AGA Rapid Recommendations for Gastrointestinal Procedures During the COVID-19 Pandemic

Abstract

In early December 2019, a series of pneumonia cases was reported in Wuhan, China resulting from a novel coronavirus infection designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses as of January 7, 2020, and named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) as of February 11, 2020.1Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (27656) Google Scholar SARS-CoV-2 is a novel enveloped RNA betacoronavirus, that represents the seventh member of the coronavirus family, which includes 4 common human coronaviruses (229E, NL63, OC43, and HKU1) and 2 other strains, including SARS-CoV and Middle East respiratory syndrome–related coronavirus (MERS-CoV).2Lu R. Zhao X. Li J. et al.Genomic characterization and epidemiology of 2019 novel coronavirus: implication for virus origins and receptor binding.Lancet. 2020; 395: 545-574Abstract Full Text Full Text PDF Scopus (6978) Google Scholar,3Zhu N. Zhang D. Wang W. et al.A novel coronavirus from patients with pneumonia in China, 2019.N Engl J Med. 2020; 382: 727-733Crossref PubMed Scopus (15700) Google Scholar SARS-CoV-2 has approximately 79% and 50% phylogenetic similarity to SARS-Co-V and MERS-CoV, respectively.2Lu R. Zhao X. Li J. et al.Genomic characterization and epidemiology of 2019 novel coronavirus: implication for virus origins and receptor binding.Lancet. 2020; 395: 545-574Abstract Full Text Full Text PDF Scopus (6978) Google Scholar This virus is suspected to have a zoonotic origin and is estimated to have resulted in 591,802 cases in 176 countries with 26,996 deaths as of March 27, 2020.4Coronavirus Resource CenterJohns Hopkins University of Medicine.http://coronavirus.jhu.eduDate accessed: March 21, 2020Google Scholar COVID-19 was first reported in the United States on January 20, 2020 and accounted for a total number of 100,717 cases and 1544 deaths as of March 27, 2020.4Coronavirus Resource CenterJohns Hopkins University of Medicine.http://coronavirus.jhu.eduDate accessed: March 21, 2020Google Scholar The morbidity and mortality associated with COVID-19 exceeds previous coronavirus infection outbreaks, including SARS (8098 infections, 774 deaths) and MERS (2458 infections, 848 deaths).5Stadler K. Masignani V. Eickmann M. et al.SARS—beginning to understand a new virus.Nature Rev Microbiol. 2003; 1: 209-218Crossref PubMed Scopus (367) Google Scholar,6Hui D.S. Azhar E.I. Kim Y.J. et al.Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission.Lancet Infect Dis. 2018; 18: e217-e227Abstract Full Text Full Text PDF PubMed Scopus (278) Google Scholar An initial analysis of 72,314 cases from China revealed that an estimated 81% of infections are characterized as mild, 14% are severe, and 5% are critical (defined as respiratory failure, septic shock, and/or multiple organ dysfunction or failure), with an overall fatality rate of 2.3%.7Wu Z, McGoogan JM. Characteristics and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention [published online ahead of print February 24, 2020. JAMA https://doi.org/10.1001/jama.2020.2648.Google Scholar In the United States, an analysis of 4226 cases from the Center for Disease Control and Prevention (CDC) as of March 16, 2020 reported estimated rates of hospitalization of 20.7%–31.4%, intensive care unit admission rates of 4.9%–11.5%, and case fatality rates 1.8%–3.4%.8CDC COVID-19 Response TeamSevere outcomes among patients with coronavirus disease 2019 (COVID-19)–United States, February 12–March 16, 2020.MMWR. 2020; 69: 343-346Crossref PubMed Scopus (1330) Google Scholar The WHO declared a global health emergency on January 30, 20209Mahase E. China coronavirus: WHO declares international emergency as death toll exceeds 200.BMJ. 2020; 368: m408Crossref PubMed Scopus (274) Google Scholar and pandemic status on March 11, 2020.10Bedford J. Enria D. Giesecke J. et al.COVID-19: towards controlling of a pandemic.Lancet. 2020; 395: 1015-1018Abstract Full Text Full Text PDF PubMed Scopus (845) Google Scholar The most common presenting symptoms for COVID-19 include fever, cough, and shortness of breath, although other frequently observed symptoms include fatigue, headache, and muscle soreness. Extrapulmonary symptoms may occur early in the disease course. Gastrointestinal (GI) symptoms, including anorexia, nausea, vomiting, abdominal pain, and/or diarrhea can occur early, but are rarely the sole presenting feature11Pan L. Mu M. Ren H.G. et al.Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional multicenter study.Am J Gastroenterol. 2020; 115: 766-773Crossref PubMed Scopus (1009) Google Scholar; GI symptoms may be associated with poor clinical outcomes, including higher risk of mortality.11Pan L. Mu M. Ren H.G. et al.Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional multicenter study.Am J Gastroenterol. 2020; 115: 766-773Crossref PubMed Scopus (1009) Google Scholar Of note, the first reported case of COVID-19 in the United States presented with a 2-day history of dry cough, fatigue, nausea and vomiting, followed by diarrhea on hospital day 2, with subsequent confirmation of SARS-CoV-2 in a stool specimen.12Holshue M.L. DeBolt C. Lindquist S. et al.First case of 2019 novel coronavirus in the United States.N Engl J Med. 2020; 382: 929-936Crossref PubMed Scopus (3727) Google Scholar Subsequent studies have confirmed positive SARS-CoV-2 cases using real-time reverse transcriptase polymerase chain reaction in stool specimens of patients with COVID-19 infection,13Gu J. Han B. Wang J. COVID-19: gastrointestinal manifestations and potential fecal-oral transmission.Gastroenterology. 2020; 158: 1518-1519Abstract Full Text Full Text PDF PubMed Scopus (899) Google Scholar,14Xiao F. Tang M. Zheng X. et al.Evidence for gastrointestinal infection of SARS-CoV-2.Gastroenterology. 2020; 158: 1831-1833.e3Abstract Full Text Full Text PDF PubMed Scopus (1697) Google Scholar with immunofluorescence data demonstrating that angiotensin converting enzyme II is abundantly expressed in gastric, duodenal, and rectal epithelia, thereby implicating angiotensin converting enzyme II as a potential viral receptor for entry to uninfected host cells, and raising the possibility for fecal–oral transmission, although it is unclear whether the viral concentration in the stool is sufficient for transmission.14Xiao F. Tang M. Zheng X. et al.Evidence for gastrointestinal infection of SARS-CoV-2.Gastroenterology. 2020; 158: 1831-1833.e3Abstract Full Text Full Text PDF PubMed Scopus (1697) Google Scholar Furthermore, angiotensin converting enzyme II receptors may additionally be expressed in hepatic cholangiocytes, potentially permitting direct infection of hepatic cells, and early cohort studies of COVID-19 have revealed that abnormal liver enzymes are commonly observed.15Zhang C. Shi L. Wang F.S. Liver injury in COVID-19: management and challenges.Lancet Gastroenterol Hepatol. 2020; 5: 428-430Abstract Full Text Full Text PDF PubMed Scopus (1124) Google Scholar Multiple questions have been raised regarding the GI and liver manifestations of COVID-19 infection and the implications of SARS-CoV-2 infection on GI endoscopy. A joint society statement by the American Gastroenterological Association (AGA), the American Association for the Study of Liver Diseases, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy on March 15, 2020 highlighted the potential for SARS-CoV-2 transmission through droplets, an established mode of transmission, and possibly fecal shedding, and the associated risk for transmission to endoscopy personnel during GI endoscopy procedures.16American Gastroenterological AssociationJoint GI Society Message: COVID-19 clinical insights for our community of gastroenterologists and gastroenterology care providers.https://www.gastro.org/press-release/joint-gi-society-message-covid-19-clinical-insights-for-our-community-of-gastroenterologists-and-gastroenterology-care-providersDate accessed: March 21, 2020Google Scholar In this document, we seek to summarize the data and provide evidence-based recommendation and clinical guidance. This rapid recommendation document was commissioned and approved by the AGA Governing Board to provide timely, methodologically rigorous guidance on a topic of high clinical importance to AGA members in the context of an emerging pandemic. It was published online on April 1st, 2020 and has an expiration date of six months. This rapid guideline was developed by gastroenterologists and guideline methodologists from the AGA Clinical Guidelines Committee and Clinical Practice Updates Committee, who were assembled on March 15, 2020, in collaboration with the AGA Governing Board, to define time-urgent clinical questions, perform systematic reviews, develop summary evidence profiles, and formulate rapid recommendations. Additionally, to ensure representation of the public/consumer, this guideline was reviewed by 2 COVID-19–positive patients. Panel members disclosed all potential conflicts of interest according to the AGA Institute policy. The target audience of these guidelines includes gastroenterologists, hepatologists, advanced practice providers, nurses, and other health care professionals involved in GI endoscopy. Patients, the public, as well as policy-makers may also benefit from these guidelines. These guidelines are not intended to impose a standard of care for individual institutions, health care systems, or countries. They provide the basis for rational informed decisions for patients, parents, clinicians, and other health care professionals in the setting of a pandemic. This rapid review and guideline was developed using a process described elsewhere.17American Gastroenterological AssociationAGA Institute clinical practice guideline development process.http://www.gastro.org/guidelines-policiesGoogle Scholar Briefly, the AGA process for developing clinical practice guidelines uses the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and best practices as outlined by the National Academy of Medicine (formerly the Institute of Medicine) and Guidelines International Network.18Graham R. Mancher M. Miller et al.Institute of Medicine (US) Committee on Standards for Developing Trustworthy Clinical Practice Guidelines.in: Clinical Practice Guidelines We Can Trust. National Academies Press, Washington, DC2011Crossref Google Scholar With the help of an information specialist, we electronically searched OVID Medline to identify all relevant English studies from inception to March 23, 2020 (including randomized controlled trials, observational studies, and cases series) related to COVID-19 using the newly developed Medical Subject Headings term. Additionally, we looked for indirect evidence related to SARS, MERS, Ebola, and influenza using the systematic review filter. The reference lists of relevant articles were scanned for additional studies. See Supplementary Figure 1 for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram and Supplementary Figure 2 for the search strategy. One reviewer (S.S.) screened titles and abstracts and retrieved relevant articles for each question. A second reviewer (O.A., P.D., J.F., or S.M.S.) confirmed the selected studies and, in certain circumstances, conducted additional Google scholar searches to identify relevant articles. The WHO and CDC websites were also reviewed for relevant articles. Pairs of reviewers extracted the data from the primary studies identified from existing systematic review documents, reviewed the judgments for risk of bias, and conducted specific subgroup analyses using Review Manager software, version 5.3 (The Cochrane Collaboration, Copenhagen, 2014). Evidence profiles were used to display the summary estimates as well as the judgments about the overall certainty of the body of evidence for each clinical question across outcomes. Within the GRADE framework, evidence from randomized controlled trials starts as high-certainty evidence and observational studies start as low-certainty evidence, but can be rated down for the following reasons: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Additionally, evidence from well-conducted observational studies starts as low-certainty evidence but can be rated up for large effects or dose-response. Judgments about the certainty were determined via videoconference discussion to achieve consensus. The certainty of evidence was categorized into 4 levels ranging from very low to high (Table 1). For each question, an overall judgment of certainty of evidence was made based on critical outcomes.Table 1Interpretation of the Certainty in Evidence of Effects Using the Grading of Recommendations Assessment, Development and Evaluation FrameworkCertainty levelDescriptionHighWe are very confident that the true effect lies close to that of the estimate of the effect.ModerateWe are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.LowOur confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.Very LowWe have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect Open table in a new tab During online communications and conference calls, the Guideline Panel developed several recommendations based on the following elements of the GRADE evidence to decision framework: certainty of the evidence, balance of benefits and harms, assumptions about values and preferences, and resource implications. For each guideline statement, the strength of the recommendation and the certainty of evidence to support the recommendation are provided. The phrase “the AGA recommends” is used for strong recommendations, and “the AGA suggests” is used for conditional recommendations (Table 2). The Panel deliberated about the impact of resource limitations on the feasibility and implementation of these recommendations. Therefore, the panel’s main recommendations assume an ideal scenario where there are no resource constraints. However, for settings in which resources require rationing, additional guidance is also provided.Table 2Interpretation of Strong and Conditional RecommendationsaStrong recommendations are indicated by statements that lead with “we recommend” and conditional recommendations are indicated by statements that lead with “we suggest.” Using the Grading of Recommendations Assessment, Development and Evaluation FrameworkImplicationsStrong recommendationConditional recommendationFor patientsMost individuals in this situation would want the recommended course of action and only a small proportion would not.The majority of individuals in this situation would want the suggested course of action, but many would not.For cliniciansMost individuals should receive the intervention. Formal decision aids are not likely to be needed to help individuals make decisions consistent with their values and preferences.Different choices will be appropriate for individual patients consistent with his or her values and preferences. Use shared decision-making. Decision aids may be useful in helping patients make decisions consistent with their individual risks, values, and preferences.For policy-makersThe recommendation can be adapted as policy or performance measure in most situationsPolicy-making will require substantial debate and involvement of various stakeholders. Performance measures should assess whether decision-making is appropriate.a Strong recommendations are indicated by statements that lead with “we recommend” and conditional recommendations are indicated by statements that lead with “we suggest.” Open table in a new tab Low confidence in effect estimates can rarely be tied to strong recommendations. Within the GRADE framework, there are 5 paradigmatic situations in which strong recommendations may be warranted despite low or very low certainty of evidence.19Schünemann H, Brożek J, Guyatt G, et al, eds. GRADE handbook for grading quality of evidence and strength of recommendations. The GRADE Working Group. Available at: guidelinedevelopment.org/handbook. Published October 2013. Accessed March 27, 2020.Google Scholar These situations can be conceptualized as those in which there are clear benefits in the setting of a life-threatening situation, clear catastrophic harms, or equivalence between 2 interventions with clear harms for 1 of the alternatives. The Panel invoked these paradigmatic situations in developing these recommendations. Recommendations in this document may not be valid in the near or immediate future. We will conduct periodic reviews of the literature and monitor the evidence to determine whether recommendations require modification. Based on the rapidly evolving nature of this pandemic, this guideline will likely need to be updated within the next few months. Guan et al20Guan W.J. Ni Z.Y. Hu Y. et al.Clinical characteristics of coronavirus 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (17406) Google Scholar published the largest cohort study to date, which included 1099 hospitalized patients from China with confirmed COVID-19 infection. They reported that 5.0% of COVID-19–infected patients had nausea or vomiting and 3.8% had diarrhea. Across the different published cohort studies, 2.0%–13.8% of patients had diarrhea, 1.0%–10.1% had nausea or vomiting, and 1 study reported the presence of abdominal pain in 2.2% of patients. The cohorts ranged in size from 13 to 191 patients, primarily from Hubei Province, China.1Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (27656) Google Scholar,21Chen N. Zhau M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507Abstract Full Text Full Text PDF PubMed Scopus (12323) Google Scholar, 22Chen L. Liu H.G. Liu W. et al.Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia.Zhonghua Jie He He Hu Xi Za Zhi. 2020; 43: 203-208PubMed Google Scholar, 23Chang D. Lin M. Wei L. et al.Epidemiologic and clinical characteristics of novel coronavirus infections involving 13 patients outside Wuhan, China.JAMA. 2020; 323: 1092-1093Crossref PubMed Scopus (435) Google Scholar, 24Liu K. Fang Y.-Y. Deng Y. et al.Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province.Chin Med J (Engl). 2020; 133: 1025-1031Crossref PubMed Scopus (875) Google Scholar, 25Wang D. Hu B. Hu C. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (13910) Google Scholar, 26Young B.E. Ong S.W.X. Kalimuddin S. et al.Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore.JAMA. 2020; 323: 1488-1494Crossref PubMed Scopus (1331) Google Scholar, 27Zhou F. Ting Yu Ronghui D. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (15960) Google Scholar Most recently, Pan et al11Pan L. Mu M. Ren H.G. et al.Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional multicenter study.Am J Gastroenterol. 2020; 115: 766-773Crossref PubMed Scopus (1009) Google Scholar reported in a cross-sectional study of 204 COVID-19–positive patients from 3 hospitals in Hubei Province, that 29 patients (14.3%) developed diarrhea, 8 patients (3.9%) experienced vomiting, and 4 patients (2.0%) had abdominal pain. A recent meta-analysis of 4243 patients from China suggested that approximately 17.6% of patients had any GI symptom, including 9.2% with pain, 12.5% with diarrhea, and 10.2% with nausea/vomiting.28Cheung K.S. Hung I.F.N. Chan P.P.Y. et al.Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong Cohort: systematic review and meta-analysis.Gastroenterology. 2020; 159: 81-95Abstract Full Text Full Text PDF PubMed Scopus (928) Google Scholar A concern with many of the published studies is the possible duplicate inclusion of the patients across reports, thereby limiting valid performance of pooled estimates in a meta-analysis.29Bauchner H, Golub RM, Zylke J. Editorial concern: possible reporting of the same patients with COVID-19 in different reports [published online ahead of print March 16, 2020]. JAMA https://doi.org/10.1001/jama.2020.3980.Google Scholar There is evidence for the presence of SARS-CoV-2 RNA in stool specimens independent of the presence of diarrhea. Some studies showed that stool continued to be positive for SARS-CoV-2 RNA even after respiratory samples became negative.12Holshue M.L. DeBolt C. Lindquist S. et al.First case of 2019 novel coronavirus in the United States.N Engl J Med. 2020; 382: 929-936Crossref PubMed Scopus (3727) Google Scholar,15Zhang C. Shi L. Wang F.S. Liver injury in COVID-19: management and challenges.Lancet Gastroenterol Hepatol. 2020; 5: 428-430Abstract Full Text Full Text PDF PubMed Scopus (1124) Google Scholar,21Chen N. Zhau M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507Abstract Full Text Full Text PDF PubMed Scopus (12323) Google Scholar,30Wang W. Xu Y. Gao R. et al.Detection of SARS-CoV-2 in different types of clinical specimens.JAMA. 2020; 323: 1843-1844PubMed Google Scholar, 31Yan P. Zhang D. Yang P. et al.Viral load of SARS-CoV-2 in clinical samples.Lancet Infect Dis. 2020; 20: 411-412Abstract Full Text Full Text PDF PubMed Scopus (1019) Google Scholar, 32Chen L. Lou J. Bai Y. COVID-19 disease with positive fecal and negative pharyngeal and sputum viral tests.Am J Gastroenterol. 2020; 115: 790Crossref PubMed Scopus (87) Google Scholar, 33Zhang W. Du R. Li B. et al.Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes.Emerg Microbes Infect. 2020; 9: 386-389Crossref PubMed Scopus (1182) Google Scholar Chen et al32Chen L. Lou J. Bai Y. COVID-19 disease with positive fecal and negative pharyngeal and sputum viral tests.Am J Gastroenterol. 2020; 115: 790Crossref PubMed Scopus (87) Google Scholar reported a case of COVID-19 based on compatible symptoms and lung imaging in a patient with positive stool real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 RNA, but negative pharyngeal swabs and sputum samples. Furthermore, Wang et al30Wang W. Xu Y. Gao R. et al.Detection of SARS-CoV-2 in different types of clinical specimens.JAMA. 2020; 323: 1843-1844PubMed Google Scholar reported confirmation of SARS-CoV-2–positive fecal samples in 2 patients without diarrhea. Liver injury is estimated to occur in up to 20%–30% of patients at the time of diagnosis with SARS-CoV-2 infection.14Xiao F. Tang M. Zheng X. et al.Evidence for gastrointestinal infection of SARS-CoV-2.Gastroenterology. 2020; 158: 1831-1833.e3Abstract Full Text Full Text PDF PubMed Scopus (1697) Google Scholar Severe hepatitis has been reported but liver failure appears to be rare.21Chen N. Zhau M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507Abstract Full Text Full Text PDF PubMed Scopus (12323) Google Scholar The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19, although direct viral infection and drug-induced liver injury cannot be excluded. One study of liver biopsy specimens obtained from a patient with COVID-19 revealed microvesicular steatosis and mild lobular and portal activity suggestive of either SARS-CoV-2 infection or drug-induced liver injury.34Xu Z. Shi L. Wang Y. et al.Pathological finding of COVID-19 associated with respiratory distress syndrome.Lancet Respir Med. 2020; 8: 420-422Abstract Full Text Full Text PDF PubMed Scopus (5483) Google Scholar Abnormal liver enzymes may be observed in both adults and children with COVID-19,35Xia W. Shao J. Guo Y. et al.Clinical and CT features in pediatric patients with COVID-19 infection: different points from adults.Pediatr Pulmonol. 2020; 55: 1169-1174Crossref PubMed Scopus (649) Google Scholar and do not appear to be a major predictor of clinical outcomes.15Zhang C. Shi L. Wang F.S. Liver injury in COVID-19: management and challenges.Lancet Gastroenterol Hepatol. 2020; 5: 428-430Abstract Full Text Full Text PDF PubMed Scopus (1124) Google Scholar Early studies have multiple methodologic limitations, with variable laboratory thresholds, limited longitudinal assessment of liver enzymes, heterogeneous evaluation for alternative etiologies, and limited information regarding baseline liver diseases and confounding variables. Additional studies are needed to further characterize the unique clinical considerations for SARS-CoV-2 infection in patients with chronic liver disease and/or cirrhosis,36Xiao Y. Pan H. She Q. et al.Prevention of SARS-Co-V-2 infection in patients with decompensated cirrhosis.Lancet Gastroenterol Hepatol. 2020; 5: 528-529Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar although preliminary guidance was provided by the American Association for the Study of Liver Diseases on March 23, 2020.37AASLD COVID-19 GuidanceAmerican Association for the Study of Liver Disease.https://www.aasld.org/sites/default/files/2020-03/AASLD-COVID19-ClinicalInsights-FINAL-3.23.2020.pdfDate accessed: March 23, 2020Google Scholar SARS-CoV-2 is presumed to spread primarily via respiratory droplets from talking, coughing, sneezing, and close contact with symptomatic individuals. However human-to-human transmission can occur from unknown infected persons (eg, asymptomatic carriers or individuals with mild symptoms), as well as individuals with virus shedding during the pre-incubation period before symptoms develop.38Cai J. Sun W. Huang J. et al.Indirect virus transmission in cluster of COVID-19 cases, Wenzhou, China, 2020.Emerg Infect Dis. 2020; 26: 1343-1345Crossref PubMed Google Scholar Data related to the spread of SARS-CoV-2 in the early phase of the pandemic have confirmed that health care professionals are at higher risk of infection than the general population. The WHO and Chinese Center for Disease Control and Prevention reported infection of 2055 health care workers as of February 20, 2020 during the index outbreak in Hubei Province, with health care workers facing a rate of infection approximately 3 times that of the general population.39Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19), February 16–24, 2020.https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdfGoogle Scholar This prompted the Chinese Department of Health Reform to deploy more than 40,000 additional health care workers to the region, preserve personal protective equipment (PPE), and implement surveillance measures and quarantine protocols.39Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19), February 16–24, 2020.https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdfGoogle Scholar Such measures appear to have slowed the spread to health care workers, with recent cases primarily attributable to household contacts rather than occupational exposure. Similar trends have been observed in Europe, with an estimated 20% of COVID-19 infections in Italy occurring in health care workers.40Remuzzi A. Remuzzi G. COVID-19 and Italy: what next?.Lancet. 2020; 395: 1225-1228Abstract Full Text Full Text PDF PubMed Scopus (1902) Google Scholar Preliminary reports in the United States also suggest that health care workers are at risk of nosocomial infections, including infection of 20 health care workers among the first 67 COVID-19–positive individuals in Philadelphia, PA, and additional health care workers cases in Washington, New York, and Massachusetts.41COVID-19 testing site opens in South Philadelphia, but with restrictionsABC News Local Philadelphia. March 21, 2020.https://6abc.com/6031085/Google Scholar, 42COVID-19 hits doctors, nurses, EMTs, threatening the health systemWashington Post. March 17, 2020.https://www.washingtonpost.com/health/covid-19-hits-doctors-nurses-emts-threatening-health-system/2020/03/17/f21147e8-67aa-11ea-b313-df458622c2cc_story.htmlGoogle Scholar, 43With 160 employees in quarantine, Berkshire Medical Center taps 54 temporary nursesBerkshire Eagle. March 26, 2020.https://www.berkshireeagle.com/stories/with-160-employees-in-quarantine-bmc-taps-54-temp-nurses,600096?newsletter=600097Google Scholar The spread of disease via health care workers is conce