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.

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.

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.

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.

COVID-19 in Cancer Patients From New York City: A Comparative Single Center Retrospective Analysis.

In this retrospective study we analyze and compare clinical characteristics and outcomes of patients with and without cancer history who were infected with novel coronavirus disease 19 (COVID-19). Medical records were reviewed and a comparative analysis of 53 cancer and 135 non-cancer patients with COVID-19 were summarized. Results: The median age for COVID-19 patients with and without cancer was 71.5 and 61.6 years, respectively. Patients aged 60 years and above were 86.8% and 60.7% in cancer and non-cancer groups, respectively. A high proportion of cases were seen in African Americans 73.6% (with cancer) and 75.6% (without cancer) followed by Hispanic patients. Male and female patients had a high percentage of prostate (39.3%) and breast (32%) cancer respectively. Prostate cancer (18.9%) and myeloma (11.3%) were common among solid and hematological cancers respectively. Hypertension and smoking were prevalent among cancer (83% and 41.5%) compared to non-cancer (67.4% and 9.6%) patients. The common symptoms in cancer patients were dyspnea (64.2%) followed by fever and cough (50.9%) compared to fever (68.1%) and cough (66.7%) in non-cancer patients. Cancer patients had higher levels of lactic acidosis, C-reactive protein, lactate dehydrogenase, and alkaline phosphatase than non-cancer patients (p < 0.05). Conclusions: Rapid clinical deterioration was seen in cancer patients who were aged 60 years and above. Higher mortality was seen in this subgroup, especially when they had associated hypertension and elevated levels of CRP and LDH.

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.

Gastrointestinal Symptoms and Outcomes in Hospitalized Coronavirus Disease 2019 Patients.

INTRODUCTION: Gastrointestinal (GI) symptoms are increasingly being recognized in coronavirus disease 2019 (COVID-19). It is unclear if the presence of GI symptoms is associated with poor outcomes in COVID-19. We aim to assess if GI symptoms could be used for prognostication in hospitalized patients with COVID-19. METHODS: We retrospectively analyzed patients admitted to a tertiary medical center in Brooklyn, NY, from March 18, 2020, to March 31, 2020, with COVID-19. The patients' medical charts were reviewed for the presence of GI symptoms at admission, including nausea, vomiting, diarrhea, and abdominal pain. COVID-19 patients with GI symptoms (cases) were compared with COVID-19 patients without GI symptoms (control). RESULTS: A total of 150 hospitalized COVID-19 patients were included, of which 31 (20.6%) patients had at least 1 or more of the GI symptoms (cases). They were compared with the 119 COVID-19 patients without GI symptoms (controls). The average age among cases was 57.6 years (SD 17.2) and control was 63.3 years (SD 14.6). No statistically significant difference was noted in comorbidities and laboratory findings. The primary outcome was mortality, which did not differ between cases and controls (41.9 vs. 37.8%, p = 0.68). No statistically significant differences were noted in secondary outcomes, including the length of stay (LOS, 7.8 vs. 7.9 days, p = 0.87) and need for mechanical ventilation (29 vs. 26.9%, p = 0.82). DISCUSSION: In our study, the presence of GI manifestations in COVID-19 at the time of admission was not associated with increased mortality, LOS, or mechanical ventilation.

Low morbidity and mortality with COVID-19 in sickle cell disease: A single center experience.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection, which evolved into a global pandemic within a short time. Individuals with sickle cell disease (SCD) suffer from underlying cardiopulmonary comorbidities and are at risk of severe complications such as pneumonia, acute chest syndrome, thrombosis, stroke, and multiorgan failure. Whether COVID-19 poses a high risk of morbidity and mortality in SCD patients remains unclear. Patients with SCD and COVID-19 can present with overlapping clinical features such as respiratory symptoms with ground-glass infiltrates, hyperinflammatory state, and increased risk of thromboembolism. This highlights the need to maintain a low threshold for testing for COVID-19 infection among symptomatic and hospitalized SCD patients. We report a case series of nine hospitalized SCD patients diagnosed with COVID-19 from March 18, 2020 to April 30, 2020 at a tertiary medical center in New York City. The mean age of the study population was 27.9 years, and interval since onset of symptoms and hospital presentation was 1-2 weeks. All patients in our series improved and were discharged home. This limited study shows that SCD patients, who are perceived to be high risk, maybe somehow protected from severe symptoms and complications of COVID-19 infection.

Racial and Gender-Based Differences in COVID-19.

The novel coronavirus disease (COVID-19) has become a global health crisis since its first appearance in Wuhan, China. Current epidemiological studies suggest that COVID-19 affects older patients with multiple comorbidities, such as hypertension, obesity, and chronic lung diseases. The differences in the incidence and severity of COVID-19 are likely to be multifaceted, depending on various biological, social, and economical factors. Specifically, the socioeconomic differences and psychological impact of COVID-19 affecting males and females are essential in pandemic mitigation and preparedness. Previous clinical studies have shown that females are less susceptible to acquire viral infections and reduced cytokine production. Female patients have a higher macrophage and neutrophil activity as well as antibody production and response. Furthermore, in-vivo studies of the angiotensin-converting enzyme 2 (ACE2) showed higher expression in the kidneys of male than female patients, which may explain the differences in susceptibility and progression of COVID-19 between male and female patients. However, it remains unknown whether the expression of ACE2 differs in the lungs of male or female patients. Disparities in healthcare access and socioeconomic status between ethnic groups may influence COVID-19 rates. Ethnic groups often have higher levels of medical comorbidities and lower socioeconomic status, which may increase their risk of contracting COVID-19 through weak cell-mediated immunity. In this article, we examine the current literature on the gender and racial differences among COVID-19 patients and further examine the possible biological mechanisms underlying these differences.

Serum Activity of Liver Enzymes Is Associated With Higher Mortality in COVID-19: A Systematic Review and Meta-Analysis.

Background: Abnormal liver chemistries are common findings in patients with COVID-19. It is unclear whether abnormal liver chemistries can predict the severity of COVID-19. Therefore, we compared the serum liver chemistries such as hepatic transaminases, total bilirubin, albumin, and prothrombin time to evaluate whether they can predict severity and mortality in COVID-19. Methods: An electronic search was performed on PubMed/Medline, EMBASE, and Google Scholar for studies comparing liver chemistries in severe and mild COVID-19. The literature search was performed using keywords "COVID-19," "Liver," Aspartate Aminotransferase (AST)," and "Alanine Aminotransferase (ALT)," "AST," and "ALT," in various combinations of "AND/OR" from December 1, 2019, till May 8, 2020. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for each component of liver chemistries. Results: Twenty-two studies were eligible, with 3,256 patients (54.57% males). Seventeen studies compared liver chemistries for severe vs. mild COVID-19, whereas five studies compared liver chemistries in survival vs. non-survival groups. The pooled WMD of AST and ALT in severe vs. mild COVID-19 were 12.23 (95% CI; 8.07, 16.39; p < 0.01) and 8.07 (95% CI 2.55, 11.91; p < 0.01), respectively. The pooled WMD for AST in survivors vs. non-survivors analysis was 8.82 (n = 789; 95% CI; 2.27, 15.37; p < 0.01) and that of ALT was 4.70 (n = 340; 95% CI 0.04,9.35; p = 0.05). Conclusion: Our meta-analysis shows that deranged liver chemistries may indicate severe COVID-19 and could also predict mortality. Larger studies are needed to evaluate the relationship between derangement in liver chemistries and mortality in COVID-19.

COVID-19 extrapulmonary illness - special gastrointestinal and hepatic considerations.

Coronaviruses have caused three global outbreaks in the last 20 years, which include Severe Acute Respiratory Syndrome (SARS) caused by SARS-CoV (SARS-CoV-1), Middle East Respiratory Syndrome (MERS) by MERS-CoV and Coronavirus Disease-2019 (COVID-19) due to SARS-CoV-2. These outbreaks share many similarities, including clinical presentation, transmission, and management. Although respiratory manifestations are responsible for most of the morbidity and mortality in these conditions, extra-pulmonary manifestations such as gastrointestinal symptoms are also increasingly recognized as important symptoms. Important gastrointestinal symptoms include nausea, vomiting, anorexia, diarrhea, and abdominal pain. Hepatic manifestations such as abnormal aminotransferases are also noted in these patients. Early identification of GI symptoms is crucial as some patients can present only with GI manifestations in the absence of pulmonary symptoms. Furthermore, patients with diarrhea have tested positive for viral RNA in the stool. This has been reported even after the resolution of respiratory symptoms and can extend up to many days from the onset of symptoms. Because of this phenomenon, there is a theoretical risk of fecal-oral transmission and the potential spread of the disease. Though GI symptoms are frequently observed, understanding the pathogenesis of these symptoms is crucial, as it can not only of public health importance but could also identify infected patients early in the spread. Understanding the different GI and hepatic manifestations with underlying mechanisms of symptoms can assist in the therapeutic management of these patients. In this article, we summarize various GI and hepatic manifestations with their prevalence, underlying pathophysiology with emphasis on stool positivity.

Increased Serum Aminotransferase Activity and Clinical Outcomes in Coronavirus Disease 2019.

AIM: Elevation of hepatic aminotransferases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) is commonly noted among COVID-19 patients. It is unclear if they can predict the clinical outcomes among hospitalized COVID-19 patients. We aim to assess if elevations in AST/ALT were associated with poor outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively evaluated hospitalized COVID-19 patients with clinically significant elevated aminotransferases (defined as >2 times upper limit of normal) and compared them with COVID-19 patients without an elevation in aminotransferases. RESULTS: The prevalence of elevation in AST/ALT was found to be 13.7% (20/145). The two groups were similar in baseline demographics, comorbidities, and the majority of laboratory tests. There was no difference in the mortality (50% vs. 36.8%, P = 0.32) and median hospital stay (7 days vs. 7 days, P = 0.78). However, there was a statistically significant increase in the rates of mechanical ventilation among elevated aminotransferases group compared with individuals without elevation (50% vs. 24%, P = 0.028). However, this difference was not observed after adjusting for inflammatory markers such as ferritin, lactate dehydrogenase, and lactic acid levels. CONCLUSION: Elevated aminotransferases among hospitalized COVID-19 patients is associated with higher rates of mechanical ventilation but did not achieve statistical significance after controlling for inflammatory markers. Also, patients with elevated aminotransferases did not have higher rates of mortality or prolonged length of stay.