The gut microbiome: a missing link in understanding the gastrointestinal manifestations of COVID-19?

Coronavirus disease 2019 (COVID-19), which is caused by infection with SARS-CoV-2, presents with a broad constellation of both respiratory and nonrespiratory symptoms, although it is primarily considered a respiratory disease. Gastrointestinal symptoms-including nausea, abdominal pain, vomiting, and diarrhea-rank chief among these. When coupled with the presence of viral RNA in fecal samples, the presence of gastrointestinal symptoms raises relevant questions regarding whether SARS-CoV-2 can productively infect the upper or lower gastrointestinal tract. Despite the well-documented prevalence of gastrointestinal symptoms and the high rate of SARS-CoV-2 fecal RNA shedding, the biological, clinical, and epidemiological relevance of these findings is unclear. Furthermore, the isolation of replication-competent virus from fecal samples has not been reproducibly and rigorously demonstrated. Although SARS-CoV-2 shedding likely occurs in a high proportion of patients, gastrointestinal symptoms affect only a subset of individuals. Herein, we summarize what is known about gastrointestinal symptoms and fecal viral shedding in COVID-19, explore the role of the gut microbiome in other respiratory diseases, speculate on the role of the gut microbiota in COVID-19, and discuss potential future directions. Taking these concepts together, we propose that studying gut microbiota perturbations in COVID-19 will enhance our understanding of the symptomology and pathophysiology of this novel devastating disease.

A dog's dinner: an interesting case presenting as gastroenteritis.

We report a case of a 60-year-old Caucasian man with a history of alcohol excess who presented to the emergency department with a 72-hour history of abdominal pain, profuse diarrhoea and vomiting. He was admitted to the intensive care unit (ICU) 12 hours later in extremis with severe sepsis and multiorgan failure. Collateral history from the patient on admission to ICU identified that he had been bitten by a dog 3 days prior to his symptom onset. Provisional microscopy and Gram staining from peripheral blood cultures taken on admission revealed the presence of long, thin Gram-negative bacilli in the anaerobic bottle only. This was later identified as Capnocytophaga canimorsus The patient survived the septic episode and was discharged to level 2 care 9 days later under the care of the renal physicians for ongoing renal dialysis.

Epidemiology, aetiology and seasonality of infectious diarrhoea in adult outpatients through active surveillance in Shanghai, China, 2012-2016: a cross-sectional study.

OBJECTIVES: This study aimed to identify the epidemiology, clinical characteristics, aetiology and seasonality of sporadic infectious diarrhoea in adults in Shanghai. SETTING: This study was based on a city-wide, active continuous hospital-based diarrhoea surveillance network established by Shanghai Municipal Center for Disease Control and Prevention. There were 22 sentinel hospitals in all 16 districts (9 primary-level hospitals, 6 secondary-level hospitals and 7 tertiary-level hospitals) which were selected using probability proportionate to size sampling method. PARTICIPANTS: From 1 May 2012 to 31 May 2016, 90 713 patients were included in this study. Among 8797 patients whose stool samples were collected and detected, 4392 patients were male. RESULTS: The positive rate was 47.96%. Bacterial and viral infections accounted for 27.19% and 69.07% separately. Norovirus was the most common pathogen (43.10%), followed by rotavirus, Vibrio parahaemolyticus, diarrhoeagenic Escherichia coli (DEC) and Salmonella spp. Patients between 30-44 and 45-59 years were more likely to have infectious diarrhoea and viral diarrhoea. Those aged 30-44 years were the most likely to get infected with V. parahaemolyticus (adjusted OR, aOR vs 60+ years: 2.04, 95% CI 1.47 to 2.78) and norovirus (aOR vs 60+ years: 1.32, 95% CI 1.12 to 1.56). Bacterial (except V. parahaemolyticus) diarrhoea was characterised by fever, abdominal pain and loose stool; while viral diarrhoea was characterised by nausea, vomiting and watery stool. A seasonal distribution of infectious diarrhoea was observed with larger peaks in winter and smaller peaks in summer. Winter peaks were mainly due to norovirus and rotavirus, and summer peaks were due to bacterial infections. An emerging spring peak of norovirus around March was observed in the past 3 years. CONCLUSION: Viral infections were predominant, and norovirus played a leading role. A seasonal distribution was observed and an emerging spring peak of norovirus was noted. Our findings highlight the necessity for conducting an active, comprehensive surveillance in adults, to monitor changing dynamics in the epidemiology and aetiology of infectious diarrhoea.

Bacteraemia and liver abscess due to Fusobacterium necrophorum.

Fusobacterium necrophorum is the oropharyngeal pathogen usually associated with Lemierre's syndrome, a pharyngeal infection which evolves to sepsis, septic emboli and thrombophlebitis of the adjacent neck vessels. It is an uncommon causative bacteria of a liver abscess, and an extensive workup should, therefore, be performed in order to rule out potential sources of the infection. This case report describes the workup that led to the diagnosis of a colorectal carcinoma, which was deemed to be the source of the Fusobacterium bacteraemia.

Disseminated cat-scratch disease presenting as nausea, diarrhea, and weight loss without fever in a heart transplant recipient.

We report the case of an afebrile 59-year-old heart transplant recipient presenting with nausea, vomiting, diarrhea, weight loss, and diffuse lymphadenopathy. Lymph node biopsies revealed non-caseating granulomatous inflammation. Cat-scratch disease was confirmed by serologic studies, Warthin-Starry staining, and polymerase chain reaction testing of lymph node tissue. The patient's symptoms resolved with 3 months of doxycycline. We review clinical presentations of Bartonella henselae infection and review diagnostic approaches for B. henselae in this patient population.

Changes in patients' symptoms and gastric emptying after Helicobacter pylori treatment.

AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients. METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori)-negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.

An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli.

BACKGROUND: Experimental human challenge models have played a major role in enhancing our understanding of infectious diseases. Primary outcomes have typically utilized overly simplistic outcomes that fail to entirely account for complex illness syndromes. We sought to characterize clinical outcomes associated with experimental infection with enterotoxigenic Escherichia coli (ETEC) and to develop a disease score. METHODS: Data were obtained from prior controlled human ETEC infection studies. Correlation and univariate regression across sign and symptom severity was performed. A multiple correspondence analysis was conducted. A 3-parameter disease score with construct validity was developed in an iterative fashion, compared to standard outcome definitions and applied to prior vaccine challenge trials. RESULTS: Data on 264 subjects receiving seven ETEC strains at doses from 1x105 to 1x1010 cfu were used to construct a standardized dataset. The strongest observed correlation was between vomiting and nausea (r = 0.65); however, stool output was poorly correlated with subjective activity-impacting outcomes. Multiple correspondence analyses showed covariability in multiple signs and symptoms, with severity being the strongest factor corresponding across outcomes. The developed disease score performed well compared to standard outcome definitions and differentiated disease in vaccinated and unvaccinated subjects. CONCLUSION: Frequency and volumetric definitions of diarrhea severity poorly characterize ETEC disease. These data support a disease severity score accounting for stool output and other clinical signs and symptoms. Such a score could serve as the basis for better field trial outcomes and gives an additional outcome measure to help select future vaccines that warrant expanded testing in pivotal pre-licensure trials.

Helicobacter pylori infection is high in paediatric nonulcer dyspepsia but not associated with specific gastrointestinal symptoms.

AIM: The association between Helicobacter pylori infection and gastrointestinal symptoms is debatable in childhood. We examined the potential relationship between H. pylori infection and gastrointestinal symptoms in Brazilian children with nonulcer dyspepsia. METHODS: This prospective observational study analysed 240 Brazilian children and adolescents (68.7% girls) with chronic nonulcer dyspepsia, who underwent upper gastrointestinal endoscopy and biopsy. Their mean age was 9.8 years (range 4-17). Upper gastrointestinal symptoms, including abdominal pain, nausea, burning, early satiety, belching and weigh loss, were evaluated by a questionnaire and H. pylori infection was determined by histopathology of gastric biopsies. RESULTS: H. pylori infection was identified in 123/240 patients (52%). There was no significant association between the H. pylori infection and gastrointestinal symptoms and no relationship between the infection and abdominal pain or pain characteristics. However, nausea was significantly associated with the H. pylori infection, with an odds ratio of 1.76 and 95% confidence interval of 1.1-2.94 p < 0.03. Symptoms lasting longer than 12 months were significantly more frequent in children with pangastritis than in those with antral gastritis (p < 0.05). CONCLUSION: The prevalence of H. pylori infection was high in Brazilian children with nonulcer dyspepsia, but was not associated with specific signs and symptoms, except for nausea.

Clinical information on admission is insufficient to determine the appropriate isolation regimen for acute gastroenteritis.

INTRODUCTION: The number of admissions for acute gastroenteritis (GE) is increasing. The majority of patients pass through a single high-flow emergency department (ED) area which increases the risk of spreading GE. The aim of this study was to determine the frequency and aetiology of GE for acutely admitted patients and to analyse their clinical information focusing on risk indicators of contagious aetiology and on the chosen isolation regime to determine if the GE required a contact precaution isolation regime. MATERIAL AND METHODS: This study included patients above 16 years of age who were admitted acutely within a one-year study period to a Danish hospital with a catchment population of 231,000 persons. The following items were analysed: information from the referring doctor, diarrhoea, nausea and vomiting and fever history, abdominal pain, prior antibiotics, co-morbidity, drugs, travel history, contagious contacts, general condition, vital values, isolation regime, final diagnosis and results of stool examination. RESULTS: Among 17,531 acute admissions, 1.6% had acute GE and 60% of these had stool examinations performed. Only 35% of the patients with GE had information about possible GE at referral. Short duration and vomiting may help to identify norovirus and antibiotic treatment within the last month to identify Clostridium difficile infections. All patients with highly infective GE were isolated under a contact precaution regime, but only one in four of the isolated patients were actually highly contagious. CONCLUSION: Acute GE is a prevalent condition in the ED; a number of patients are isolated unnecessarily, but it is difficult to assess correctly who should be isolated and who should not. We recommend that further studies be undertaken to define isolation criteria and to assess the usefulness of new rapid analysis modalities with a view to reducing the isolation period. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

The cellular mechanisms of the antiemetic action of dexamethasone and related glucocorticoids against vomiting.

Glucocorticoids, used primarily as anti-allergic and anti-inflammatory drugs, are also effective, alone or combined with other antiemetics, for preventing nausea and vomiting. Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting, and in patients with only one or two risks for postoperative nausea and vomiting (PONV). Dexamethasone combined with 5-HT3 or tachykinin NK1 antagonists is also suggested for higher-level emetogenic chemotherapy and radiotherapy and for patients at high risk for PONV. Glucocorticoids may act via the following mechanisms: (1) anti-inflammatory effect; (2) direct central action at the solitary tract nucleus, (3) interaction with the neurotransmitter serotonin, and receptor proteins tachykinin NK1 and NK2, alpha-adrenaline, etc.; (4) maintaining the normal physiological functions of organs and systems; (5) regulation of the hypothalamic-pituitary-adrenal axis; and (6) reducing pain and the concomitant use of opioids, which in turn reduces opioid-related nausea and vomiting.

Relationship between symptoms and gastric emptying of solids in functional dyspepsia.

OBJECTIVE: Functional dyspepsia is a heterogeneous disorder and different pathophysiological mechanisms underlie its symptom patterns. This study investigated the relationship between dyspepsia symptoms and overall and proximal gastric emptying in patients with functional dyspepsia. METHODS: A total of 93 patients with functional dyspepsia and 32 healthy subjects were enrolled in this cross-sectional study. Prevalence and severity of eight dyspepsia symptoms were recorded. Gastric emptying was measured using single photon emission computed tomography scanning. RESULTS: Overall and proximal gastric emptying were delayed in 47.3% (44/93) and 46.2% (43/93) of the patients, respectively. Logistic regression analyses showed that presence of nausea was associated with delayed proximal gastric emptying (odds ratio 4.951; 95% confidence interval 1.321, 18.558). There were no significant differences between normal and delayed overall gastric emptying according to presence of symptoms. CONCLUSIONS: Presence of nausea might indicate delayed gastric emptying of the proximal stomach. Promotion of proximal gastric emptying may constitute an effective therapy for patients with functional dyspepsia who report nausea as the dominant symptom.

[Clinical and morphological features in a case of recent gastric carcinoma (the signet ring cell carcinoma type)]. / Particularitati clinico-morfologice într-un caz de carcinom gastric incipient (tipul de carcinom în inel cu pecete).

The article presents the case of a male patient, hospitalized due to severe pain in the upper abdomen area, nausea, and vomiting. The patient was diagnosed with surgical acute abdomen, for which emergency surgery is performed. Upon penetration into the peritoneal cavity, stomach inspection shows at the medio-gastric level, on the greater curvature, a callous gastric ulcer, with a central perforation. A large excision is decided up to the healthy (normal) gastric tissue, and the resulting pieces are sent to the pathological anatomy laboratory. The histopathological exam reveals signet ring cell recent gastric carcinoma. The biopsy performed 1 month after surgery, prelevated from the antropyloric zone, reveals antropyloric gastritis with moderate activity and Helicobacter pylori positive. Due to the fact that such cases when this gastric cancer type is diagnosed in recent stages are extremely rare, we considered it useful to present it and look into its macroscopic and microscopic aspects, as well as into the differentiating diagnosis.

The EGFR expression in gastric mucosa of children infected with Helicobacter pylori.

PURPOSE: Epidermal growth factor receptor (EGFR) modulates balance between proliferation and apoptosis in gastric mucosa of the gastrointestinal tract. The aim of the study was to evaluate immunohistochemically the EGFR expression in epithelial and gland cells of antral mucosa in children infected with Helicobacter pylori (H. pylori). MATERIAL/METHODS: The study included 44 children, aged from 5 to 18 years (mean age 13+/-3.4 years) with dyspeptic symptoms, of whom 30 (68.2%) children were infected with H. pylori, 14 (31.8%) children constituted controls. Endoscopic and histopathological assessment of antral mucosa samples was performed according to the Sydney System. Samples taken from gastroscopy were prepared to evaluate EGFR expression in epithelial and gland cells of antrum mucosa according to the manual of a detection kit of EnVision+System-HRP (DAKO). RESULTS: In children H. pylori infected, the EGFR expression in epithelial cells of antral mucosa equaled on average 82.5+/-15 cells/mm2 and ranged from 45.0 to 98.0 cells/mm2 as well as differed statistically significantly when compared to controls (10.2+/-5.0 cells/mm2) (p<0.001). In children with H. pylori infection, the EGFR expression in gland cells of antral mucosa ranged from 2.0 to 85.0 cells/mm2 (mean 25.7+/-22.6 cells/mm2); was lower and differed statistically significantly from controls (54.2 +/- 29.6 cells/mm2) (p<0.001). In children H. pylori infected, there was a statistically significant difference (p<0.001) between the EGFR expression in epithelial and in gland cells of antral mucosa. CONCLUSION: The increased EGFR expression in epithelial cells in comparison with gland cells of antral mucosa in children with H. pylori infection may suggest its role in regeneration processes of gastric mucosa.