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Show moreBackground & aims: Multiple gastrointestinal (GI) symptoms, including diarrhea, nausea/vomiting, and abdominal pain, as well as liver enzyme abnormalities, have been variably reported in patients with coronavirus disease 2019 (COVID-19). This document provides best practice statements and recommendations for consultative management based on a systematic review and meta-analysis of international data on GI and liver manifestations of COVID-19. Methods: We performed a systematic literature search to identify published and unpublished studies using OVID Medline and preprint servers (medRxiv, LitCovid, and SSRN) up until April 5, 2020; major journal sites were monitored for US publications until April 19, 2020. We pooled the prevalence of diarrhea, nausea, vomiting, and abdominal pain, as well as liver function tests abnormalities, using a fixed-effect model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Results: We identified 118 studies and used a hierarchal study selection process to identify unique cohorts. We performed a meta-analysis of 47 studies including 10,890 unique patients. Pooled prevalence estimates of GI symptoms were as follows: diarrhea 7.7% (95% confidence interval [CI], 7.2%-8.2%), nausea/vomiting 7.8% (95% CI, 7.1%-8.5%), and abdominal pain 2.7% (95% CI, 2.0%-3.4%). Most studies reported on hospitalized patients. The pooled prevalence estimates of elevated liver abnormalities were as follows: aspartate transaminase 15.0% (95% CI, 13.6%-16.5%) and alanine transaminase 15.0% (95% CI, 13.6%-16.4%). When we compared studies from China to studies from other countries in subgroup analyses, diarrhea, nausea/vomiting, and liver abnormalities were more prevalent outside of China, with diarrhea reported in 18.3% (95% CI, 16.6%-20.1%). Isolated GI symptoms were reported rarely. We also summarized the Gl and liver adverse effects of the most commonly utilized medications for COVID-19. Conclusions: GI symptoms are associated with COVID-19 in <10% of patients. In studies outside of China, estimates are higher. Further studies are needed with standardized GI symptoms questionnaires and liver function test checks on admission to better quantify and qualify the association of these symptoms with COVID-19. Based on findings from our meta-analysis, we provide several Best Practice Statements for the consultative management of COVID-19. Keywords: COVID-19; Gastrointestinal and Liver Manifestations.
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Show moreDigestive manifestations appear to be common in patients with coronavirus disease 2019 (COVID19). Gastroenterologists will invariably come into contact with infected patients, and the risk of intraprocedural exposure is well established. Recommendations have been issued to guide personal protective equipment (PPE) use and the triage of procedural urgency, among other operational considerations. In response, institutions providing gastroenterology and endoscopy services have taken urgent action to protect patients and staff, but the uptake and extent of these practice changes in North America is unknown. We conducted a survey of gastroenterology and endoscopy practices to assess the response to the COVID-19 pandemic across the continent.
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Show moreThe etiological agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus SARS-CoV. Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies. To begin to understand its biochemical and immunological properties, we expressed both full-length and ectodomain of the protein in various primate cells. Our results show that the protein has an electrophoretic mobility of about 160–170 kDa. The protein is glycosylated with high mannose and/or hybrid oligosaccharides, which account for approximately 30 kDa of the apparent protein mass. The detection of S-protein by immunoassays was difficult using human convalescent sera, suggesting that the protein may not elicit strong humoral immune response in virus-infected patients. We were able to pseudotype murine leukemia virus particles with S-protein and produce SARS pseudoviruses. Pseudoviruses infected Vero E6 cells in a pH-independent manner and the infection could be specifically inhibited by convalescent sera. Consistent with low levels of antibodies against S-protein, neutralizing activity was weak with 50% neutralization titers ranging between 1:15 to 1:25. To facilitate quantifying pseudovirus-infected cells, which are stained blue with X-Gal, we devised an automated procedure using an ELISPOT analyzer. The high-throughput capacity of this procedure and the safety of using SARS pseudoviruses should make possible large-scale analyses of neutralizing antibody responses against SARS-CoV.
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Show moreSevere acute respiratory syndrome (SARS) is caused by a novel coronavirus, SARS-CoV. Virus entry into cells is mediated through interactions between spike (S) glycoprotein and angiotensin-converting enzyme 2 (ACE2). Alanine scanning mutagenesis analysis was performed to identify determinants on ACE2 critical for SARS-CoV infection. Results indicated that charged amino acids between residues 22 and 57 were important, K26 and D30, in particular. Peptides representing various regions of ACE2 critical for virus infection were chemically synthesized and evaluated for antiviral activity. Two peptides (a.a. 22–44 and 22–57) exhibited a modest antiviral activity with IC(50) of about 50 μM and 6 μM, respectively. One peptide comprised of two discontinuous segments of ACE2 (a.a. 22–44 and 351–357) artificially linked together by glycine, exhibited a potent antiviral activity with IC(50) of about 0.1 μM. This novel peptide is a promising candidate as a therapeutic agent against this deadly emerging pathogen.
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Show moreIn this review, we summarize the current status of nucleic acid and antigen testing required for diagnosing SARS-CoV-2 infection and COVID-19 disease. Nucleic acid amplification (NAAT) and antigen-detection (Ag) tests occupy a critically important frontline of defense against SARS-CoV-2 in clinical and public health settings. In early stages of this outbreak, we observed that identifying the causative agent of a new illness of unknown origin was greatly accelerated by characterizing the nucleic acid signature of the novel coronavirus. Results from nucleic acid sequencing led to the development of highly sensitive RT-PCR testing for use in clinical settings and to informing best practices for patient care, and in public health settings to the development of strategies for protecting populations. As the current COVID-19 pandemic has evolved, we have seen how NAAT performance has been used to guide and optimize specimen collection, inform patient triage decisions, reveal unexpected clinical symptoms, clarify risks of transmission within patient care facilities, and guide appropriate treatment strategies. For public health settings during the earliest stages of the pandemic, NAATs served as the only tool available for studying the epidemiology of this new disease by identifying infected individuals, studying transmission patterns, modeling population impacts, and enabling disease control organizations and governments to make challenging disease mitigation recommendations to protect the expanding breadth of populations at risk. With time, the nucleic acid signature has provided the information necessary to understand SARS-CoV-2 protein expression for further development of antigen-based point-of-care (POC) diagnostic tests. The advent of massive parallel sequencing (ie, next generation sequencing) has afforded the characterization of this novel pathogen, informed the sequences best adapted for RT-PCR assays, guided vaccine production, and is currently used for tracking and monitoring SARS-CoV-2 variants.
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Show moreIn response to the COVID-19 pandemic, US federal and state governments have implemented wide-ranging stay-at-home recommendations as a means to reduce spread of infection. As a consequence, many US healthcare systems and practices have curtailed ambulatory clinic visits—pillars of care for patients with heart failure (HF). In this context, synchronous audio/video interactions, also known as virtual visits (VVs), have emerged as an innovative and necessary alternative. This scientific statement outlines the benefits and challenges of VVs, enumerates changes in policy and reimbursement that have increased the feasibility of VVs during the COVID-19 era, describes platforms and models of care for VVs, and provides a vision for the future of VVs.
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Show moreBackground and study aims: There is a consensus among gastroenterology organizations that elective endoscopic procedures should be deferred during the COVID-19 pandemic. While the decision to perform urgent procedures and to defer entirely elective procedures is mostly evident, there is a wide “middle ground” of time-sensitive but not technically urgent or emergent endoscopic interventions. We aimed to survey gastroenterologists worldwide using Twitter to help elucidate these definitions using commonly encountered clinical scenarios during the COVID-19 pandemic. Methods: A 16-question survey was designed by the authors to include common clinical scenarios that do not have clear guidelines regarding the timing or urgency of endoscopic evaluation. This survey was posted on Twitter. The survey remained open to polling for 48 hours. During this time, multiple gastroenterologists and fellows with prominent social media presence were tagged to disseminate the survey. Results: The initial tweet had 38,795 impressions with a total of 2855 engagements. There was significant variation in responses from gastroenterologists regarding timing of endoscopy in these semi-urgent scenarios. There were only three of 16 scenarios for which more than 70 % of gastroenterologists agreed on procedure-timing. For example, significant variation was noted in regard to timing of upper endoscopy in patients with melena, with 44.5 % of respondents believing that everyone with melena should undergo endoscopic evaluation at this time. Similarly, about 35 % of respondents thought that endoscopic retrograde cholangiopancreatography should only be performed in patients with choledocholithiasis with abdominal pain or jaundice. Conclusion: Our analysis shows that there is currently lack of consensus among gastroenterologists in regards to timing of semi-urgent or non-life-threatening procedures during the COVID-19 pandemic. These results support the need for the ongoing development of societal guidance for these “semi-urgent” scenarios to help gastroenterologists in making difficult triage decisions.
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