandemia with more than 600.000 deaths to date. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Beta-coronavirus genus that also includes the SARS and 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 to the disease management, transmission, and infection control.




Coronavirus disease 2019 (COVID-19) and pediatric gastroenterology

Pejman Rohani, Sara Ahmadi Badi, Arfa Moshiri, Seyed Davar Siadat

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

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

Original Article

Computation screening and Molecular Docking of FDA approved viral protease inhibitors as a potential drug against COVID-19

Abdorrahim Absalan, Delaram Doroud, Mostafa Salehi-Vaziri, Hooman Kaghazian, Nayeb Ali Ahmadi, Fatemeh Zali, Mohamamd Hassan Pouriavali's, Seyed Dawood Mousavi-Nasab

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

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

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

Methods: The tertiary structure of COVID-19 Mpro obtained from protein data bank repository and molecular docking screening was performed by Molegro Virtual Docker Ver.6 with 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. After that, we applied another docking study on each of selected drugs with best ligands separately and using a more accurate RMSD algorithm.

Result: Docking results of COVID-19 major protease (6LU7) with selected 4 FDA approved viral antiprotease drugs (Temoporfin, Simeprevir, Cobicistat, Ritonavir) out of the selected 17 showed best docking score. Out of the 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). Temoporfin as the best screened ligand 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.

Conclusions: Our findings showed that selected four FDA approved drugs can be potent inhibitors against COVID-19, however among them, the use of Temoporfin medication may be more potent for the treatment of the disease. Based on the findings, we recommend in-vitro and in-vivo evaluations to determine their effectiveness against COVID-19.

Neutrophil to lymphocyte ratio and C-reactive protein level as a prognostic marker in mild versus severe COVID-19 patients

Abbas Ahmadi Vasmehjani, Rajab Mardani, Hosein Nasr Azadani , Fatemeh Zali, Seyed Dawood Mousavi Nasab, Shahram Sabeti, Ilad Alavi Darazam, Nayeb Ali Ahmadi

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

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

Background: NLR and CRP are established inflammation markers that reflect systemic inflammatory. The patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher NLR.

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 were collected. The Pearson analysis was developed to assess the independent relationship between the NLR with disease severity and CRP levels.

Results: COVID-19 cases include 14 (20%) of patients with severity disease and 56 (80%) with non-severe COVID-19 disease.  The mean number of WBC, NEU, LYM and NLR of severe patients were significantly higher than those of non-severe patients. 46 (65.7%) of patients had NLR >1 and the remaining patients were NLR <1. The plasma CRP levels in severe cases were higher than non-severe cases that 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).The CRP (AUC = 0.97, 95% CI: 0.95-0.99), NLR (AUC = 0.87, 95% CI: 0.81-0.93), had very good accuracy in predicting disease severity of COVID-19 disease.

Conclusion: We concluded the NLR and CRP are an independent risk factor for disease severity of COVID-19 patients in respect to further researches are needed to confirm our findings.

Introducing APOA1 as a key protein in COVID-19 Infection: a bioinformatics approach

Mona Zamanian Azodi, Babak Arjmand, Alireza Zali, Mohammadreza Razzaghi

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

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

Background: The ongoing worldwide pandemic of novel coronavirus disease urges the requirements for effective clinical diagnosis and therapy approaches. Molecular studies especially proteomics can be considered as suitable methods to discover the hidden aspect of the disease.

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

Results: Numbers of 242 DEPs among 256 query ones were included in the network. Centrality analysis of the network assigned 16 hub-bottlenecks that nine were presented in the highest-scored protein complex. The number of 10 protein complexes was determined. APOA1 as the protein complex seed and, APP, EGF, and C3 are the top hub-bottlenecks of the network. The results specify that up-regulation of C3 and down-regulation of APOA1 in urine play role in stiffness in respiration and accordingly, the severity of COVID-19. Moreover, dysregulation of APP and APOA1 both could be as a part of possible adverse effects of  COVID-19 on the nervous system. A low level of urinary EGF can be considered as an indicator of a defective kidney in the presence of the virus.

Conclusion: In conclusion, the introduced central proteins particularly APOA1 can be considered as therapeutic targets and diagnostic biomarker candidates related to the coronavirus disease after complementary studies.


Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine

Mahmoud Khodadoost, Zahra Niknam , Masoumeh Farahani , Mohammadreza Razzaghi, Mohsen Norouzinia

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

Deciphering the tissue and organ interactions of the SARS-CoV-2 can be important to discern the potential underlying mechanisms and characterize drug candidates. Gastrointestinal symptoms and inflammation were frequently reported in the coronavirus disease 2019 (COVID-19). The expression pattern of ACE2 in the small intestinal as a major host receptor for SARS-CoV-2 and digestion-related enzyme has been determined. Here, we investigated interactome of the SARS-CoV-2–host protein in the small intestine tissue to detect highly clustered modules and associated mechanisms. 13 primary protein neighbors were found for ACE2 among the small intestine-specific proteins. The first module with the highest score was found as key module, since ACE2 and its four partners were observed in this module. Moreover, 8 host proteins were belonged to the highly clustered module. Functional analysis of this module highlighted protein digestion and absorption as a significant KEGG pathway with enriched genes of ACE2, MEP1A, MEP1B, DPP4, and XPNPEP2. Regulatory network revealed possible upstream regulating transcription factors that HNF factors including HNF4A, HNF1A, and HNF1B were found to be regulating the expression of ACE2 target gene. Drug-target interactions revealed associated drug classes. The SARS-CoV-2–host protein interactome revealed the important elements for virus infection in the small intestine that may help to clarify gastrointestinal symptoms and inflammation.

Significant changes of CD4, FOXP3, CD25 and IL 6 mRNA expression levels in Covid 19 patients

Seyed Reza Mohebbi, Kaveh Baghaei, Mohammad Rostami-Nejad , Ehsan Nazemalhosseini Mojarad, Hamed Mirjalali, Abbas Yadegar, Nastaran Asri, Shahrokh Abdoulahi, Hamid Assadzadeh-Aghdaei

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020


Aim: evaluation the expression level of CD4 (+) FoxP3(+) CD25(+) T cells in COVID-19 patients and assessed its correlation with the level of IL6.

Background: there is insufficient information regarding Tregs mRNA expression level and also the regulation of IL6 cascade in COVID-19 patients.

Method: Whole blood samples of 30 COVID-19 patients and also 12 healthy people were collected during 2020. Total RNA was extracted and after adjusting the RNA concentrations, cDNA synthesis was performed using cDNA synthesis kit. To evaluate the expression levels of targeted genes, q real-time PCR was performed.

Results: Based on the results, the mRNA expression levels of TCD4 (5-fold changes), CD25 and Foxp3 (2- and 3-fold, respectively) in COVID-19 patients significantly downregulated in comparison to the healthy controls (P-value<0.0001). Besides, in the line of our results, the expression levels of IL6 represented almost 20-fold increase in COVID-19 patients compared to healthy controls

Conclusion: These data proposed that Treg cells may be a biomarker of severity and remark the probability that antibodies directing IL-6 might moderating lymphocyte stability

Short Report

Case Report

Vasculopathy-related cutaneous lesions and intrahepatic cholestasis as a synchronous manifestations in COVID-19 patient: case report

Amir Sadeghi, Arash Dooghaie Moghadam, Pegah Eslami, Ali Pirsalehi, Sina Salari, Elham Roshandel

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020



Nowadays, Covid-19 pneumonia, makes many globally concerns. World health organization has reported many mortalities in all around the world, due to covid-19 disease. therefore, recognizing new cases of covid-19 is crucial during this pandemic. Many studies showed that covid-19 has broad spectrum of signs and symptoms including GI and cutaneous manifestations. Previous literatures reported liver enzyme changes and diarrhoea as a common GI manifestation of covid-19. however, there are few reports about COVID-19 cutaneous and liver synchronous involvement. Additionally, there are few reports about intrahepatic cholestasis in those patients. in this article, we attempted to introduced a COVID-19 confirmed case with vasculopathy-related cutaneous manifestation and liver cholestasis.



Lethal outcome of Covid-19 pneumonia in a new liver recipient with neurological manifestation

Pegah Eslami, Muhammadhosein Moradi, Arash Dooghaie Moghadam, Ali Pirsalehi, Shabnoor Abdul Lateef , Behandokht Rezaei, Amirreza Hadaegh, Amir sadeghi, hamid Asadzadeh Aghdaei, Mohammad reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020


Covid-19 is a new contagious viral pneumonia with various signs and symptoms including, loss of consciousness, liver injury, and cerebrovascular accident, however, there are little data about manifestation and outcome of COVID-19 in the liver transplant patients. Also, according to the closing of transplant units in Iran from the first day of the COVID-19 pandemic, we don’t have accurate data about nosocomial COVID-19 and liver transplant settings. In this article, we introduced a liver transplant recipient with final fatal outcome, who have had neurological manifestation. and also COVID-19 manifestations were started within 2 days after transplant surgery in the hospital.

Unusual gastrointestinal manifestations of COVID-19: two case reports

Amir Hossein Hassani, Alireza Beheshti, Faezeh Almasi , Pardis ketabi Moghaddam, Mohammadreza Azizi, Shabnam Shahrokh

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

Unusual gastrointestinal manifestations of COVID-19: Two case reports
Running heading: Unusual GI manifestations of two Covid-19 patients
Amir Hossein Hassani, Alireza Beheshti, Faezeh Almasi , Pardis ketabi Moghaddam, Mohammadreza Azizi, Shabnam Shahrokh
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Presentation of COVID-19 in a liver transplant recipient

Behzad Hatami, Pardis Ketabi Moghadam, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

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.

Letter to Editor

Covid-19 gastrointestinal symptoms are not a secondary clinical manifestation: the Italian experience

Roberto Assandri, Alessandro Montanelli

Gastroenterology and Hepatology from Bed to Bench, , 20 September 2020

After December 2019 outbreak in China, the novel Coronavirus infection has quickly overflowed worldwide and now considered the world public health crisis and the world breaking new. At May 2020 a total of 104291 laboratory-confirmed cases had been documented in Italy and Lombardy is the Northern Italian Region that major recorder to Covid-19 cases (over 62000 cases) [Ministry of Health, Civil Protection Department , daily notice].

In very recent work we showed that of 10% patients had GS symptoms, confirming the rate described in a Chinese cohorts

We demonstrated that GS symptoms presented on 4.9 days before hospital admission. Also we showed that the GS range onset is very wide with up to 20 days before admission, confirming that GS could be the first signal of Covid-19 infection

Our data also confirm the importance of including GS symptoms among the spectrum of Covid-19 features, to take early diagnosis and appropriate treatments, even in patients without respiratory symptoms.

We have read with great interest the manuscript by[1] which uses statistical models to predict the mortality due to Covid-19 for Italy, Iran and South Korea for the next month from 3/15/2020. It was claimed that the distribution of mortality was Poisson so the corresponding methods were used for performing simulations [2]. Now the actual values of mortality have released by WHO for the prediction period and the simulations showed an acceptable prediction but we would like to raise some comments.

Figure 1 shows the Rate ratios (actual rate/prediction rate) in Italy, South Korea and Iran. Rate ratios shows an overestimation of mortality rate in Italy (0.78, 0.65, 0.77) and South Korea (0.83, 0.77, 0.83) but an underestimation in Iran (1, The best predictions as expected were duo to next 10-Day of forecast. Although the same pattern of errors in predictions were occurred for Italy and South Korea, but The relative bias [3] of number of deaths (-0.29) and confirmed cases (-0.04) shows that the overestimation of mortality rate in Italy was duo to under estimation of number of deaths. But in South Korea the relative bias showed that over estimation were the results of over estimation of confirmed cases (0.48) not under estimation of number of deaths (0.14).

Relative ratios showed that predictions in Iran was lower than actual reports (figure 1). Relative bias of number of deaths was remarkably underestimated (0.35) but the number of confirmed cases was almost similar to real ones (-0.03).

The all three models were utilizing the same scenario and the results of predictions Iran was differed.  Thus it seems that number of deaths due to Covid-19 in Iran were reported less. The number of predictions of confirmed cases were very acceptable thus the hypothesis of reported deaths from Iran were lower than real ones become stronger.

Dear Editor,

We have read with great interest the study by Shojaee et al. (1) entitled “predicting the mortality due to covid-19 by the next month for Italy, Iran and South Korea; a simulation study”. During this study, the authors precisely estimated the number of laboratory confirmed covid-19 patients and the rate of death among three countries in the next month using a “Poisson” distribution.

Poisson distribution is the common discrete probability distribution for the modeling of counts data. This type of distribution assumes an equi-dispersion of data (2). The equi-dispersion results when the variance and the mean are equal.

However, in the real life, the populations are usually non-uniform (heterogeneous) and for several count data, the mean is not necessarily equal to that variance. This phenomenon is called as a problem of over-dispersion (3).  Endo et al. (4) findings indicated that the distribution of COVID-19 infection is highly over-dispersed.

It has been suggested that the most appropriate approach to deal with the problem of over-dispersion is using the “negative binomial” (NB) distribution. The NB distribution can be utilized for over-dispersed count data, when the conditional variance is higher than the conditional mean (2).  If the distribution of the outcome variable is over-dispersed, then the confidence intervals (CIs) for the negative binomial distribution are probably to be narrower than those derived from a Poisson distribution.

In conclusion, we suggest to simulate the mortality rate in COVID-19 studies using the “negative binomial” distribution. This distribution could provide more flexible functional forms than Poison distribution to accommodate over-dispersion.