Impact of COVID-19 on the digestive system: A descriptive cross-sectional study

Background: Various digestive symptoms caused by COVID-19 are frequently reported. This study aims to describe the most frequent digestive signs in patients with COVID-19, the relationship between the severity of digestive symptoms and some serological markers associated with liver manifestation, the detection of SARS-CoV-2 in a stool sample, and the mortality rate of those patients. Material(s) and Method(s): A descriptive cross-sectional study on 100 confirmed COVID-19 cases with digestive and hepatic manifestation in one center (Fallujah Teaching Hospital), Anbar governorate, Iraq, during a period of study. Questioner's data were formed for all patients regarding age, sex, and comorbidities such as diabetes and hypertension. Liver function enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, total bilirubin (TBIL), and direct bilirubin and haematological parameters such as ferritin D-dimer, C-reactive protein (CRP), albumin, amylase, leukocyte count, and prothrombin time were used. SARS-CoV-2 prevalence in stool is determined using reverse transcription polymerase chain reaction according to manufacturer's instructions. The mortality rate of patients with COVID-19 was also determined. Data were followed up until April 22, 2022. Result(s): Patients with digestive symptoms who had COVID-19 had an average age of 45.03 (SD 20.078), 52 (52%) were men, and 48 (48%) were women. No statistically significant variances were observed in the severity of digestive symptoms among age groups. The three digestive symptoms that patients with COVID-19 experienced most frequently were fatigue, fever, and abdominal colic. SARS-CoV-2 was detected in the stool of 11% of the patients with COVID-19 with digestive signs. The COVID-19 mortality rate was 9%. Statistically, significant variance was observed in ALT (P value 0.01) and TBIL (P value 0.0027) levels between mild, moderate, and severe gastrointestinal (GI) diseases. The levels of CRP varied considerably among those with mild, moderate, and severe GI conditions (P value 0.0182, according to the findings). In mild, moderate, and severe GI disorders, ferritin levels differed considerably (P value 0.05). Conclusion(s): The faecal sample with a nasopharyngeal swab is needed to confirm COVID-19 diagnosis;hepatic manifestations are connected with increased COVID-19 mortality in individuals with digestive symptoms.Copyright © 2022 Wahab, Khalil, Majeed, licensee HBKU Press.

Risk factors for the development of hepatic manifestations in COVID-19 patients with digestive symptoms

Background: Abnormalities in liver function tests (LFTs) are found in 14%-53% of hospitalized COVID-19 patients. These could occur in patients with or without previous chronic liver diseases. Knowing the risk factor of liver manifestations in COVID-19 subjects is crucial for the proper management of these patients. Objective(s): We aimed to identify the risk factors for liver manifestations as well as other risk factors in COVID-19 subjects who complained of digestive manifestations. Material(s) and Method(s): COVID-19 patients with and without liver manifestations at the Emergency Department of Al Fallujah Teaching Hospital were enrolled in this study. This study covered a period from September 15, 2022, to April 22, 2022. Comparisons between patients with or without abnormal LFTs were made. The possible risk variables connected to abnormal LFTs and hepatic manifestation were investigated using univariable and multivariable logistic regression analysis. Result(s): Out of 100 COVID-19 patients, there were 64 suffering from mild gastrointestinal (GI) symptoms. There were 26 mild cases with abnormal LFTs (40.6%). Although there were nine (total number 22) and seven (total number 14) of the moderate and severe cases with liver involvement, there was no statistically significant difference between the digestive manifestations severity and liver involvement. Increased alanine aminotransferase (ALT) levels were linked to a greater incidence of LFTs, according to multivariable analysis (odds ratio [OR]: 45.05;P < 0.0001), elevated aspartate aminotransferase (AST;OR: 3.462;P = 0.00041), elevated direct bilirubin (DBIL) (OR: 3.643;P < 0.001), and elevated d-dimer levels [OR]: 2.690;P < 0.0137) in liver involvement group compared with non-involvement patients. Conclusion(s): Elevated ALT, AST, DBIL, and d-dimer are potential risk factors for liver manifestations in COVID-19 patients with digestive symptoms.

Impact of COVID-19 on the digestive system: A descriptive crosssectional study

Background: Various digestive symptoms caused by COVID-19 are frequently reported. This study aims to describe the most frequent digestive signs in patients with COVID-19, the relationship between the severity of digestive symptoms and some serological markers associated with liver manifestation, the detection of SARS-CoV-2 in a stool sample, and the mortality rate of those patients. Material(s) and Method(s): A descriptive cross-sectional study on 100 confirmed COVID-19 cases with digestive and hepatic manifestation in one center (Fallujah Teaching Hospital), Anbar governorate, Iraq, during a period of study. Questioner's data were formed for all patients regarding age, sex, and comorbidities such as diabetes and hypertension. Liver function enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, total bilirubin (TBIL), and direct bilirubin and haematological parameters such as ferritin D-dimer, Creactive protein (CRP), albumin, amylase, leukocyte count, and prothrombin time were used. SARS-CoV-2 prevalence in stool is determined using reverse transcription polymerase chain reaction according to manufacturer's instructions. The mortality rate of patients with COVID-19 was also determined. Data were followed up until April 22, 2022. Result(s): Patients with digestive symptoms who had COVID-19 had an average age of 45.03 (SD 20.078), 52 (52%) were men, and 48 (48%) were women. No statistically significant variances were observed in the severity of digestive symptoms among age groups. The three digestive symptoms that patients with COVID-19 experienced most frequently were fatigue, fever, and abdominal colic. SARS-CoV-2 was detected in the stool of 11% of the patients with COVID-19 with digestive signs. The COVID-19 mortality rate was 9%. Statistically, significant variance was observed in ALT (P value 0.01) and TBIL (P value 0.0027) levels between mild, moderate, and severe gastrointestinal (GI) diseases. The levels of CRP varied considerably among those with mild, moderate, and severe GI conditions (P value 0.0182, according to the findings). In mild, moderate, and severe GI disorders, ferritin levels differed considerably (P value 0.05). Conclusion(s): The faecal sample with a nasopharyngeal swab is needed to confirm COVID-19 diagnosis;hepatic manifestations are connected with increased COVID-19 mortality in individuals with digestive symptoms.

Digestive system infection by SARS­CoV­2: Entry mechanism, clinical symptoms and expression of major receptors (Review).

Besides causing severe acute respiratory syndrome (SARS), SARS­coronavirus 2 (SARS­CoV­2) also harms the digestive system. Given the appearance of numerous cases of SARS­CoV­2, it has been demonstrated that SARS­CoV­2 is able to harm target organs such as the gastrointestinal tract, liver and pancreas, and either worsen the condition of patients with basic digestive illnesses or make their prognosis poor. According to several previously published studies, angiotensin­converting enzyme II (ACE2) and transmembrane serine protease II (TMPRSS2) are expressed either singly or in combination in the digestive system and in other regions of the human body. In order to change the viral conformation, create a fusion hole and release viral RNA into the host cell for replication and transcription, SARS­CoV­2 is capable of binding to these two proteins through the spike protein on its surface. As a result, the body experiences an immune reaction and an inflammatory reaction, which may lead to nausea, diarrhea, abdominal pain and even gastrointestinal bleeding, elevated levels of liver enzymes, acute liver injury, pancreatitis and other serious lesions. In order to provide possible strategies for the clinical diagnosis and treatment of digestive system diseases during the COVID­19 pandemic, the molecular structure of SARS­CoV­2 and the mechanism via which SARS­CoV­2 enters the human body through ACE2 and TMPRSS2 were discussed in the present review, and the clinical manifestations of SARS­CoV­2 infection in the digestive system were also summarized. Finally, the expression characteristics of ACE2 and TMPRSS2 in the main target organs of the digestive system were described.

Using search trends before and after the COVID-19 outbreak in China to analyze digestive symptoms: medical informatics study of the Baidu Index data.

Background: From the beginning of 2020, the world was plunged into a pandemic caused by the novel coronavirus disease-19 (COVID-19). People increasingly searched for information related to COVID-19 on internet websites. The Baidu Index is a data sharing platform. The main data provided is the search index (SI), which represents the frequency that keywords are used in searches. Methods: January 9, 2020 is an important date for the outbreak of COVID-19 in China. We compared the changes of SI before and after for 7 keywords, including "fever", "cough", "nausea", "vomiting", "abdominal pain", "diarrhea", "constipation". The slope and peak values of SI change curves are compared. Ten provinces in China were selected for a separate analysis, including Beijing, Gansu, Guangdong, Guangxi, Heilongjiang, Hubei, Sichuan, Shanghai, Xinjiang, Tibet. The change of SI was analyzed separately, and the correlation between SI and demographic and economic data was analyzed. Results: During period I, from January 9 to January 25, 2020, the average daily increase (ADI) of the SI for "diarrhea" was lower than that for "cough" (889.47 vs. 1,799.12, F=11.43, P=0.002). In period II, from January 25 to April 8, 2020, the average daily decrease (ADD) of the SI for "diarrhea" was significantly lower than that for "cough", with statistical significance (cough, 191.40 vs. 441.44, F=68.66, P<0.001). The mean SI after January 9, 2020 (pre-SI) was lower than that before January 9, 2020 (post-SI) (fever, 2,616.41±116.92 vs. 3,724.51±867.81, P<0.001; cough, 3,260.04±308.43 vs. 5,590.66±874.25, P<0.001; diarrhea, 4,128.80±200.82 vs. 4,423.55±1,058.01, P<0.001). The pre-SI mean was correlated with population (P=0.004, R=0.813) and gross domestic product (GDP) (P<0.001, R=0.966). The post-SI peak was correlated with population (P=0.007, R=0.789), GDP (P=0.005, R=0.804), and previously confirmed cases (PCC) (P=0.03, R=0.670). The growth rate of the SI was correlated with the post-SI peak (P=0.04, R=0.649), PCC (P=0.003, R=0.835). Conclusions: Diarrhea was of widespread concern in all provinces before and after the COVID-19 outbreak and may be associated with novel coronavirus infection. Internet big data can reflect the public's concern about diseases, which is of great significance for the study of the epidemiological characteristics of diseases.

Prevalence and Severity of Gastrointestinal Symptoms in COVID-19 Patients in Casablanca: A Retrospective Cohort Study.

Background The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), is behind the current pandemic. At the start of the pandemic, gastrointestinal symptoms initially described as rare were reported, but their spread to other countries increased rapidly. This study aimed to determine the prevalence of digestive symptoms among COVID-19 patients and to assess the correlation between these symptoms and disease severity. Methods This retrospective observational study was conducted in the Cheikh Khalifa University Hospital of Casablanca, Morocco. Patients were divided into two groups based on the presence or absence of gastrointestinal symptoms upon initial assessment and hospital admission. Results A total of 154 patients were included in this study from March 21 to April 26, 2020. The mean age of patients was about 48.5 (± 20.0) years, and 85 (55.2%) of them were men. In our population, 8.17% of patients had toxic habits. Digestive symptoms were present at admission in 30% of our patients. The most frequent digestive symptoms were diarrhea (15%), abdominal pain (5.6%), vomiting (5%), and anorexia (3.1%). We found a significant difference in COVID-19 patients with digestive symptoms and toxic habits contrary to all other comorbidities. Neurologic symptoms were significantly associated (p=0,004) with digestive symptoms in 50%. Conclusion In this study, we found that digestive symptoms were present in 22.64% of patients diagnosed with COVID-9. The clinician must know the different digestive symptoms to evoke the diagnosis and take charge of the patient early.

Digestive manifestations in hospitalized patients with COVID-19

Introduction: COVID-19 has caused an unprecedented health crisis, as it is an emerging, unprecedented disease with high transmissibility. New different strains from the original variant of the virus have already been identified, which could mean a change in its clinical presentation patterns. Objective: To describe the digestive manifestations in patients hospitalized due to COVID-19. Methods: A descriptive, prospective study was carried out in patients diagnosed with COVID-19, admitted among the months of July and September 2021;136 patients were studied. Each selected patient had the individual medical record compiled. The variables taken into consideration were sex, age, comorbidities, presence of digestive manifestations and duration of digestive symptoms. The average and standard deviation for the duration of the digestive symptoms were calculated, and in the remaining variables, the results were expressed in absolute frequency and percentages. Results: Digestive manifestations were present in 58,8 % of the patients. Diarrhea occurred in 29,4 %, a with an average duration of approximately 1,9 days, and was the earliest digestive symptom of all those identified. Nausea and anorexia occurred in 25 %;anorexia was the symptom that lasted the longest, with a maximum of 10 days. Conclusions: The digestive manifestations in hospitalized patients with COVID-19 were diarrhea, nausea, vomiting, epigastric pain, anorexia and dyspepsia, of which the most frequent presentation was: diarrhea, nausea and anorexia. © 2022, Editorial Ciencias Medicas. All rights reserved.

Effect of a Daily Collagen Peptide Supplement on Digestive Symptoms in Healthy Women: 2-Phase Mixed Methods Study.

BACKGROUND: The effect of dietary collagen on managing digestive symptoms is currently lacking in the literature. OBJECTIVE: To gain a better understanding of this issue, we conducted a 2-phase mixed methods study. METHODS: Phase 1 was a mixed methods design to explore current attitude and practice among consumers and health care practitioners. The findings were used to design an 8-week phase 2 digital study called Gutme! conducted in the United States in healthy female volunteers (BMI>25 kg/m2). Our aim was, first, to determine the feasibility of conducting a fully digital mixed methods study; second, the study explored the effect of an 8-week daily supplementation of 20 g dietary collagen peptide (Peptan) on digestive symptoms. Phase 2 was a prospective, open-label, longitudinal, single-arm study. Participation involved 2 weeks of baseline tracking (digestive symptoms, mood, stool, and lifestyle) using an app, followed by 8 weeks of tracking and taking 20 g collagen peptide supplement split into 2 dosages per day. Participants were required to complete a web-based symptom questionnaire at baseline, week 2, and week 8, as well as participate in 2 scheduled video interviews. RESULTS: Phase 1 revealed that consumer awareness of collagen for digestive health is low (64/204, 31.4%). Among the dietitians prescribing collagen for their patients, the most common dosage was 20 g a day with notable effects after 6 weeks of intake. Within the phase 2 study, of the 40 recruited participants, 14 (35%) completed the full course of supplementation. The findings indicate that 93% (13/14) of those who completed the study experienced a reduction in digestive symptoms, which included bloating. CONCLUSIONS: A mixed methods digital study design is feasible and acceptable for collecting relevant data in a real-life setting. The use of a 20 g daily collagen peptide supplement may reduce bloating and improve mild digestive symptoms in otherwise healthy female adults in the absence of any other dietary or lifestyle interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04245254; https://clinicaltrials.gov/ct2/show/NCT04245254.

Significance of digestive symptoms after COVID-19 vaccination: A retrospective single-center study.

OBJECTIVE: There is insufficient research on digestive symptoms and outcomes following coronavirus disease (COVID-19) vaccination. We aimed to investigate digestive symptoms and related complications among South Koreans who were administered COVID-19 vaccines. METHODS: Forty-six patients (men: 22, women: 24) with a median age of 68 years (interquartile range:55.5, 73.8 years) who experienced digestive symptoms following COVID-19 vaccination between March 1 and July 30, 2021, were included. This retrospective single-center study collected information on clinical symptoms, laboratory tests, imaging results, comorbidities, complications, treatment type, and prognosis. RESULTS: Thirty-three (71.7%), nine (19.6%), and three (6.5%) patients were administered AZD1222 (AstraZeneca), BNT162b2 (Pfizer/BioNTech), and JNJ-78436735 (Johnson and Johnson) vaccines, respectively. Patients were classified with mild (25 patients, 54.3%), moderate (five patients, 10.9%), and severe (16 patients, 34.8%) based on disease severity. Digestive symptoms included abdominal pain, diarrhea, dyspepsia, and nausea, which usually developed within 1 day (78.3%) following the first vaccination. In total, 14 (30.4%) patients experienced only gastrointestinal symptoms, whereas 32 (69.6%) experienced non-gastrointestinal symptoms. Complications included enterocolitis (76%), acute kidney injury (9%), anaphylactoid reaction (2%), and duodenal perforation (2%). CONCLUSIONS: COVID-19 vaccines caused digestive symptoms and other complications that ranged from mild to severe. While further validation is required, our results suggest that monitoring digestive symptoms following COVID-19 vaccination can help detect rather severe complications that require medical intervention.

Gastrointestinal symptoms and the severity of COVID-19: Disorders of gut-brain interaction are an outcome.

BACKGROUND: Many of the studies on COVID-19 severity and its associated symptoms focus on hospitalized patients. The aim of this study was to investigate the relationship between acute GI symptoms and COVID-19 severity in a clustering-based approach and to determine the risks and epidemiological features of post-COVID-19 Disorders of Gut-Brain Interaction (DGBI) by including both hospitalized and ambulatory patients. METHODS: The study utilized a two-phase Internet-based survey on: (1) COVID-19 patients' demographics, comorbidities, symptoms, complications, and hospitalizations and (2) post-COVID-19 DGBI diagnosed according to Rome IV criteria in association with anxiety (GAD-7) and depression (PHQ-9). Statistical analyses included univariate and multivariate tests. RESULTS: Five distinct clusters of symptomatic subjects were identified based on the presence of GI symptoms, loss of smell, and chest pain, among 1114 participants who tested positive for SARS-CoV-2. GI symptoms were found to be independent risk factors for severe COVID-19; however, they did not always coincide with other severity-related factors such as age >65 years, diabetes mellitus, and Vitamin D deficiency. Of the 164 subjects with a positive test who participated in Phase-2, 108 (66%) fulfilled the criteria for at least one DGBI. The majority (n = 81; 75%) were new-onset DGBI post-COVID-19. Overall, 86% of subjects with one or more post-COVID-19 DGBI had at least one GI symptom during the acute phase of COVID-19, while 14% did not. Depression (65%), but not anxiety (48%), was significantly more common in those with post-COVID-19 DGBI. CONCLUSION: GI symptoms are associated with a severe COVID-19 among survivors. Long-haulers may develop post-COVID-19 DGBI. Psychiatric disorders are common in post-COVID-19 DGBI.

Gastrointestinal manifestations with COVID-19 virus infection: A Moroccan prospective study.

BACKGROUND AND STUDY AIMS: Gastrointestinal manifestations are common during coronavirus disease (COVID-19) infection. They can occur before respiratory symptoms, resulting in a diagnostic delay and an increased risk of disease transmission. The current study reports major gastrointestinal manifestations as initial symptoms of COVID-19. PATIENTS AND METHODS: This prospective, descriptive, cross-sectional, and single-center study of 713 cases was conducted in a field hospital in Morocco over a 5-week period from June 21 to July 25, 2020. RESULTS: The average age of our patients was 31.95 years. Clinically, on admission, anorexia was the main symptom, present in 32.3% of patients. Gastrointestinal manifestations were present in 14.9% of patients, including watery diarrhea in 8.6% of cases, nausea and/or vomiting in 4.6% of cases, and abdominal pain in 1.6% of cases. Six hundred thirty-two patients were treated in accordance with one of the two therapeutic protocols recommended by the National Ministry of Health. The treatment-related effects that occurred in 61.4% of patients were primarily digestive in 55.3% of cases. In multivariate analysis, following adjustment of the studied parameters, only the presence of gastrointestinal manifestations (odds ratio [OR]: 1.478 confidence interval [CI]: 1.286-1.698; p < 0.001) and treatment side effects (OR = 1.069, CI: 1.020-1.119, p = 0.005) altered the rate of negative polymerase chain reaction (PCR) tests on day 10. CONCLUSION: Gastrointestinal manifestations are common during COVID-19 and seem to be linked to a longer duration of disease. SARS-CoV-2 (the causative virus of COVID-19) can persist in the digestive tract, with the possibility of fecal-oral transmission. Therefore, hygiene is extremely important, especially handwashing and strict precautions when performing gastrointestinal endoscopy and handling stools from infected patients.

COVID-19 inpatients with gastrointestinal onset: sex and care needs' differences in the district of Ferrara, Italy.

BACKGROUND: COVID-19 is characterized by interstitial pneumonia, but a presentation of the disease with digestive symptoms only may occur. This work was aimed at evaluating: (1) the prevalence of presentation with digestive symptoms only in our cohort of COVID-19 inpatients; (2) differences between patients with and without gastrointestinal onset; (3) differences among males and females with gastrointestinal presentation; (4) outcomes of the groups of subjects with and without gastrointestinal onset. METHOD: We retrospectively divided the patients hospitalized with COVID-19 into two groups: (1) the one with digestive symptoms (DSG) and (2) the other without digestive symptoms (NDSG). We compared the subjects of DSG with those of NDSG and males with females in the DSG group only, in terms of demographics (age, sex), inflammation and organ damage indexes, length of stay, in-hospital and 100-day mortality. RESULTS: The prevalence of gastrointestinal symptoms at presentation was 12.5%. The DSG group showed a prevalence of females, and these tended to a shorter hospital stay; DSG patients were younger and with a higher load of comorbidities, but no differences concerning inflammation and organ damage indexes, need for intensification of care, in-hospital and 100-day mortality were detected. Among DSG patients, males were younger than females, more comorbid, with higher serum CRP and showed a longer length of hospital stay. Survival functions of DSG patients, in general, are more favourable than those of NDSG if adjusted for sex, age and comorbidities. CONCLUSIONS: (1) The prevalence of gastrointestinal presentation among hospitalized COVID-19 patients was 12.5%; (2) DSG patients were on average younger, more comorbid and with a prevalence of females, with a shorter hospital stay; (3) in the DSG group, males had a higher Charlson Comorbidity Score and needed a longer hospital stay; (4) DSG subjects seem to survive longer than those of the NDSG group.

Gastrointestinal and hepatic abnormalities in patients with confirmed COVID-19: A systematic review and meta-analysis.

Although not common, gastrointestinal and liver symptoms have reportedly been the initial presentation of coronavirus disease-2019 (COVID-19) in a large group of patients. Therefore, knowing the frequency and characteristics of these manifestations of COVID-19 is important for both clinicians and health policy makers. A systematic review and meta-analysis of the available data on the gastrointestinal and liver manifestations of patients with COVID-19 was performed. PubMed and Scopus databases and Google Scholar search engine were searched for published and unpublished preprint articles up to 10 April 2020. Original studies providing information on clinical digestive symptoms or biomarkers of liver function in patients with polymerase chain reaction confirmed diagnosis of COVID-19 were included. After quality appraisal, data were extracted. Prevalence data from individual studies were pooled using a random-effects model. Overall, 67 studies were included in this systematic review and meta-analysis, comprising a pooled population of 13 251 patients with confirmed COVID-19. The most common gastrointestinal symptoms were anorexia (10.2%, 95% confidence interval [CI] = 6.2%-16.4%), diarrhea (8.4%, 95% CI = 6.2%-11.2%), and nausea (5.7%, 95% CI = 3.7%-8.6%), respectively. Decreased albumin levels (39.8%, 95% CI = 15.3%-70.8%), increased aspartate aminotransferase (22.8%, 95% CI = 18.1%-28.4%), and alanine aminotransferase (20.6%, 95% CI = 16.7%-25.1%) were common hepatic findings. After adjusting for preexisting gastrointestinal (5.9%) and liver diseases (4.2%), the most common gastrointestinal findings were diarrhea (8.7%, 95% CI = 5.4%-13.9%), anorexia (8.0%, 95% CI = 3.0%-19.8%), and nausea (5.1%, 95% CI = 2.2%-14.3%). Gastrointestinal and liver manifestations are not rare in patients with COVID-19, but their prevalence might be affected by preexisting diseases. Diarrhea and mild liver abnormalities seem to be relatively common in COVID-19, regardless of comorbidities.

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

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.

Digestive symptoms and liver injury in patients with coronavirus disease 2019 (COVID-19): A systematic review with meta-analysis.

Although most COVID-19 patients typically present with respiratory symptoms, many patients could experience digestive symptoms as the major complaint. We performed a systematic review and meta-analysis to investigate the exact prevalence of digestive symptoms and liver injury in COVID-19 patients and compare the difference between patients with and without digestive symptoms. PubMed, Embase, Ovid, Wanfang data, and CNKI were searched until 24 April 2020 to identify studies that reported digestive symptoms and liver injury in COVID-19 patients. A random-effect model was used to combine the data. Finally, 64 studies with 15 141 patients were included. The pooled rate of digestive symptoms and liver dysfunction was 31.8% (95 CI 21.0-42.5%, I 2 = 97.6%) and 27.4% (95 CI 16.9-37.9%, I 2 = 97.9%), respectively. Patients with digestive symptoms were more likely to present with fatigue (OR 2.28, 95 CI 1.66-3.14, P < 0.00001, I 2 = 31%), myalgia (OR 1.96, 95 CI 1.06-3.65, P = 0.03, I 2 = 69%), and acute respiratory disease syndrome (ARDS) (OR 2.94, 95 CI 1.17-7.40, P = 0.02, I 2 = 0) and had a trend to present as severe/critical type (OR 1.87, 95 CI 0.98-3.57, P = 0.06, I 2 = 58%). Severe/critical patients were more likely to present with diarrhea (OR 2.02, 95 CI 1.16-3.50, P = 0.01, I 2 = 64) and have high alanine aminotransferase (ALT) (OR 2.08, 95 CI 1.55-2.81, P < 0.00001, I 2 = 13%,) and aspartate aminotransferase (AST) (OR 3.53, 95 CI 2.76-4.51, P < 0.00001, I 2 = 0). The pooled rate of patients with digestive symptoms was 28.7% (95 CI 17.6-39.8%) and 42.8% (95 CI 23.4-62.3%) in studies from China and out of China, respectively. COVID-19 patients had a high rate of digestive symptoms and liver injury. Patients with digestive symptoms had a trend to develop severe/critical illness.

Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients.

COVID-19 is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structural protein on its surface called the S-spike. Further, cleavage of the viral spike protein (S) by the proteases like transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) is essential to effectuate host cell membrane fusion and virus infectivity. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variations of SARS-CoV-2 cell entry related receptors expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients. Based on the human tissue specific distribution of SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 and other supportive evidence from the literature, we hypothesize that SARS-CoV-2 host cell entry receptor-ACE2 based mechanism in GI tissue may be involved in COVID-19 (i) in the pathogenesis of digestive symptoms, (ii) in increased diabetic complications, (iii) in disease recurrence.

The digestive system and the COVID-19.

The current pandemic coronavirus disease (COVID-19) is an ongoing healthcare crisis. While COVID- 19 typically presents as fever and respiratory illness, almost 50% of the patients also have associated digestive symptoms which vary from abdominal pain to diarrhoea and indigestion. Literature review of association of COVID- 19 with digestive symptoms was done using Google search and the results are presented herein.