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      Letter: Precautions for Endoscopic Transnasal Skull Base Surgery During the COVID-19 Pandemic

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          Abstract

          To the Editor: On March 12, 2020 the World Health Organization officially announced the COVID-19 outbreak a pandemic, where to date there have been over 381 000 cases resulting in over 16 500 deaths worldwide. 1 The COVID-19 pandemic is accelerating within the United States, and any information that we can gain from our international colleagues who have already experienced this, or are currently going through it, should be utilized to protect our patients, our hospital teams, and ourselves. The compilation of information below is anecdotal, based primarily on personal communication with international colleagues reporting their individual experiences, and more data is needed before strict policies are set. There is no scientific evidence in this report. However, based on the preliminary observations summarized below and the fast course of events, it would be prudent to exercise an abundance of caution as more data accumulates. Our goal with this preliminary, rapid article is to alert surgeons of the need to temporarily alter their practices to avoid repeating the unfortunate experience of the early period of the epidemic. Personal communication with colleagues deployed in Wuhan, China to combat the COVID-19 outbreak, have warned us about the potential risks of endonasal endoscopic surgery in COVID-19 symptomatic patients. From their reports, a patient with mild flu-like symptoms underwent transphenoidal pituitary surgery in early January 2020, before the severity of this pandemic was well established. Multiple members (>14 by report) of the patient care team, both within and outside of the operating room, became infected from what became recognized as human-to-human transmission of COVID-19. 2 Testing for COVID-19 prior to that time was scarce. A second case of intraoperative transmission of COVID-19 occurred later on January 2020, at the peak of the pandemic in Wuhan province. A young patient with a known pituitary adenoma developed fever and acute vision changes and was diagnosed with pituitary apoplexy and suspected viral pneumonia based on imaging studies. The surgical team was aware of the potential risks of infection, but given the acuity of symptoms proceeded with transphenoidal surgery using personal protective equipment (PPE). The neurosurgeon and 2 operating room (OR) nurses employed N95 masks and the anesthesiologist reportedly used a “home-made” positive pressure helmet. The operation was completed successfully without incident and the surgical team was quarantined after surgery. Within 3 to 4 d, all of them developed fever and respiratory symptoms compatible with pneumonia, except the anesthesiologist. Fortunately, all recovered with no sequelae. The patient, however, required prolonged intubation, but finally recovered. A significant number of doctors who became infected and even died in Wuhan, China were anesthesiologists/critical care doctors, ophthalmologists, and otolaryngologists, possibly due to the high viral shedding from the nasal and oropharyngeal cavity. 3 Health-care providers are at high risk of infection when taking care of COVID-19 patients without PPE. High risk procedures include intubation and procedures involving the upper respiratory tract and gastrointestinal tract with risk for aerosolization, such as endoscopy, bronchoscopy, and laryngoscopy. From our colleagues in Iran, Dr Ebrahim Razmpa, Professor of Otolaryngology at Tehran University Medical Sciences, Dr Saee Atighechi, Associate Professor of Otolaryngology at Yazd University School of Medicine, and Dr Mohammed Hossein Baradanfar, Professor and Chairman of Otolaryngology Yazd University School of Medicine, we have additionally heard that at least 20 otolaryngologists in Iran are currently hospitalized with COVID-19, with 20 more in isolation at home. They are testing only people who have been admitted to the hospital, so those 20 at home are not confirmed, but have classic symptoms. A previously healthy 60-yr old facial plastic surgeon died from COVID-19 3 d ago. A young, otherwise healthy otolaryngology chief resident had a short prodrome, rapidly decompensated and died from what was found to be acute myocarditis and cardiac arrest. It was recently confirmed from these colleagues that he did also test positive for COVID-19. The British Association of Otorhinolaryngology has now also stated 2 of its consultants are on ventilators and being treated for COVID-19. 4 In Athens, 21 staff members of the Athens General Hospital “Hippocrates” are quarantined, as a doctor at the Otolaryngology Clinic reportedly tested positive for COVID-19. 5 Our colleague Dr Puya Deghani-Mobaraki, in Italy, also reports otolaryngologists being affected adversely, but his information is about the possible loss of smell and taste that this virus brings. They are not only seeing it in their patients, but they have noticed it within their own ranks, in otherwise healthy asymptomatic doctors, at rates far above what could be considered normal. This observation has also been reported in the media regarding patients, as an under-reported aspect of this disease process. 6,7 In fact, this symptom has been seen now so commonly in France in association with COVID-19 that the government has issued an official statement instructing citizens with this symptom to contact their physicians, who may advise self-quarantine or to come in and be tested, depending on individual evaluation. 8 Based on this information, and until we know more, we are performing only urgent/emergent surgery at Stanford University at this time. Due to this apparent high risk with endoscopic transnasal surgery on COVID-19 symptomatic patients, despite current limitations in testing capacity, our institution has approved testing for COVID-19 in preoperative patients needing this type of procedure urgently or emergently. This is true even for asymptomatic patients (ie, no cough and/or fever), although the true risk in this cohort of patients is still unknown. If the test is negative and the patient is asymptomatic, we may proceed using normal levels of protective gear; however, the rate of false negative tests is still to be determined, and until this is known, the use of additional levels of PPE, such as N95 and face shields can be considered. If the test is positive, we defer surgery if at all possible until the infection is cleared, verified by repeat testing. When endonasal surgery cannot be postponed in a COVID-19 positive patient, based on guidelines now being used in China, we have recommended to our institutional officials that we utilize full powered air purifying respirator (an enclosed powered system with high efficiency particulate air filter), acknowledging that they have challenging decisions surrounding allocation of limited resources that are urgently needed by our critical care teams taking care COVID-19 patients. 9 Alternatively, a transcranial approach should be considered whenever possible. Because endonasal surgery creates clouds of droplets and aerosols which may permeate the operating environment, anyone in the operating theater requires the same protection when operating on known COVID-19 positives. 10-12 The question of whether 2 separate negative tests are needed before surgery, or if 1 is sufficient, is under active discussion. The test that we are using, developed at Stanford, is an in-house assay that uses a real-time reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2. This first screens for the presence of virus envelope protein, and if positive then evaluates for the presence of the ribonucleic acid (RNA)-dependent RNA polymerase gene for confirmation (Developed by Benjamin Pinsky MD, Stanford University). Positive results from this test have been demonstrated to be very sensitive and very specific and have been given early approval by the Food and Drug Administration. The Chinese center for disease control test uses different gene targets and primers and thus may, or may not, have a different accuracy profile. Conservation of precious testing and PPE resources is another reason to limit these operations to the bare minimum at this time. We also recommend use of as minimal OR team as necessary and that no trainees or observers be allowed in the room both for reasons of safety and to preserve PPE. In the clinic setting, we have similarly restricted visits to only urgent/emergent patients and have ceased the use of spray anesthetic/decongestants, opting instead for nasal pledgets as needed, but preferably avoiding endoscopy whenever possible. We are using N95 masks, face shields, and gowns for all outpatient nasal endoscopies. Please keep in mind that from the time of this submission, the situation may have evolved, and our policies may have changed. We hope that more hard data becomes available soon upon which to base these important decisions. We follow with tempered optimism, the evolution of this pandemic in China, where at this point no new local cases have been reported for several days now, with gradual return to normal surgical activities, including endoscopic endonasal surgery. We thank our international colleagues who have given us this important information, and we extend wishes of safety and health to all our otolaryngology, neurosurgery, and critical care/anesthesia colleagues at this challenging time.

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          Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

          To the Editor: A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic. 1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus. 2 We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans. Our data consisted of 10 experimental conditions involving two viruses (SARS-CoV-2 and SARS-CoV-1) in five environmental conditions (aerosols, plastic, stainless steel, copper, and cardboard). All experimental measurements are reported as means across three replicates. SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours), with a reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per milliliter (Figure 1A). SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard, and viable virus was detected up to 72 hours after application to these surfaces (Figure 1A), although the virus titer was greatly reduced (from 103.7 to 100.6 TCID50 per milliliter of medium after 72 hours on plastic and from 103.7 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). The stability kinetics of SARS-CoV-1 were similar (from 103.4 to 100.7 TCID50 per milliliter after 72 hours on plastic and from 103.6 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). On copper, no viable SARS-CoV-2 was measured after 4 hours and no viable SARS-CoV-1 was measured after 8 hours. On cardboard, no viable SARS-CoV-2 was measured after 24 hours and no viable SARS-CoV-1 was measured after 8 hours (Figure 1A). Both viruses had an exponential decay in virus titer across all experimental conditions, as indicated by a linear decrease in the log10TCID50 per liter of air or milliliter of medium over time (Figure 1B). The half-lives of SARS-CoV-2 and SARS-CoV-1 were similar in aerosols, with median estimates of approximately 1.1 to 1.2 hours and 95% credible intervals of 0.64 to 2.64 for SARS-CoV-2 and 0.78 to 2.43 for SARS-CoV-1 (Figure 1C, and Table S1 in the Supplementary Appendix). The half-lives of the two viruses were also similar on copper. On cardboard, the half-life of SARS-CoV-2 was longer than that of SARS-CoV-1. The longest viability of both viruses was on stainless steel and plastic; the estimated median half-life of SARS-CoV-2 was approximately 5.6 hours on stainless steel and 6.8 hours on plastic (Figure 1C). Estimated differences in the half-lives of the two viruses were small except for those on cardboard (Figure 1C). Individual replicate data were noticeably “noisier” (i.e., there was more variation in the experiment, resulting in a larger standard error) for cardboard than for other surfaces (Fig. S1 through S5), so we advise caution in interpreting this result. We found that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1 under the experimental circumstances tested. This indicates that differences in the epidemiologic characteristics of these viruses probably arise from other factors, including high viral loads in the upper respiratory tract and the potential for persons infected with SARS-CoV-2 to shed and transmit the virus while asymptomatic. 3,4 Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed). These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, 5 and they provide information for pandemic mitigation efforts.
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            SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

            To the Editor: The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, and has been declared a public health emergency of international concern by the World Health Organization, may progress to a pandemic associated with substantial morbidity and mortality. SARS-CoV-2 is genetically related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries in 2002–2003. 1 The epidemic of SARS-CoV was successfully contained through public health interventions, including case detection and isolation. Transmission of SARS-CoV occurred mainly after days of illness 2 and was associated with modest viral loads in the respiratory tract early in the illness, with viral loads peaking approximately 10 days after symptom onset. 3 We monitored SARS-CoV-2 viral loads in upper respiratory specimens obtained from 18 patients (9 men and 9 women; median age, 59 years; range, 26 to 76) in Zhuhai, Guangdong, China, including 4 patients with secondary infections (1 of whom never had symptoms) within two family clusters (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The patient who never had symptoms was a close contact of a patient with a known case and was therefore monitored. A total of 72 nasal swabs (sampled from the mid-turbinate and nasopharynx) (Figure 1A) and 72 throat swabs (Figure 1B) were analyzed, with 1 to 9 sequential samples obtained from each patient. Polyester flock swabs were used for all the patients. From January 7 through January 26, 2020, a total of 14 patients who had recently returned from Wuhan and had fever (≥37.3°C) received a diagnosis of Covid-19 (the illness caused by SARS-CoV-2) by means of reverse-transcriptase–polymerase-chain-reaction assay with primers and probes targeting the N and Orf1b genes of SARS-CoV-2; the assay was developed by the Chinese Center for Disease Control and Prevention. Samples were tested at the Guangdong Provincial Center for Disease Control and Prevention. Thirteen of 14 patients with imported cases had evidence of pneumonia on computed tomography (CT). None of them had visited the Huanan Seafood Wholesale Market in Wuhan within 14 days before symptom onset. Patients E, I, and P required admission to intensive care units, whereas the others had mild-to-moderate illness. Secondary infections were detected in close contacts of Patients E, I, and P. Patient E worked in Wuhan and visited his wife (Patient L), mother (Patient D), and a friend (Patient Z) in Zhuhai on January 17. Symptoms developed in Patients L and D on January 20 and January 22, respectively, with viral RNA detected in their nasal and throat swabs soon after symptom onset. Patient Z reported no clinical symptoms, but his nasal swabs (cycle threshold [Ct] values, 22 to 28) and throat swabs (Ct values, 30 to 32) tested positive on days 7, 10, and 11 after contact. A CT scan of Patient Z that was obtained on February 6 was unremarkable. Patients I and P lived in Wuhan and visited their daughter (Patient H) in Zhuhai on January 11 when their symptoms first developed. Fever developed in Patient H on January 17, with viral RNA detected in nasal and throat swabs on day 1 after symptom onset. We analyzed the viral load in nasal and throat swabs obtained from the 17 symptomatic patients in relation to day of onset of any symptoms (Figure 1C). Higher viral loads (inversely related to Ct value) were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza 4 and appears different from that seen in patients infected with SARS-CoV. 3 The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection 5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV. How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.
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              Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1.

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                Author and article information

                Journal
                Neurosurgery
                Neurosurgery
                neurosurgery
                Neurosurgery
                Oxford University Press
                0148-396X
                1524-4040
                15 April 2020
                15 April 2020
                : nyaa125
                Affiliations
                [1] Departments of Otolaryngology-Head & Neck Surgery and Neurosurgery Stanford University School of Medicine Stanford, California
                Author information
                http://orcid.org/0000-0003-2072-982X
                Article
                nyaa125
                10.1093/neuros/nyaa125
                7184431
                32293678
                080f2355-12d1-4f7a-8540-4dca9f695536
                Copyright © 2020 by the Congress of Neurological Surgeons

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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                AcademicSubjects/MED00930
                Neuros/4
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                covid-19,coronavirus,transmission,endoscopic surgery,extended endoscopic skull base surgery,personal protective equipment (ppe),powered air purifying respirators (papr)

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