Gastroenterology and liver disease during COVID-19 and in anticipation of post-COVID-19 era: Current practice and future directions

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.     

COVID-19 Seroprevalence in ED Health Care Professionals Study: A Cross-Sectional Study

IntroductionED health care professionals are at the frontline of evaluation and management of patients with acute, and often undifferentiated, illness. During the initial phase of the SARS-CoV-2 outbreak, there were concerns that ED health care professionals may have been at increased risk of exposure to SARS-CoV-2 due to difficulty in early identification of patients. This study assessed the seroprevalence of SARS-CoV-2 antibodies among ED health care professionals without confirmed history of COVID-19 infection at a quaternary academic medical center.MethodsThis study used a cross-sectional design. An ED health care professional was deemed eligible if they had worked at least 4 shifts in the adult emergency department from April 1, 2020, through May 31, 2020, were asymptomatic on the day of blood draw, and were not known to have had prior documented COVID-19 infection. The study period was December 17, 2020, to January 27, 2021. Eligible participants completed a questionnaire and had a blood sample drawn. Samples were run on the Roche Cobas Elecsys Anti-SARS-CoV-2 antibody assay.ResultsOf 103 health care professionals (16 attending physicians, 4 emergency residents, 16 advanced practice professionals, and 67 full-time emergency nurses), only 3 (2.9%; exact 95% CI, 0.6%-8.3%) were seropositive for SARS-CoV-2 antibodies.DiscussionAt this quaternary academic medical center, among those who volunteered to take an antibody test, there was a low seroprevalence of SARS-CoV-2 antibodies among ED clinicians who were asymptomatic at the time of blood draw and not known to have had prior COVID-19 infection.     

Gastrointestinal insights during the COVID-19 epidemic

Coronavirus disease-2019 (COVID-19) has so far caused hundreds of mortalities worldwide. Although respiratory symptoms are the main complication in COVID-19 patients, the disease is also associated with gastrointestinal problems, with diarrhea, nausea, and vomiting being primary COVID-19 symptoms. Thus, cancer and inflammatory bowel disease (IBD) management, stool viral tests, and virus exposure are major concerns in the context of COVID-19 epidemic. In patients with colorectal cancer and IBD, the colonic mucosa exhibits elevated angiotensin-converting enzyme 2 receptor levels, enhancing COVID-19 susceptibility. In some cases, positive viral stool tests may be the only indicator of infection at admission or after leaving quarantine. Without supplemental stool tests, the risk of undetected COVID-19 transmission is high. Moreover, viral exposure during the regular or emergency endoscopic examination should be avoided. We carefully discuss key gastrointestinal concerns with regard to COVID-19 and call for more attention to such problems.     

Implications of COVID-19 for inflammatory bowel disease: Opportunities and challenges amidst the pandemic

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic various measures have been taken to mitigate the effects of the global health crisis in this unprecedented time. According to the World Health Organization, more than 5 million people have been infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and with more than 300000 deaths attributed to COVID-19 worldwide. There is emerging evidence that SARS-CoV-2 utilizes angiotensin-converting enzyme 2 receptors to enter human cells which are found in abundance in the alveoli and intestines. In addition, the infection is noted to be more severe in patients with co-morbid conditions, those who are malnourished, immunosuppressed and immunocompromised. Inflammatory bowel disease (IBD) which includes ulcerative colitis and Crohn’s disease is chronic remitting and relapsing disorders with intestinal and extraintestinal manifestation. IBD patients are often malnourished and on immunosuppressive medications and there is a hypothetical concern that IBD patients are at substantial risk of COVID-19 infection. The management of IBD patients is often complex and poses unique challenges for gastroenterologists during the pandemic. The purpose of this review article is to summarize the growing level of evidence and understanding of the management of IBD during the COVID-19 pandemic, in the light of international and national gastroenterology society guidelines. We performed a thorough literature search on IBD, SARS-CoV-2 and COVID-19 on PubMed, EMBASE, OVID Medline and Google Scholar and pertaining literature was critically examined and summarized. Per national and international society guidelines and recommendations, IBD is not a risk factor for SARS-CoV-2 infection. IBD patients should continue with their medications and they should follow universal precautions i.e. masks, hand and respiratory hygiene and avoidance of health care facilities and public toilets as general population. Among IBD patients older age, having active disease, and co-morbid conditions are risk factors for a severe SARS-CoV-2 infection. Furthermore, elective endoscopic and surgical procedures can be delayed or deferred until discussing the risks and benefits with patients.     

Convalescent plasma therapy in patients with COVID-19

IntroductionPassive antibody therapy has been used to immunize vulnerable people against infectious agents. In this study, we aim to investigate the efficacy of convalescent plasma (CP) in the treatment of severe and critically ill patients diagnosed with COVID-19.MethodThe data of severe or critically ill COVID-19 patients who received anti-SARS-CoV-2 antibody-containing CP along with the antiviral treatment (n = 888) and an age-gender, comorbidity, and other COVID-19 treatments matched severe or critically ill COVID-19 patients at 1:1 ratio (n = 888) were analyzed retrospectively.ResultsDuration in the intensive care unit (ICU), the rate of mechanical ventilation (MV) support and vasopressor support were lower in CP group compared with the control group (p = 0.001, p = 0.02, p = 0.001, respectively). The case fatality rate (CFR) was 24.7 % in the CP group, and it was 27.7 % in the control group. Administration of CP 20 days after the COVID-19 diagnosis or COVID-19 related symptoms were associated with a higher rate of MV support compared with the first 3 interval groups (≤5 days, 6?10 days, 11?15 days) (p=0.001).ConclusionCP therapy seems to be effective for a better course of COVID-19 in severe and critically ill patients.     

Liver injury in COVID-19: Known and unknown

Since the first report of the coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease is currently continuously evolving. Previous studies have shown varying degrees of liver damage in patients with COVID-19. However, the exact causes of liver injury and the relationship between COVID-19 and liver injury is unclear. This article describes liver injury induced by COVID-19, analyzes its causes, and discusses the treatment and prognosis of liver damage in patients with COVID-19.     

The cardiovascular aspect of COVID-19

The coronavirus disease-2019 (COVID-19), an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2), has hit the world very hard by affecting millions of people across countries hence posing a major health threat on a global scale. This novel virus is thought to enter and cause infection in its host through the attachment of its structural protein known as the S-glycoprotein to angiotensin-converting enzyme 2 (ACE2). Given the rapid spread of COVID-19 with its consequences globally, it is mandatory that health caregivers and researchers across all disciplines abreast themselves with the potential effects that this novel virus may have on their fields and the medical society at large. During the infection, the cardiovascular system is affected by unknown pathomechanistic processes, hence accounting for an increased prevalence of cardiovascular diseases (CVDs) among COVID-19 patients. As cardiovascular researchers, we are more concerned about the cardiovascular aspect of SARS-CoV-2/COVID-19. Hence, this concise review addresses these aspects where CVD as a risk factor of COVID-19, the prevalence of CVDs in COVID-19, and the potential cardiovascular disorders which may evolve owing to COVID-19 are discussed. A better understanding of these issues will be pivotal to improve cardiovascular health during this SARS-CoV-2/COVID-19 pandemic and beyond.     

COVID-19: Gastrointestinal manifestations,liver injury and recommendations

Coronavirus disease 2019 (COVID-19) has caused a pandemic that affected all countries with nearly 270 million patients and 5 million deaths, as of as of December, 2021. The severe acute respiratory syndrome coronavirus 2 virus targets the receptor, angiotensin-converting enzyme 2, which is frequently found in human intestinal epithelial cells, bile duct epithelial cells, and liver cells, and all gastrointestinal system organs are affected by COVID-19 infection. The aim of this study is to review the gastrointestinal manifestations and liver damage of COVID-19 infection and investigate the severe COVID-19 infection risk in patients that have chronic gastrointestinal disease, along with current treatment guidelines. A literature search was conducted on electronic databases of PubMed, Scopus, and Cochran Library, consisting of COVID-19, liver injury, gastrointestinal system findings, and treatment. Liver and intestinal involvements are the most common manifestations. Diarrhea, anorexia, nausea/vomiting, abdominal pain are the most frequent symptoms seen in intestinal involvement. Mild hepatitis occurs with elevated levels of transaminases. Gastrointestinal involvement is associated with long hospital stay, severity of the disease, and intensive care unit necessity. Treatments and follow-up of patients with inflammatory bowel diseases, cirrhosis, hepatocellular carcinoma, or liver transplant have been negatively affected during the pandemic. Patients with cirrhosis, hepatocellular carcinoma, auto-immune diseases, or liver transplantation may have a greater risk for severe COVID-19. Diagnostic or therapeutic procedures should be restricted with specific conditions. Telemedicine should be used in non-urgent periodic patient follow up. COVID-19 treatment should not be delayed in patients at the risk group. COVID-19 vaccination should be prioritized in this group.     

A case of encephalitis following COVID-19 vaccine

We describe the first case of encephalitis following coronavirus disease 2019 (COVID-19) vaccination. Our patient was a 46-year-old Japanese woman who presented with acute onset diplopia. Subsequent magnetic resonance imaging revealed brain stem encephalitis that was rapidly responsive to high dosage steroid therapy and completely improved. Although the occurrence of encephalitis after vaccination could have just been a casual temporal association, her symptoms were temporally correlated with two vaccinations. Our case suggests caution and indicates treatment and prognosis, despite no evidence of a causal relationship. Nonetheless, this report emphasizes the enormous benefits of vaccination, which should not be undermined.     

Role of the extracellular matrix in COVID-19

An outbreak of coronavirus disease 2019 (COVID-19) has spread globally, with over 500 million cases and 6 million deaths to date. COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix (ECM), which is also involved in inflammatory storms. Upon viral infection, ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism, including in the lungs. Additionally, serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets. Consequently, understanding the expression and function of ECM, particularly of the lung, during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression. In this review, we summarize the current findings on ECM, such as hyaluronic acid, matrix metalloproteinases, and collagen, which are linked to the severity and inflammation of COVID-19. Some drugs targeting the extracellular surface have been effective. In the future, these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.     

Promoting access to COVID-19 convalescent plasma in low- and middle-income countries

Low- and middle-income countries (LMICs) remain neglected in the Coronavirus 19 (COVID-19) pandemic. COVID-19 convalescent plasma (CCP) (i.e. plasma collected from individuals after their recovery from COVID-19) has emerged as a leading medical treatment for COVID-19. Studies to date support the safety—and increasingly the efficacy—of CCP to treat COVID-19. This has motivated large-scale procurement and transfusion of CCP, notably in the United States (US), where inventories of CCP have been attained, and government-supported stockpiling of CCP is underway. CCP is a therapy that could be implemented in LMICs. However, systemic and transfusion-specific challenges (e.g. capacity for donor mobilization and collections) impede local procurement of this resource in sufficient volumes to meet clinical demand. This raises the question as to whether there are strategies to facilitate sharing of CCP with LMICs and/or bolstering local capacity for collection to contend with the health crisis. While compelling, there are cost-related, logistical and regulatory barriers to both approaches. For one, there is complexity in diverting national interest (e.g. in the US) away from an epidemic that displays few signs of abating. There are also concerns regarding equitable distribution of CCP in LMICs and how that might be overcome. Further, the barriers to blood donation in general apply to collection of CCP; these obstacles are longstanding, accounting for the inability of many LMICs to meet their blood transfusion needs. Nonetheless, CCP affords dual opportunity for humanitarian outreach while tackling a broader challenge of blood transfusion safety and availability.     

Validation of COVID-19 serologic tests and large scale screening of asymptomatic healthcare workers

ObjectivesSerologic testing for SARS-CoV-2 is an important element in the fight to slow the COVID-19 pandemic. This study aimed to validate two serologic tests for total (IgM, IgG, IgA) SARS-CoV-2 antibodies, (i) the Ortho-Clinical Diagnostics Anti-SARS-CoV-2 Total Antibody assay for the Vitros 5600 analyzers and (ii) a manual laboratory developed ELISA (FDA EUA pending), for use in parallel orthogonal testing of asymptomatic healthcare workers and affiliates of the University of Maryland Medical System.Design and MethodsValidation and verification of the two tests was performed using samples from hospitalized patients that were found to be PCR positive for SARS-CoV-2, samples pre-COVID-19, and samples from individuals with current/previous infections with other viruses. Healthcare workers and affiliates from across the University of Maryland Health System were provided testing free of charge and their results were reported as reactive or non-reactive if the two tests were concordance, or indeterminate if the results were discordant.ResultsValidation testing found the Ortho Vitros test to be 100% (73/73) sensitive, and 99.3% (152/153) specific, while the UMMC ELISA was found to be 97.6% (204/209) sensitive and 100% (288/288) specific. Real world testing among 8399 healthcare workers found that 2.9% (247/8399) of healthcare workers were positive for anti- SARS-CoV-2 antibodies by both tests. An indeterminate rate of 1.1% (91/8399), in which one test reported reactive results, and one as non-reactive was also seen.ConclusionsParallel orthogonal testing improves the positive and negative predictive value of serologic testing in populations with low prevalence. The use of an indeterminate result from parallel orthogonal testing allows for the follow-up and re-testing, which helps resolve discrepancies between assays.     

Efficacy of arbidol in COVID-19 patients: A retrospective study

BACKGROUNDTo date, no treatment has proven to be absolutely effective for coronavirus disease 2019 (COVID-19) patients, and further research is necessary. As a traditional antiviral drug, arbidol was widely used in Wuhan at the beginning of the COVID-19 epidemic and is of increasing interest for treating COVID-19 based on in vitro data suggesting activity against severe acute respiratory syndrome (SARS). Although arbidol has been widely used in China to treat COVID-19 patients, clinical trials to date have not clearly substantiated this approach.AIMTo evaluate the efficacy of arbidol for COVID-19.METHODSA retrospective study was conducted on 132 moderate and severe COVID-19 patients admitted to Jinyintan Hospital and Huoshenshan Hospital (officially designated for COVID-19 treatment) from February to March 2020 in Wuhan, China. This study mainly evaluated the efficacy of arbidol in patients with COVID-19 in the early stage of the SARS coronavirus 2 epidemic. Arbidol was administered at a dose of 200 mg, three times a day, with a 10-d course to adults not receiving any other drugs. Due to the shortage of beds at the time, not every patient could be admitted immediately. We looked for the early stages of the sudden outbreak, places of limited medical resources, limited ward beds, and delayed admission; thus, some patients naturally fit into the control group who did not receive any antiviral drugs. Out of the 132 patients, 72 received arbidol treatment, and 60 did not. We compared the disease course of the two groups and explored the predictors of extended disease duration.RESULTSSeventy-two patients commenced arbidol, and 60 patients did not receive arbidol treatment. The disease duration in the former group was shorter (23.42 ± 6.92 vs 29.60 ± 6.49, P < 0.001). Multivariate regression analysis showed that the risk of a prolonged course of disease increased by 7.158 times in the non-arbidol treatment group. Ferritin > 483.0 ng/mL and lactate dehydrogenase (LDH) > 237.5 U/L were found to be independent risk factors for protracted cases, with the risk of an extended disease duration increasing to 2.852 times and 5.946 times, respectively.CONCLUSIONThe duration course of moderate and severe COVID-19 patients is reduced by 6.183 d when arbidol is administered. Ferritin > 486.5 ng/mL and LDH > 239.5 U/L are independent risk factors for delayed recovery from COVID-19. Early oral administration of arbidol 200 mg t.i.d. with a 10-d course of treatment may be an effective management strategy in COVID-19 patients, particularly those with increased serum ferritin or elevated LDH.     

A retrospective analysis of clinical efficacy of ribavirin in adults hospitalized with severe COVID-19

IntroductionCoronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking.MethodsA total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay.Results68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63–1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay.ConclusionsIn hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.     

Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial

BackgroundEffective treatment for Coronavirus Disease-2019 (COVID-19) is under intensive research. Nigella sativa oil (NSO) is a herbal medicine with antiviral and immunomodulatory activities, and has been recommended for the treatment of COVID-19. This study aimed to evaluate the efficacy of NSO treatment in patients with COVID-19.MethodsAll adult patients with mild COVID-19 symptoms presented to King Abdulaziz University Hospital, Jeddah, Saudi Arabia, were recruited for an open label randomized clinical trial (RCT). They were randomly divided into control or treatment groups, with the latter receiving 500 mg NSO (MARNYS® Cuminmar) twice daily for 10 days. Symptoms were daily monitored via telecommunication. The primary outcome focused on the percentage of patients who recovered (symptom-free for 3 days) within 14-days. The trial was registered at clinicaltrials.gov (NCT04401202).ResultsA total of 173 patients were enrolled for RCT. The average age was 36(±11) years, and 53 % of patients were males. The control and NSO groups included 87 and 86 patients respectively. The percentage of recovered patients in NSO group (54[62 %]) was significantly higher than that in the control group (31[36 %]; p = 0.001). The mean duration to recovery was also shorter for patients receiving NSO (10.7 ± 3.2 days) compared with the control group (12.3 ± 2.8 days); p = 0.001.ConclusionsNSO supplementation was associated with faster recovery of symptoms than usual care alone for patients with mild COVID-19 infection. These potential therapeutic benefits require further exploration with placebo-controlled, double-blinded studies.     

Host-directed therapies: a potential solution to combat COVID-19

ABSTRACT

Coronavirus disease 2019 (COVID-19) characterized by immuno-pathological host responses including pneumonia, lymphopenia, and cytokine storm that leads to severe lung inflammation, developed in acute respiratory distress syndrome (ARDS). In the absence of an effective vaccine or any definitive cure, the use of host-directed therapies is an effective alternative and demanding treatment option in the current pandemic outbreak of COVID-19.