A global multicenter propensity-matched analysis of mortality risk and palliative care referral due to cirrhosis in hospitalized patients with COVID-19.

Background and Aim: A few recent studies identified cirrhosis as a risk factor for high mortality in patients with coronavirus disease-19 (COVID-19). Palliative care is less often involved in the management of cirrhosis. We analyzed a global multicenter database to study the risk of mortality and palliative care referrals in patients with COVID-19 and cirrhosis. Methods: A federated cloud-based network (TriNetX) data from 50 health-care organizations across the globe were analyzed retrospectively. Patients with COVID-19 aged from 18 years to 90 years were identified between January 20, 2020, and November 16, 2020. Results: A total of 1969 patients (Group A) with COVID-19 and cirrhosis and 169,257 patients with COVID-19 alone (Group B) were studied. The two groups had a similar occurrence of other comorbid diseases. In a propensity-matched analysis, the mortality rate in Group A (8.9%) was significantly higher than Group B (5.6%), hazard ratio (95% confidence interval) for mortality with cirrhosis was 1.59 (1.26-1.99) (P = 0.01). The occurrence of palliative care referrals in Group A (4.1%) was significantly higher than Group B (2.0%), hazard ratio (95% confidence interval) with cirrhosis was 2.02 (1.39-2.94) (P = 0.01). Conclusion: Mortality rate and palliative care referrals were higher in patients with cirrhosis and COVID-19 compared to those with COVID-19 alone. This increased occurrence of palliative care referrals compared to the general trend in cirrhotic patients probably indicates increased awareness of COVID-19 as a life-threatening condition. Relevance for Patients: Cirrhosis should be identified as a high-risk condition that may require palliative care referral in hospitalized patients with COVID-19. Hospital resource utilization and cost-analysis modeling should anticipate the need for palliative care referrals as a significant outcome in patients with cirrhosis who are hospitalized with COVID-19.

Pre-hospitalization proton pump inhibitor use and clinical outcomes in COVID-19.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 may escape the inactivation by gastric acid because of hypochlorhydria caused by proton pump inhibitors (PPIs), which could predispose the patients to severe COVID-19. METHODS: We studied the association between prehospitalization PPI exposure and clinical outcomes among hospitalized COVID-19 patients. RESULTS: A total of 295 hospitalized COVID-19 patients were included in the study. 15.6% of hospitalized COVID-19 patients were on PPIs at home. Mortality among PPI-users was 2.3 times higher than non-users, along with 2.3 times higher risk of acute respiratory distress syndrome after adjusting for confounding variables. CONCLUSION: We found that prehospitalization PPI-exposure is independently associated with worse clinical outcomes, including mortality in COVID-19 patients, regardless of the presence of cardiovascular comorbidities.

Red Blood Cell Distribution Width in Hospitalized COVID-19 Patients.

Introduction: Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is causing dramatic morbidity and mortality worldwide. The Red Blood Cell Distribution Width (RDW) has been strongly associated with increased morbidity and mortality in multiple diseases. Objective: To assess if elevated RDW is associated with unfavorable outcomes in hospitalized COVID-19. Methods: We retrospectively studied clinical outcomes of hospitalized COVID-19 patients for their RDW values. In-hospital mortality was defined as primary outcome, while septic shock, need for mechanical ventilation, and length of stay (LOS) were secondary outcomes. Results: A total of 294 COVID-19 patients were finally studied. Overall prevalence of increased RDW was 49.7% (146/294). RDW was associated with increased risk of in-hospital mortality (aOR, 4.6; 95%CI, 1.5-14.6) and septic shock (aOR, 4.6; 95%CI, 1.4-15.1) after adjusting for anemia, ferritin, lactate, and absolute lymphocyte count. The association remained unchanged even after adjusting for other clinical confounders such as age, sex, body mass index, coronary artery disease, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease. No association was found instead with mechanical ventilation and median LOS. Conclusion: Elevated RDW in hospitalized COVID-19 patients is associated with a significantly increased risk of mortality and septic shock.

COVID-19 and the liver: a narrative review of the present state of knowledge.

Novel corona virus disease (COVID-19) is an ongoing pandemic that has spread across the globe. The virus primarily infects type-2 pneumocytes in alveoli and causes lung disease, with severity ranging from mild pneumonia to acute respiratory distress syndrome. The virus also invades gastrointestinal epithelial cells, hepatocytes, and biliary epithelial cells. Derangement of liver function tests is noted in about one third of patients and appears to correlate with more severe disease. There are multiple mechanisms by which the virus can cause liver injury; immune-mediated inflammation and direct viral cytotoxicity are believed to be the predominant mechanisms. Liver injury appears to be transient, usually recovering with resolution of illness. Limited available studies and experience from prior corona virus pandemics seem to suggest that immunosuppressed patients have similar outcomes compared to non-immunosuppressed patients. Age and comorbid conditions seem to influence outcome, irrespective of immune status. Additionally, patients with preexisting comorbid conditions are more prone to acquire infection and should strictly adhere to travel and social distancing advisories. Telemedicine should be utilized to provide uninterrupted care for patients with liver disease, and clinic or hospital visits should be advised only in sick patients with advanced liver disease. In conclusion, liver dysfunction is not uncommon in COVID-19, it generally improves with resolution of disease, and patients with chronic liver disease (CLD) need continued follow up, uninterrupted by the ongoing pandemic, preferably in virtual clinic settings.

Prevalence, Mechanisms, and Implications of Gastrointestinal Symptoms in COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The infection started as an outbreak of pneumonia-like symptoms in Wuhan, China. Within a few weeks, it spread across the entire globe resulting in millions of cases and thousands of deaths. While respiratory symptoms and complications are well-defined and can be severe, non-respiratory symptoms of COVID-19 are increasingly being recognized. Gastrointestinal manifestations such as nausea, vomiting, diarrhea, and abdominal pain have been added to the list of common COVID-19 symptoms. Their prevalence has been increasing, probably due to increased recognition and experience with the pandemic. Furthermore, diarrhea and stool testing may change prevalence and transmission rates due to suspicion for fecal-oral transmission of the COVID-19. Due to this risk, various countries have started testing wastewater and sewage systems to examine its role in the spread of SARS-CoV-2 among communities. In this review article, we describe the common gastrointestinal manifestations in COVID-19, their prevalence based upon the current literature, and highlight the importance of early recognition and prompt attention. We also note the role of fecal-oral transmission. Furthermore, the mechanisms of these symptoms, the role of medications, and potential contributing factors are also elaborated.

Successful Distancing: Telemedicine in Gastroenterology and Hepatology During the COVID-19 Pandemic.

Telemedicine involves delivering healthcare and preventative care services to patients without the need for in-person encounters. Traditionally, telemedicine has been used for acute events (e.g., stroke, used to relay essential information to the emergency department) and chronic disease management (e.g., diabetes and chronic kidney disease management). Though the utilization of telemedicine in gastroenterology and hepatology has been modest at best, especially for inflammatory bowel diseases and chronic liver disease management, since the onset of coronavirus disease 2019 (COVID-19) pandemic, utilization of telemedicine in gastroenterology increased by 4000% in the first two weeks, equivalent to the last six years of growth before the pandemic. The Center for Medicare and Medicaid (CMS) relaxed rules for the use of telemedicine with easing restrictions on reimbursements, location, licensing requirements (across state lines), and the need for a prior provider-patient relationship. These changes increased the use of telemedicine in inpatient and outpatient settings for gastroenterology-related referrals. The use of inpatient telephonic or video consults helps provide timely care during the pandemic while conserving personal protective equipment and decreasing provider and patient exposure. Nevertheless, telehealth use comes at the cost of no direct patient contact and lesser reimbursements. The appropriate use of technology and equipment, training of healthcare providers, use of platforms that can be integrated into the electronic health record while protecting the privacy and the flow of information are essential components of telemedicine. Furthermore, encouraging patients to seek medical care remotely with the proper equipment and improving digital literacy without the need for physical examinations is a challenge, further compounded in elderly or hard-of-hearing patients and in patients who are more comfortable with in-person visits. The authors will systematically review and discuss how telemedicine can be integrated into the practice of gastroenterology and hepatology, with emphasis placed on discussing barriers to success and the ways they can be mitigated.

The Association of "Loss of Smell" to COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: The presence of olfactory dysfunction or "loss of smell" has been reported as an atypical symptom in patients with coronavirus disease 2019 (COVID-19). We performed a systematic review and meta-analysis of the available literature to evaluate the prevalence of "loss of smell" in COVID-19 as well as its utility for prognosticating the disease severity. METHODS: An exhaustive search of the PubMed/Medline, Embase, Web of Science, Cochrane Library, LitCovid NIH, and WHO COVID-19 database was conducted through August 6th, 2020. All studies reporting the prevalence of "loss of smell" (anosmia and/or hyposmia/microsmia) in laboratory-confirmed COVID-19 patients were included. Pooled prevalence for cases (positive COVID-19 through reverse transcriptase (RT-PCR) and/or serology IgG/IgM) and controls (negative RT-PCR and/or serology) was compared, and the odds ratio (OR), 95% confidence interval (CI) and the p-value were calculated. A p-value of <0.05 was considered statistically significant. RESULTS: A total of 51 studies with 11074 confirmed COVID-19 patients were included. Of these, 21 studies used a control group with 3425 patients. The symptom of "loss of smell" (OR: 14.7, CI: 8.9-24.3) was significantly higher in the COVID-19 group when compared to the control group. Seven studies comparing severe COVID-19 patients with- and without "loss of smell" demonstrated favorable prognosis for patients with "loss of smell" (OR: 0.36, CI 0.27-0.48). CONCLUSIONS: Olfactory dysfunction or "loss of smell" is a prevalent symptom in COVID-19 patients. Moreover, COVID-19 patients with "loss of smell" appear to have a milder course of the disease.

Gastrointestinal Endoscopy in the Era of COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which led to a worldwide pandemic that started in early 2020. Healthcare systems across the world encountered an unprecedented surge of COVID-19 patients resulting in more than half a million deaths globally. COVID-19 has affected multiple sub-specialties and procedure-related fields, including gastroenterology. Gastrointestinal (GI) endoscopy centers are specialized units where thousands of endoscopies are performed annually. A significant proportion of these procedures are affected due to the national and regional lockdowns across the globe. To adapt to this rapidly evolving situation, endoscopy centers have undergone significant changes and have taken unprecedented precautions to avoid the transmission of the virus. However, endoscopy centers are going through financial strain due to a reduction in the number of procedures from lockdowns and fear of virus transmission. Theoretically, endoscopies could add to the disease transmission as SARS-CoV-2 has shown to be present in the GI secretions. Multiple precautions such as mandatory use of face masks, safe distancing, use of barriers between the endoscopists and patients, negative pressure rooms, extended use of personal protective equipment, and volume reduction have been taken to decrease the risk of disease transmission by these centers. Moreover, pre-endoscopy COVID-19 testing has now become the norm. In this review, we highlight the significant changes assumed by the endoscopy center. Furthermore, we discuss cost-related concerns of pre-endoscopy COVID-19 testing, the downtime and delays related to the procedures, and effects of rescheduling. As the pandemic progresses through multiple phases, endoscopy centers should use a dynamic approach to adapt and strive to provide the best patient care.

Clinical Characteristics, Diagnosis, and Treatment of Major Coronavirus Outbreaks.

Human coronavirus infections have been known to cause mild respiratory illness. It changed in the last two decades as three global outbreaks by coronaviruses led to significant mortality and morbidity. SARS CoV-1 led to the first epidemic of the twenty first century due to coronavirus. SARS COV-1 infection had a broad array of symptoms with respiratory and gastrointestinal as most frequent. The last known case was reported in 2004. Middle East respiratory syndrome coronavirus (MERS-CoV) led to the second outbreak in 2012, and case fatality was much higher than SARS. MERS-CoV has a wide array of clinical presentations from mild, moderate to severe, and some patients end up with acute respiratory distress syndrome (ARDS). The third and recent outbreak by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in December 2019, which lead to a global pandemic. Patients with SARS-CoV2 infection can be asymptomatic or have a range of symptoms with fever, cough, and shortness of breath being most common. Reverse transcriptase-Polymerase chain reaction (RT-PCR) is a diagnostic test of choice for SARS CoV-1, MERS-CoV, and SARS CoV-2 infections. This review aims to discuss epidemiological, clinical features, diagnosis, and management of human coronaviruses with a focus on SARS CoV-1, MERS-CoV, and SARS CoV-2.

Addition of Tocilizumab to the Standard of Care Reduces Mortality in Severe COVID-19: A Systematic Review and Meta-Analysis.

Introduction: Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, concrete evidence of its benefit in reducing mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of TCZ in severe COVID-19 vs. standard of care (SOC) alone. Methods: A literature search for studies that compared "tocilizumab" and "standard of care" in the treatment of COVID-19 was done using major online databases from December 2019 to June 14, 2020. Search words "Tocilizumab," "anti-interleukin-6 antibody," and "COVID-19" or "coronavirus 2019" in various combinations were used. Articles in the form of abstracts, letters without original data, case reports, and reviews were excluded. Data were gathered on an Excel sheet, and statistical analysis was performed using Review Manager 5.3. Results: Sixteen studies were eligible from 693 initial studies, including 3,641 patients (64% males). There were 13 retrospective studies and three prospective studies. There were 2,488 patients in the SOC group (61.7%) and 1,153 patients (68.7%) in the TCZ group. The death rate in the TCZ group, 22.4% (258/1,153), was lower than in the SOC group, 26.21% (652/2,488) [pooled odds ratio 0.57 (95% CI 0.36-0.92), p = 0.02]. There was a significant heterogeneity (inconsistency index = 80%) among the included studies. Conclusion: The addition of TCZ to the SOC might reduce mortality in severe COVID-19. More extensive randomized clinical trials are needed to validate these findings.

Antibody tests for COVID-19.

The SARS-CoV-2 virus caused a globally growing pandemic called coronavirus disease 2019 (COVID-19) that has disrupted social, political, and medical environments around the world. Nations are assessing ways to reopen businesses while trying to balance health care risks and economic fallouts. Strategies involving antibody testing have been proposed before phased reopening of the economy. Therefore, assessing the sensitivity and specificity of antibody tests for symptomatic and asymptomatic COVID-19 patients remains paramount to prevent COVID-19 outbreaks. The antibody tests for SARS-CoV-2 detect the presence of IgA, IgM, or IgG antibodies produced by B cells. There are four major types of antibody tests: rapid diagnostic tests, enzyme-linked immunosorbent assays, neutralization assays, and chemiluminescent immunoassays. Currently, there is no standard antibody test for detecting SARS-CoV-2 antibodies during or after exposure or infection. The antibody tests for SARS-CoV-2 have a low specificity within the first week of exposure and increase in the second and third weeks. The current data on antibody tests have several limitations in quality and the presence of bias. Specifically, many antibody tests have a high false-negative rate and a high risk of bias for participant selection, application of index tests, reference standard used, and flow and timing for antibody tests that may incorrectly report the accuracy of COVID-19 antibody tests. In this review, we summarize the current methods, sensitivity/specificity, and gaps in knowledge concerning COVID-19 antibody testing.

Current and future implications of COVID-19 on gastroenterology training and clinical practice.

The novel coronavirus disease 2019 (COVID-19) pandemic has affected almost every country on the globe, affecting 185 countries with more than 2.6 million cases and 182,000 deaths as of April 22, 2020. The United States (US) has seen an exponential surge in the COVID-19 patients and has become the epicentre with more than 845,000 confirmed cases and 46,000 deaths. The governments and healthcare providers all over the world are racing with time to reduce the rate of increase in active cases by social distancing to flatten the curve of this pandemic. Practicing gastroenterologists are facing multiple challenges in the safe practice of medicine because of patient's inability to visit physicians' offices, endoscopy centers and the threat of potential virus spread through gastrointestinal secretions by endoscopies in emergent cases. The gastroenterological associations from Europe and North America have made position statements to guide gastroenterologists to navigate through the clinical practice during the COVID-19 pandemic. Gastroenterology fellows are on the frontlines during the COVID-19 pandemic, experiencing personal, physical and economic stresses. They had to balance the programmatic changes to meet the demands of the patient care with the additional pressure to meet training requirements. Given the imperatives for social and physical distancing, training programmes have to implement innovative educational methods to substitute traditional teaching. Healthcare organisations must synchronise institutional workforce needs with trainee safety, education and well-being. In this perspective, we have discussed the challenges that can be anticipated and implementing strategies to support fellows during the times of the COVID-19 pandemic.