Comprehensive Literature Review and Evidence evaluation of Experimental Treatment in COVID 19 Contagion

Importance: Coronavirus 2019 pandemic (COVID 19) is caused by the Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) virus. The pandemic is affecting the livelihood of millions of people all over the world. At the time of preparing this report, the pandemic has affected 1 827 284 patients, with 113 031 deaths in 185 countries as per Johns Hopkins University. With no proven treatment for the disease, prevention of the disease in the community and healthcare setting is need of the hour. Objective: To perform a comprehensive literature search for preventive measures and experimental treatment options. In this review, we have focused our discussion on the risk of disease transmission, supportive treatment, and possible treatment options based on available evidence. Evidence Review: We performed a literature search on google scholar, PubMed, and society guidelines for literature related to COVID 19 and previous coronavirus pandemics. We included data review articles, observational studies, and controlled trials to synthesize the treatment options for COVID 19. Findings: In this article, we have extensively reviewed and discussed recommendations from various world organizations for the public and healthcare workers. We have also discussed currently available experimental treatments since there is no proven treatment for COVID 19. The best method of dealing with the current outbreak is to reduce the community spread and thus “flatten the curve.” Although Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir, and Azithromycin have been tried, passive immunity through convalescent serum and vaccine is still at an experimental stage. Patients with severe COVID 19 infections could be considered for this experimental treatment through various national randomized control trials, which may eventually lead to an evidence-based treatment strategy. Conclusions and Relevance: Awareness of currently available experimental treatment among healthcare providers and exploration of possible treatment options through evidence is need of the hour. We have discussed the most recently available literature and evidence behind experimental treatment in this article.

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.

Clostridium Difficile and COVID-19: Novel Risk Factors for Acute Portal Vein Thrombosis.

The COVID-19 pandemic has created an unprecedented global health care crisis. COVID-19 patients are found to have increased thrombotic risk. Despite being on prophylactic anticoagulation, many develop serious arterial and venous thromboembolic events. Emerging reports indicate COVID-19 may be considered a novel risk factor for portal vein thrombosis. Although, intra-abdominal infections are identified as risk factors, clostridium difficile colitis has not been typically seen as a risk factor for PVT. We report a case of an elderly female with a recent diagnosis of COVID-19 and no prior history of cirrhosis or malignancy who presented with diarrhea due to clostridium difficile infection. She developed sudden onset severe abdominal pain during the course of hospitalization. Acute portal vein thrombosis was identified on CT imaging of the abdomen, and she improved well with therapeutic anticoagulation. Acute portal vein thrombosis usually results from a combination of local and systemic prothrombotic risk factors. The combination of local infection by clostridium difficile and COVID-19 coagulopathy led to development of portal vein thrombosis in our patient. To the best of our knowledge, this is the first case of portal vein thrombosis reported in a patient with clostridium difficile infection in the setting of COVID-19 coagulopathy. During the current pandemic, clinicians should strongly consider abdominal imaging in patients presenting with abdominal pain due to clostridium difficile infection in the setting of COVID-19 to rule out complications such as portal vein thrombosis. Early diagnosis and treatment of portal vein thrombosis prevent complications of portal hypertension and intestinal infarctions.

Venous Thromboembolism in Hospitalized COVID-19 Patients.

BACKGROUND: Venous thromboembolism (VTE) is increasingly reported in seriously ill patients with COVID-19 infection. Incidence of VTE has been reported before and results varied widely in study cohorts. AREA OF UNCERTAINTY: Incidence of major VTE (segmental pulmonary embolism and above and proximal deep vein thrombosis) which is a contributor to mortality and morbidity is not known. Also, data is unclear on the optimal anticoagulation regimen to prevent VTE. DATA SOURCES: Multiple databases including PubMed were searched until May 12, 2020, to include studies reporting VTE in hospitalized COVID-19 adult patients. MOOSE guidelines were followed in selection, and 11 studies were included. We conducted a systematic review and meta-analysis to quantitatively assess the VTE burden in hospitalized COVID-19 patients and potential benefits of therapeutic dosing of anticoagulation compared with prophylaxis dosing for VTE prevention. THERAPEUTIC ADVANCES: Many societies and experts recommend routine prophylactic anticoagulation with heparin for VTE prevention in hospitalized COVID-19 patients. In this meta-analysis, the pooled rate of major VTE was 12.5% in hospitalized patients and 17.2% in intensive care unit patients. When therapeutic anticoagulation dosing was compared with prophylactic anticoagulation, the pooled odds ratio of VTE was 0.33 (95% confidence interval 0.14-0.75; P = 0.008, I = 0%) suggesting statistical significance with therapeutic dosing of anticoagulation for primary prevention of VTE in all hospitalized patients. However, this should be interpreted with caution as the bleeding events and safety profile could not be ascertained because of lack of adequate information. We recommend applying this finding to hospitalized COVID 19 patients only after carefully weighing individual bleeding risks and benefits. CONCLUSION: Major VTE events, especially pulmonary embolism, seem to be high in COVID-19 patients admitted to the intensive care unit. Therapeutic anticoagulation dosing seems to significantly benefit the odds of preventing any VTE when compared with prophylactic dosing in all hospitalized patients.

Comprehensive Literature Review and Evidence evaluation of Experimental Treatment in COVID 19 Contagion.

IMPORTANCE: Coronavirus 2019 pandemic (COVID 19) is caused by the Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) virus. The pandemic is affecting the livelihood of millions of people all over the world. At the time of preparing this report, the pandemic has affected 1 827 284 patients, with 113 031 deaths in 185 countries as per Johns Hopkins University. With no proven treatment for the disease, prevention of the disease in the community and healthcare setting is need of the hour. OBJECTIVE: To perform a comprehensive literature search for preventive measures and experimental treatment options. In this review, we have focused our discussion on the risk of disease transmission, supportive treatment, and possible treatment options based on available evidence. EVIDENCE REVIEW: We performed a literature search on google scholar, PubMed, and society guidelines for literature related to COVID 19 and previous coronavirus pandemics. We included data review articles, observational studies, and controlled trials to synthesize the treatment options for COVID 19. FINDINGS: In this article, we have extensively reviewed and discussed recommendations from various world organizations for the public and healthcare workers. We have also discussed currently available experimental treatments since there is no proven treatment for COVID 19. The best method of dealing with the current outbreak is to reduce the community spread and thus "flatten the curve." Although Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir, and Azithromycin have been tried, passive immunity through convalescent serum and vaccine is still at an experimental stage. Patients with severe COVID 19 infections could be considered for this experimental treatment through various national randomized control trials, which may eventually lead to an evidence-based treatment strategy. CONCLUSIONS AND RELEVANCE: Awareness of currently available experimental treatment among healthcare providers and exploration of possible treatment options through evidence is need of the hour. We have discussed the most recently available literature and evidence behind experimental treatment in this article.

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.

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.

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.

Clinical Insights into the Gastrointestinal Manifestations of COVID-19.

The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

COVID-19 and gastrointestinal endoscopies: Current insights and emergent strategies.

A new coronavirus emerged in December 2019 in Wuhan city of China, named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the disease was called coronavirus disease-2019 (COVID-19). The infection due to this virus spread exponentially throughout China and then spread across >205 nations, including the United States (US). Gastrointestinal (GI) endoscopies are routinely performed in the US and globally. Previous reports of isolated infection outbreaks were reported with endoscopes acting as potential vectors. While multidrug-resistant organisms have been reported to be spread by endoscopes, few cases of viruses such as hepatitis B and C are noted in the literature. COVID-19 is predominately spread by droplet transmission, although recent evidence has showed that shedding in feces and feco-oral transmission could also be possible. It is unclear if COVID-19 could be transmitted by endoscopes, but it could theoretically happen due to contact with mucous membranes and body fluids. GI endoscopies involve close contact with oral and colonic contents exposing endoscopy staff to respiratory and oropharyngeal secretions. This can increase the risk of contamination and contribute to virus transmission. Given these risks, all major GI societies have called for rescheduling elective non-urgent procedures and perform only emergent or urgent procedures based on the clinical need. Furthermore, pre-screening of all individuals prior to endoscopy is recommended. This article focuses on the risk of COVID-19 transmission by GI shedding, the potential role of endoscopes as a vector of this novel virus, including transmission during endoscopies, and prevention strategies including deferral of elective non-urgent endoscopy procedures.