The impact of the coronavirus (COVID-19) pandemic on individuals with gastrointestinal disorders: A protocol of an international collaborative study.

OBJECTIVE: The COVID-19 pandemic has had a significant impact on mental health across the globe. People living with a chronic gastrointestinal (GI) disorder might be particularly at risk of mental health complications given higher rates of comorbid anxiety and depression compared to the healthy population. As GI disorders affect up to 40% of the population worldwide, this international collaborative study seeks to evaluate the extent of the impact of the COVID-19 pandemic on GI symptoms specifically and more generally on the well-being of those living with chronic GI conditions. METHODS: A longitudinal survey with three time points (baseline, 6-month, and 12-month) will be conducted online. Adult participants with GI disorders from multiple countries will be recruited via patient associations, social media advertising, utilizing snowball sampling. Participants will be invited to complete a battery of questionnaires including demographic and health parameters, and measures of gastrointestinal symptoms, fear of COVID-19, perceived impact of COVID-19, illness perceptions, coping, depression, anxiety, stress, catastrophizing, and quality of life, using validated measures where available. Statistical analyses will include univariate descriptive models, multivariate models utilizing regression, mediation, and moderation, and latent growth models. CONCLUSIONS: This project may present novel information to the field of psychogastroenterology and may provide crucial information regarding the areas of impact for individuals with GI disorders during and following the pandemic. Further, this information can guide healthcare providers and patient associations on how to target support related to the pandemic mental health sequelae for these patients.

COVID-19 in gastroenterology: Where are we now? Current evidence on the impact of COVID-19 in gastroenterology.

BACKGROUND: The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients. OBJECTIVE: At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context. METHODS/RESULTS/CONCLUSION: We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.

Implications of SARS-CoV-2 infection for neurogastroenterology.

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

Abnormal Nailfold Capillaroscopy in a Patient With Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is an emerging entity during the coronavirus disease 2019 pandemic. Medium- and large-vessel changes are present in MIS-C; however, microcirculatory impairment has not been documented. We report a case of MIS-C in a toddler that presented with persistent fever, gastrointestinal symptoms and rash. Nailfold videocapillaroscopy was abnormal, suggesting microcirculatory disease in the setting of MIS-C.

COVID-19 Associated Multisystem Inflammatory Syndrome: A Systematic Review and Meta-analysis.

The prevalence of multisystem inflammatory syndrome in children (MIS-C) has increased since the coronavirus disease 2019 (COVID-19) pandemic started. This study was aimed to describe clinical manifestation and outcomes of MIS-C associated with COVID-19. This systematic review and meta-analysis were conducted on all available literature until July 3rd, 2020. The screening was done by using the following keywords: ("novel coronavirus" Or COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus) and ("MIS-C" or "multisystem inflammatory" or Kawasaki). Data on gender, ethnicity, clinical presentations, need for mechanical ventilation or admission to intensive care unit (ICU), imaging, cardiac complications, and COVID-19 laboratory results were extracted to measure the pooled estimates. Out of 314 found articles, 16 articles with a total of 600 patients were included in the study, the most common presentation was fever (97%), followed by gastrointestinal symptoms (80%), and skin rashes (60%) as well as shock (55%), conjunctivitis (54%), and respiratory symptoms (39%). Less common presentations were neurologic problems (33%), and skin desquamation (30%), MIS-C was slightly more prevalent in males (53.7%) compared to females (46.3%). The findings of this meta-analysis on current evidence found that the common clinical presentations of COVID-19 associated MIS-C include a combination of fever and mucocutaneous involvements, similar to atypical Kawasaki disease, and multiple organ dysfunction. Due to the relatively higher morbidity and mortality rate, it is very important to diagnose this condition promptly.

Impact of COVID-19 lockdown on symptoms in patients with functional gastrointestinal disorders: Relationship with anxiety and perceived stress.

BACKGROUND: Psychological stress and anxiety, such those generated by forced quarantine, affect gastrointestinal symptoms course in patients with functional gastrointestinal disorders. Thus, our aim was to assess, in a cohort of patients regularly followed up in a devoted outpatient clinic of Southern Italy, the association between their gastrointestinal symptoms changes, stress, and anxiety reported during the Italian lockdown. METHODS: We recruited patients from the outpatient clinic of the University of Salerno, devoted to functional gastrointestinal disorders, selecting only patients for whom an evaluation was available in the last 6 months before the lockdown. Gastrointestinal symptoms were evaluated at each visit through standardized questionnaire and pooled in a database. On 45th days from the beginning of the lockdown, patients were re-assessed by phone with the same questionnaire. Anxiety and stress levels were assessed through a self-administered online questionnaire based on Generalized Anxiety Disorder 7 test and Perceived Stress Scale 10 test. KEY RESULTS: The intensity-frequency scores of several upper gastrointestinal symptoms improved (Wilcoxon test <0.05). Higher anxiety levels had a higher risk of worsening chest pain (OR 1.3 [1.1-1.7]), waterbrash (OR 1.3 [1.0-1.7]), epigastric burning (OR 1.3 [1.0-1.6]), and abdominal pain (OR 1.6 [1.0-2.3]). When compared to the interval preceding the outbreak, half of the patients declared their symptoms remained unchanged, 13.6% worsened, and 36.4% improved. CONCLUSIONS AND INFERENCES: During the COVID-19 quarantine, there was an improvement of the majority of upper gastrointestinal symptoms in our patients, and anxiety seems an important risk of worsening few of them.

Digestive system manifestations and clinical significance of coronavirus disease 2019: A systematic literature review.

BACKGROUND AND AIM: A worldwide outbreak of coronavirus disease 2019 (COVID-19) has drawn global attention. Several reports have described the gastrointestinal (GI) manifestations in the infected patients. The systematic review was designed to highlight the gaps in our knowledge about the prevalence and clinical significance of GI symptoms in patients with COVID-19. METHODS: We searched PubMed database and Google articles published in both English and Chinese up to June 3, 2020, using search terms "clinical features," "2019 novel coronavirus," "2019-nCoV," "COVID-19," or "SARS-Cov-2." Observational studies, case reports, or letters describing the clinical features or observational studies regarding the detection and/or isolation of severe acute respiratory syndrome coronavirus 2 viruses in stools were included. RESULTS: A total of 22 publications were finally selected. It was reported that GI symptoms occurred in about 3-40.7% of patients. GI manifestations included nausea, diarrhea, anorexia, vomiting, abdominal pain, belching, abdominal distension, and GI hemorrhage. Diarrhea was the most common GI symptom. Infected patients had various degrees of liver dysfunction, and the severity of liver dysfunction was significantly associated with the severity of the disease. Therapy focusing on digestive system like liver supportive therapy or nutrition support or probiotics has been demonstrated to be effective interventions, which greatly improve prognosis. Fecal-oral transmission route is a potential risk for transmission. CONCLUSIONS: GI symptoms are common in COVID-19. Strengthening the recognition on abnormalities in digestive system of patients with COVID-19 is crucial for early identification and timely treatment, especially for those atypical patients. Hygiene protection and keeping the drainpipe free flowing are necessary for everyone.

[Gastrointestinal and hepatic manifestations of COVID-19 in children]. / Manifestaciones gastrointestinales y hepáticas de COVID-19 en niños.

SARS-CoV-2 is a high environmental stable virus. It is predominantly a respiratory pathogen that also affects the gastrointestinal tract. The ACE 2 receptor is the main receptor of SARS-CoV-2, with evidence of its high presence in the intestine, colon and cholangiocytes, and, in smaller proportion, in hepatocytes. SARS-CoV-2 has a gastrointestinal tropism that explains digestive symptoms and viral spread in stools. The characteristics of this virus include the S (Spike) protein that binds very stably to the ACE-2 receptor and, at the same time, SARS-CoV-2 produces dysbiosis and alterations in the gut-lung axis. It produces a clear T-cell response and a cytokines storm in the intestine and liver that would produce inflammatory bowel damage. Intestinal manifestations by order of frequency are loss of appetite, diarrhea, nausea and vomiting, and abdominal pain, where the latter could be a severity marker. In children, diarrhea is the most frequent symptom, usually mild and self-limiting. In the liver, hypertransaminasemia occurs in severe patients ranging from 40 to 60%. SARS-CoV-2 can re main in stools longer than in respiratory secretions, which would influence the spread of disease. This article highlights the importance of an early diagnosis of gastrointestinal and hepatic manifestations, increase the index of suspicion, make a timely diagnosis, and recognize eventual complications of the disease. The potential oral-fecal route of transmission may influence the disease spread. Recognizing this finding is important to define isolation.

Acute gastrointestinal injury in critically ill patients with COVID-19 in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. Most critically ill patients have organ injury, including acute respiratory distress syndrome, acute kidney injury, cardiac injury, or liver dysfunction. However, few studies on acute gastrointestinal injury (AGI) have been reported in critically ill patients with COVID-19. AIM: To investigate the prevalence and outcomes of AGI in critically ill patients with COVID-19. METHODS: In this retrospective study, demographic data, laboratory parameters, AGI grades, clinical severity and outcomes were collected. The primary endpoints were AGI incidence and 28-d mortality. RESULTS: From February 10 to March 10 2020, 83 critically ill patients out of 1314 patients with COVID-19 were enrolled. Seventy-two (86.7%) patients had AGI during hospital stay, of these patients, 30 had AGI grade I, 35 had AGI grade II, 5 had AGI grade III, and 2 had AGI grade IV. The incidence of AGI grade II and above was 50.6%. Forty (48.2%) patients died within 28 days of admission. Multiple organ dysfunction syndrome developed in 58 (69.9%) patients, and septic shock in 16 (19.3%) patients. Patients with worse AGI grades had worse clinical variables, a higher incidence of septic shock and 28-d mortality. Sequential organ failure assessment (SOFA) scores (95%CI: 1.374-2.860; P < 0.001), white blood cell (WBC) counts (95%CI: 1.037-1.379; P = 0.014), and duration of mechanical ventilation (MV) (95%CI: 1.020-1.340; P = 0.025) were risk factors for the development of AGI grade II and above. CONCLUSION: The incidence of AGI was 86.7%, and hospital mortality was 48.2% in critically ill patients with COVID-19. SOFA scores, WBC counts, and duration of MV were risk factors for the development of AGI grade II and above. Patients with worse AGI grades had a higher incidence of septic shock and 28-d mortality.

Coronaviruses and gastrointestinal diseases.

The effects of coronaviruses on the respiratory system are of great concern, but their effects on the digestive system receive much less attention. Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting. Available data have shown that human coronaviruses, including the newly emerged SARS-CoV-2, mainly infect the respiratory system and cause symptoms such as cough and fever, while they may generate gastrointestinal symptoms. However, there is little about the relation between coronavirus and digestive system. This review specifically addresses the effects of mammalian and human coronaviruses, including SARS-CoV-2, on the digestive tract, helping to cope with the new virus infection-induced disease, COVID-19.

Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms in Northern Italy: A Single-Center Cohort Study.

INTRODUCTION: The most typical presentation of COVID-19 is an acute respiratory syndrome whose most common symptoms include fever, cough, and dyspnea. However, gastrointestinal symptoms, such as diarrhea and nausea/vomiting, are increasingly reported in patients affected by COVID-19. This study aimed to describe the prevalence and time of onset of gastrointestinal symptoms in patients affected by COVID-19 and to find potential associations between gastrointestinal symptoms and clinical outcomes. METHODS: We performed a prospective single-center cohort study, enrolling patients who received diagnosis of COVID-19 at our institution between March 23, 2020, and April 5, 2020. We collected patient demographics and medical history, laboratory data, and clinical outcomes. Furthermore, we used a specifically designed questionnaire, administered to patients at time of diagnosis, to obtain data on the presence and time of onset of fever, typical respiratory symptoms, gastrointestinal symptoms, and other symptoms (fatigue, headache, myalgia/arthralgia, anosmia, ageusia/dysgeusia, sore throat, and ocular symptoms). RESULTS: In our cohort, 138 (69%) of 190 patients showed at least 1 gastrointestinal symptom at diagnosis; if excluding hyporexia/anorexia, 93 patients (48.9%) showed at least 1 gastrointestinal symptom. Gastrointestinal symptoms, in particular diarrhea, were associated with a lower mortality. At multivariate analysis, diarrhea was confirmed as independent predictive factor of lower mortality. DISCUSSION: Gastrointestinal symptoms are very frequent in patients with COVID-19 and may be associated with a better prognosis. These data suggest that, in some patients, the gastrointestinal tract may be more involved than the respiratory system in severe acute respiratory syndrome coronavirus 2 infection, and this could account for the less severe course of disease.

Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes.

BACKGROUND: Globally, the current medical emergency for novel coronavirus 2019 (COVID-19) leads to respiratory distress syndrome and death. PURPOSE: This review highlighted the effect of COVID-19 on systemic multiple organ failure syndromes. This review is intended to fill a gap in information about human physiological response to COVID-19 infections. This review may shed some light on other potential mechanisms and approaches in COVID -19 infections towards systemic multiorgan failure syndromes. FINDING: SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism). This may be aggravated by cytokine storm with the extensive release of proinflammatory cytokines from the deregulating immune system. CONCLUSION: The widespread and vicious combinations of cytokines with organ crosstalk contribute to systemic hyper inflammation and ultimately lead to multiple organ dysfunction (Fig. 1). This comprehensive study comprises various manifestations of different organs in COVID-19 and may assist the clinicians and scientists pertaining to a broad approach to fight COVID 19.

Gastrointestinal implications in COVID-19.

Believed to have originated from a local Huanan Seafood Wholesale Market in Wuhan, Hubei Province in China, the COVID-19 has had an unprecedented and catastrophic impact on humanity, with the WHO declaring it a global pandemic. Although the first case of COVID-19 was reported in December 2019, the primary source and intermediate host have not been confirmed, but human-to-human transmission has been universally accepted. The main mode of transmission of the virus is through respiratory droplets along with prominent respiratory system involvement. However, fecal-oral transmission due to the shedding of the virus in the gastrointestinal (GI) tract may continue for up to 10 weeks after respiratory clearance and is fast becoming important. SARS-CoV-2 shows a high affinity to ACE2 receptors, making sites of high ACE2 receptor expression, such as lungs, GI tract, brain, kidneys, heart, liver and immune system, a prime target for infection. Through this literature review, we aim to summarize the current knowledge of immunological pathways that contribute to the disease with a focus specifically on the GI tract involvement. We direct attention to the pathophysiological mechanism of involvement of the GI tract leading to symptomatic manifestations, track GI organ-specific viral loads to compare and contrast with other organ systems. We briefly detail specific treatment strategies from a GI disease standpoint and mention special considerations when there is involvement of the GI tract.

Multisystem effects of COVID-19: a concise review for practitioners.

While COVID-19 has primarily been characterized by the respiratory impact of viral pneumonia, it affects every organ system and carries a high consequent risk of death in critically ill patients. Higher sequential organ failure assessment (SOFA) scores have been associated with increased mortality in patients critically ill patients with COVID-19. It is important that clinicians managing critically ill COVID-19 patients be aware of the multisystem impact of the disease so that care can be focused on the prevention of end-organ injuries to potentially improve clinical outcomes. We review the multisystem complications of COVID-19 and associated treatment strategies to improve the care of critically ill COVID-19 patients.

COVID-19 pandemic: Pathophysiology and manifestations from the gastrointestinal tract.

The pandemic of coronavirus disease 2019 (COVID-19), caused by a newly identified ß-coronavirus (SARS-CoV-2) has emerged as a dire health problem, causing a massive crisis for global health. Primary method of transmission was firstly thought to be animal to human transmission. However, it has been observed that the virus is transmitted from human to human via respiratory droplets. Interestingly, SARS-CoV-2 ribonucleic acid (RNA) has been isolated from patient stools, suggesting a possible gastrointestinal (GI) involvement. Most commonly reported clinical manifestations are fever, fatigue and dry cough. Interestingly, a small percentage of patients experience GI symptoms with the most common being anorexia, diarrhea, nausea and vomiting. The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples. The exact incidence of digestive symptoms is a matter of debate. The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms' mechanism. Cases with solely GI symptoms have been reported in both adults and children. Viral RNA has also been detected in stool and blood samples, indicating the possibility of liver damage, which has been reported in COVID-19 patients. The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis, however data from these cases is lacking. The aim of this review is firstly, to briefly update what is known about the origin and the transmission of SARS-CoV-2, but mainly to focus on the manifestations of the GI tract and their pathophysiological background, so that physicians on the one hand, not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other, to have SARS-CoV-2 on their mind when the "gastroenteritis" type symptoms predominate.

American Neurogastroenterology and Motility Society Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic.

The American Neurogastroenterology and Motility Society Task Force recommends that gastrointestinal motility procedures should be performed in motility laboratories adhering to the strict recommendations and personal protective equipment (PPE) measures to protect patients, ancillary staff, and motility allied health professionals. When available and within constraints of institutional guidelines, it is preferable for patients scheduled for motility procedures to complete a coronavirus disease 2019 (COVID-19) test within 48 hours before their procedure, similar to the recommendations before endoscopy made by gastroenterology societies. COVID-19 test results must be documented before performing procedures. If procedures are to be performed without a COVID-19 test, full PPE use is recommended, along with all social distancing and infection control measures. Because patients with suspected motility disorders may require multiple procedures, sequential scheduling of procedures should be considered to minimize need for repeat COVID-19 testing. The strategies for and timing of procedure(s) should be adapted, taking into consideration local institutional standards, with the provision for screening without testing in low prevalence areas. If tested positive for COVID-19, subsequent negative testing may be required before scheduling a motility procedure (timing is variable). Specific recommendations for each motility procedure including triaging, indications, PPE use, and alternatives to motility procedures are detailed in the document. These recommendations may evolve as understanding of virus transmission and prevalence of COVID-19 infection in the community changes over the upcoming months.

The effect of emergency surgery on acute abdomen patients with COVID-19 pneumonia: a retrospective observational study.

During the COVID-19 outbreak, some patients with COVID-19 pneumonia also suffered from acute abdomen requiring surgical treatment; however, there is no consensus for the treatment of such patients. In this study, we retrospectively reviewed 34 patients with acute abdomen who underwent emergency surgery during the COVID-19 outbreak. Among the 34 patients with acute abdomen, a total of six cases were found with COVID-19 pneumonia (clinical classification for COVID-19 pneumonia: all were the common type). On the premise of similar demographics between both groups, patients with COVID-19 pneumonia had worse indicators of liver and coagulation function. Compared with acute abdomen patients without COVID-19, patients with COVID-19 pneumonia had a longer hospital stay, but there were no significant differences in postsurgical complications (P = 0.58) or clinical outcomes (P = 0.56). In addition, an obvious resolution of lung inflammation after surgery was observed in five COVID-19 patients (83.3%). No new COVID-19 cases occurred during the patients' hospital stays. Therefore, for the common type of COVID-19 pneumonia, emergency surgery could not only improve the outcomes of COVID-19 pneumonia patients with acute abdomen, but also benefit the resolution of pulmonary inflammation.