key: cord-0833031-o6txiory authors: Perisetti, Abhilash; Gajendran, Mahesh; Boregowda, Umesha; Bansal, Pardeep; Goyal, Hemant title: COVID‐19 and gastrointestinal endoscopies: current insights and emergent strategies date: 2020-04-13 journal: Dig Endosc DOI: 10.1111/den.13693 sha: 476c23e50537ff8bce08fca1ba9c5ebfc8edde94 doc_id: 833031 cord_uid: o6txiory 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 disease was called as 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 predominately spread by droplet transmission, although recent evidence 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 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. Coronaviruses are a group of medium-sized positive-sense single-stranded RNA viruses with crownlike structure due to projections (S protein projections) noted over the surface of the virus. 1 There are four genera (α, β, γ, δ) of coronaviruses. Of these, α genera (229 E, NL63) and β genera (HKU1, OC43, MERS, SARS-CoV) affect humans. 2 (Figure) . 7 However, the origin of the novel SARS-CoV-2 is unclear so far. The structure of this virus is similar to one reported in bats and SARS1CoV-1. Reports This article is protected by copyright. All rights reserved indicate that this virus first affected in the Hubei Province of China in individuals exposed to seafood market. This market traded live animals as well. While the intermediary hosts for SARS-CoV-2 are unclear, Pangolins and snakes are suspected. 8 Though the epicenter of this pandemic was in Wuhan of Hubei province of China, it soon spread to various other countries quickly ( Figure 2 ). 9 Now, the primary source of the spread of the virus is in Europe, possibly because of tourism. Initially, the virus was thought to spread from bats via an unknown intermediary to humans, but a human to human spread has become rampant, leading to an exponential increase in the number of cases. 10 Cases continue to rise with a significant number in Japan, South Korea, the United Kingdom, and the rest of the world. COVID-19 has affected more than 135 countries, and this number is only expected to rise. 10 The exact number of cases is unknown but likely underrepresented due to a delay in the diagnosis, lack of availability of testing kits, and minor symptoms in 80% of cases. Furthermore, in China, the definition of a positive case has been defined as any patient with clinical, radiological, and epidemiological features of COVID-19 rather than based on positive nucleic acid testing. 11 This makes it a formidable task to assess the exact number of cases in China. Doubling time of SARS-CoV-2 has been reported as 1.8 days, which is likely to change as human to human transmission rises. 12 The incubation period of the virus is 2-14 days, with a median period of 5 days. The infection transmission occurs from virus droplets by either symptomatic or asymptomatic individuals, and it can remain viable for 2-3 days on plastic and metallic surfaces. The transmission occurs with the contact of these droplets with mucous membranes (nose, mouth, and eyes). However, reports of infection transmission with contaminated water, stools, with subsequent fecooral route have also been reported. Data on the presence of SARS-CoV-2 in stool specimens are sparse. As it is predominately a respiratory pathogen, most of the data is restricted to nasopharyngeal testing. However, few reports of stool testing are noted. 13 Viral shedding in stools is reported both in symptomatic and This article is protected by copyright. All rights reserved asymptomatic patients. For example, the virus was present in stools samples at day 17 in the asymptomatic individuals with prior exposure. This positivity was again noted for an additional nine days. 14 Stool specimen positive rate was identified as high as 29%. 15 This concept is critical in understanding the transmission of COVID-19 as human to human transmission, which could occur between asymptomatic individuals not only from respiratory droplets but potentially from stool specimens too. 16 these surfaces for hours to days. 5 Intestinal tropism is noted with SARS-CoV-1 and could be one of the mechanisms of the gastrointestinal manifestations of diarrhea. Active viral replication was noted in both small and large intestine biopsies obtained via colonoscopy, which could last for more than ten weeks after the onset of symptoms. 18 Multiple outbreaks were reported of this virus among healthcare workers, including physicians, nurses, and healthcare assistants. 19 These findings of stool or sewage as a potential source of viral shedding and transmission among previous corona viral pandemics and the current finding of positive stools specimens among asymptomatic COVID-19 patients raises concern. Further studies are needed to know if stool samples could be utilized as a screening tool for identification of asymptomatic carriers. Fomites (inanimate objects) are important and have the potential for carrying coronavirus and could play a role in the transmission. MERS-CoV demonstrated high affinity and survival ex-vivo and retained its infectivity for up to 60 minutes after aerosolization. 7 Similarly, SARS-CoV-2 survival has been reported on confined public spaces such as restrooms, elevators, and doorknobs, etc. 20 In general, human coronaviruses can remain infectious on fomites for up to 9 days at room temperature (based on the data from 229 E coronavirus). 21 21 This duration also increases with a higher inoculum of the virus and higher humidity (50% compared to 30%). 22 During active shedding of the virus, any This article is protected by copyright. All rights reserved non-living object could be contaminated by infected respiratory droplets, which could be transmitted to other individuals. Endoscopes come in direct contact with body fluids and oralpharyngeal mucosa, which can contaminate them, especially during active viral shedding. Though the transmissibility of coronaviruses from fomites to hands is unknown, data has been extrapolated from experience with other viruses such as influenza A and parainfluenza. Fomite transmission with influenza A is 31.6% to the hands compared to about 1.5% with parainfluenza 3. 23, 24 While no reports of viral culture of endoscopic surface or tip have been reported and possibility of transmission is yet to be researched. Gastrointestinal endoscopy suites are a conglomeration of endoscopists, nursing staff, technicians, anesthesia providers, and multiple types of equipment. Due to multiple procedures performed every day involving getting the luminal access at a close distance such as the oral cavity, esophagogastroduodenoscopy, biliary, and colorectum, endoscopy staff gets exposed to plentiful respiratory and oropharyngeal microbial flora. In 2002-2003 SARS-CoV-1 pandemic, 21% of individuals affected were healthcare workers. 25 Furthermore, aggressive suctioning, multiple exchanges of catheters via endoscope working channels during these procedure increases the splash rates, which puts the endoscopy personnel at risk. 26 Studies have shown an increased exposure of microorganisms to endoscopists' face, eyes, and skin. 27 Besides, the contamination has also been observed on endoscopy suite walls and post-op areas. 28 Some of the procedures can induce coughing (such as EGD) and increase the spread of aerosolized respiratory droplets. In most cases, these splashes are not recognized by the endoscopists. This can put the entire endoscopy suite and staff at risk of transmission since SARS-CoV-1, and potentially SARS-CoV-2 spread has been estimated to up to 6 feet from the infected individuals via droplets. 29 This article is protected by copyright. All rights reserved Contaminated flexible endoscopes have been reported as the vector for transmission of infections for many years. 31 The exact number of infections though unclear, are likely underreported, possibly due to asymptomatic infections, incomplete surveillance, and prolonged latency. Healthcareassociated infection outbreaks have been reported in the past, forcing FDA and CDC to recommend comprehensive endoscope cleaning strategies with high-level disinfection and reprocessing. 32 Infections related to the duodenoscopes and echoendoscopes are more frequent than colonoscopes and esophagogastroduodenoscopy (EGD) scopes. While most of these infections occur due to multidrug resistance organisms (MDRO), the transmission of other microbial organisms have also been reported. 33 The sophisticated design of the elevator channel of duodenoscopes can harbor microorganisms and might be challenging to disinfect. 34 Microbials form a biofilm with a matrix around these endoscopes, which might protect them from drying and penetration of disinfectants. 35 Historically, salmonellae were the most commonly reported organisms from 1974 to 1988. Gradually this trend was replaced by other virulent organisms such as Pseudomonas aeruginosa and carbapenem-resistant organisms. 36 Infrequently, viral transmission through endoscopes has been reported, especially with Hepatitis B and Hepatitis C viruses. 37 Hepatitis B transmission occurred after endoscopy with an instrument used in HBV-positive patient and immediately after gastroscopy. 38, 39 Hepatitis C has been shown to be transmitted by infected scopes. Enteroviruses and HIV can also be theoretically transmitted via endoscopes. 40 Artificially contaminated endoscopes with enteroviruses were disinfectants such as glutaraldehyde. 41 Similarly, infectious agents such as prions (proteins without nucleic acid) can be transmitted by the GI tract (given accumulation in the lymphoid tissue), although rare. 42 Though COVID-19 is predominately spread by respiratory droplets, the virus is also present in This article is protected by copyright. All rights reserved affected by gut flora, this could pose a risk not only to the endoscopists, nurses, and other endoscopy staff but also could be a vector for potential transmission to other patients. 31 While no cases of endoscope-related COVID-19 transmission has been reported so far, this risk exists, especially with previous experiences with Hepatitis B and C viruses. It is reassuring that post-cleaning samples of SARS-CoV-2 became negative, indicating that current endoscope disinfection techniques are sufficient. 21 Screening colonoscopy is one of the most common procedures performed in the endoscopy suite on a daily basis. 43 Most of these patients are 50 years or older. This unique subset of patients (often with comorbidities) is at the highest risk due to their increased susceptibility to SARS-CoV-2. 10 Elderly individuals with pre-existing conditions are at the highest risk of developing severe disease and mortality. The fatality rate of 4-11% was observed in adults, but it can be as high as 50-75% in the elderly population with the overall fatality of 2-3%. 44 As stated earlier, the disease symptoms can vary from asymptomatic or minimal symptoms to severe disease with multiorgan dysfunction and death. About 80% of the individuals have a milder form of sickness, and 20% develop severe disease. This can make these asymptomatic patients go unnoticed during the pre-operative, endoscopy suites, and post-operative area with increased risk of transmission of disease. 45 Because of these risks, there is a need to call for increased vigilance and careful screening of individuals who are at risk and deferring their procedures until this pandemic is over, especially if they are elective nonurgent in nature. The standard face shield might be ineffective in blocking small viral particle and hence a respirator (N95) is recommended to filter airborne particles. Safe distancing of accompanying personnel including caregivers and relatives, is recommended as well. 49 Disinfection of the endoscopy equipment should be performed as they can potentially become vectors. Strict implementation of Accepted Article guidelines on the infection control in the endoscopy unit is strongly recommended. 41, 52 If possible, procedures should be performed in negative-pressure rooms to minimize transmission. 52 Pre-screening of patients undergoing elective endoscopy has been suggested by ASGE. Patients are classified into low, intermediate, or high-risk based on their history (contact with an individual with positive SARS-COV-2, visitation to highest or high-risk country), symptoms (fever, shortness of breath, cough, diarrhea). 49 While these actions minimize the risk of individuals undergoing endoscopy, the success rate in preventing transmission is unknown. Until more data is available, these recommendations should be used at the full extent to minimize the transmission risk. Besides, evaluation of endoscopy staff for clinical symptoms and exposure history is paramount to decrease the spread from staff to patients and among staff. Some of the characteristics of COVID-19, which make the transmission prevention challenging include -asymptomatic individuals could shed the virus, onset of transmission before the start of symptoms, relatively non-specific symptoms, and ongoing shedding after the resolution of symptoms. 53 If staff develops symptoms of fever and upper respiratory infection, or exposure to a positive case, the local healthcare safety protocols should be followed while keeping them off work. Currently, all contacts are being closely monitored for the development of symptoms of COVID-19. 50 Coronaviruses can persist on different types of fomites, including steel, aluminum, wood, paper, glass, plastic, silicon rubber, disposable gown, and ceramic. Viral presence and duration are dependent on the size of inoculum, temperature, and type of strain. 21 Multiple biocidal agents such as ethanol, 2-propanol, sodium hypochlorite, glutaraldehyde, povidone-iodine, and hydrogen peroxide have been used for disinfection. 54 Ethanol (62%-71% concentration), 2% glutaraldehyde, This article is protected by copyright. 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