Key Words: COVID-19, coronavirus, transmission, endoscopic surgery, extended endoscopic skull base surgery, personal protective equipment (PPE), Powered Air Purifying Respirators (PAPR)

Zara M. Patel, MD; Juan Fernandez-Miranda, MD; Peter H. Hwang, MD; Jayakar V. Nayak, MD, PhD; Robert Dodd, MD, PhD; Hamed Sajjadi, MD; Robert K. Jackler, MD

Stanford University School of Medicine
Departments of Otolaryngology-Head & Neck Surgery and Neurosurgery

On March 12, 2020 the World Health Organization (WHO) officially announced the COVID-19 outbreak a pandemic, where to date there have been over 381,000 cases resulting in over 16,500


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-


deaths worldwide.
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 COVID-19 pandemic is accelerating within the United States, and any

human transmission of COVID-19.
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 two 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 3-4 days, all of them developed fever and respiratory

Testing for COVID-19 prior to that time was scarce. A

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


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 twenty at home are not confirmed, but have classic symptoms. A previously healthy 60 year old facial plastic surgeon died from COVID-19 three days 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 two of its consultants are on


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


quarantine or to come in and be tested, depending on individual evaluation.

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, in spite of current limitations in testing capacity, our institution has approved testing for COVID-19 in pre-operative 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

the high viral shedding from the nasal and oropharyngeal cavity.
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.

Hospital “Hippocrates” are quarantined, as a doctor at the Otolaryngology Clinic reportedly

ventilators and being treated for COVID-19.

In Athens, 21 staff members of the Athens General

tested positive for COVID-19.

aspect of this disease process.
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-


In fact, this symptom has been seen now so commonly in

Healthcare providers are at

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 PAPR (an enclosed powered system with HEPA filter), acknowledging that they have challenging decisions surrounding allocation of limited resources that are urgently needed by our


The question of whether two separate negative tests are needed before surgery, or if one 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 RT-PCR for SARS-CoV-2. This first screens for the presence of virus envelope protein, and if positive then evaluates for the presence of the 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 FDA. The Chinese CDC 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 an 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.

John’s Hopkins Coronovirus Center. Accessed March 21, 2020

2China Newsweek. 329F20A6E839&qimei=bdfe70cd-5bf1-4702-91b7-329f20a6e839

3 doctors-say?fbclid=IwAR2ds9OWRxQuMHAuy5Gb7ltqUGMZNSojVNtFmq3zzcSLb_bO9aGYr7URxaI

critical care teams taking care COVID-19 patients.
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.

Alternatively, a transcranial approach

3van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17. doi: 10.1056/NEJMc2004973. [Epub ahead of print]

55Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020 Mar 19;382(12):1177-1179. doi: 10.1056/NEJMc2001737. Epub 2020 Feb 19.

6Xu K , Lai XQ , Liu Z . Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Feb 2;55(0):E001. doi:

10.3760/cma.j.issn.1673-0860.2020.0001. [Epub ahead of print] [Suggestions for prevention of 2019 novel coronavirus infection in otolaryngology head and neck surgery medical staff].
[Article in Chinese (translated via Google translator); Abstract available in Chinese from the publisher]

7 8 8

9 9 epidemic/30478044.html

10 patients/#48e2a8c85101

11 ile-de-france-controls-reinforc/lang/en

12 Lian, Tingbo (Editor). Handbook of COVID-19 Prevention and Treatment. The First Affiliated Hospital. Zhejiang University School of Medicine. Compiled according to Clinical Experience.

COVID-19 Clinical Practice Guidelines

COVID-19 Clinical Practice Guidelines
Stay current on new guidelines and recommendations.
View Guidelines
New COVID-19 Clinical Guidelines, including the following:
CDC Guidelines for Evaluating and Testing Persons Under Investigation ›
CDC Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons ›
FDA Guidance on Face Masks ›
CMS Guidance for Infection Control and Prevention in Nursing Homes ›
ACC Guidance on Cardiac Implications ›
ISUOG Guidance on COVID-19 During Pregnancy and Puerperium ›
AAO Guidance on COVID-19 for Ophthalmologists ›
CMS Guidance on Containing Hospital Spread of COVID-19 ›
CPAM Rapid Advice Guidelines ›



The 2019 novel coronavirus disease (COVID-19; previously known as 2019-nCoV) outbreak that originated from Wuhan, Hubei province, China, at the end of 2019 was declared a public health emergency of international concern on Jan 30, 2020, by WHO 1).

By early January, terms like “the new coronavirus” and “Wuhan coronavirus” were in common use. On February 11, 2020, a taxonomic designation “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) became the official means to refer to the virus strain, that was previously termed as 2019-nCoV and Wuhan coronavirus. Within a few hours on the same day, the WHO officially renamed the disease as COVID-19.

COVID-19 has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for COVID-19 is not as high (approximately 2-3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organization 2).

COVID-19 and central nervous system

COVID-19 and central nervous system.

Evidence of the Distribution of ACE2 in the Human Brain

The brain has been reported to express ACE2 receptors that have been detected over glial cells and neurons, which makes them a potential target of COVID-19. Previous studies have shown the ability of SARSCoV to cause neuronal death in mice by invading the brain via the nose close to the olfactory epithelium 3).


The complete genome of SARS-CoV-2 from Wuhan, China was submitted on January 17, 2020 in the National Center for Biotechnology 4) (NCBI) database, with ID NC_045512. The genome of SARS-CoV-2 is a 29,903 bp single-stranded RNA (ss-RNA) coronavirus. It has now been shown that the virus causing COVID-19 is a SARS-like coronavirus that had previously been reported in bats in China.


In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of disease. Zhang et al. conducted an online search for all treatment options related to coronavirus infections as well as some RNA-virus infection and found that general treatments, coronavirus-specific treatments, and antiviral treatments should be useful in fighting COVID-19. They suggested that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children’s RNA-virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, convalescent plasma should be given to COVID-19 patients if it is available. In conclusion, they suggested that all the potential interventions be implemented to control the emerging COVID-19 if the infection is uncontrollable. 5).

A statement by the Ministry of Science and Technology of China encouraged researchers to focus their efforts on epidemic prevention and to publish their results in Chinese.

The emphasis on publishing clinical research in English helps to facilitate knowledge exchange between Chinese scientists and the rest of the world. They hope the research community will make efforts to disseminate all findings relevant to the outbreak of COVID-19 in Chinese in addition to English publishing outlets. For example, clinical research papers about COVID-19 and SARS-CoV-2 in any Lancet journal were translated into Chinese, and these translated Articles were provided rapidly to the public in China free of charge. Broad dissemination in both Chinese and English will accomplish the goals of communicating timely and crucial findings to the international scientific community, while also disseminating this information to health-care workers on the frontline who need to understand the epidemiological and clinical features of COVID-19. This strategy will improve effective control strategies to ultimately contain the virus and protect the health of the public 6).


Diabetes is a risk factor for the progression and prognosis of COVID-19

A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well we treatment measures were collected and analyzed.

Guo et al. found that COVID-19 patients without other comorbidities but with diabetes (n=24) were at higher risk of severe pneumonia, the release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin, and coagulation index, D-dimer, were significantly higher (p< 0.01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19.

Data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration 7).

Operating room preparation for COVID-19

see Operating room preparation for COVID-19.

Lombardy region

The following clinical situations have been defined as neurosurgical emergencies

Cerebral hemorrhages (subarachnoid and intraparenchymal)

Acute hydrocephalus

Tumors at risk of intracranial hypertension

Spinal cord compressions with neurological deficit or at risk of

Traumatic cranial and spinal trauma emergencies 8).

Emotional impact

The emotional impact of COVID-19: from medical staff to common people was published by Montemurro from the Department of Neurosurgery, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy;



WHO. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). Jan 30, 2020. (2019-ncov) (accessed Feb 1, 2020).

Palacios Cruz M, Santos E, Velázquez Cervantes MA, León Juárez M. COVID-19, a worldwide public health emergency. Rev Clin Esp. 2020 Mar 20. pii: S0014-2565(20)30092-8. doi: 10.1016/j.rce.2020.03.001. [Epub ahead of print] Review. English, Spanish. PubMed PMID: 32204922.

Netland, J., Meyerholz, D. K., Moore, S., Cassell, M., and Perlman, S. (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol. 82 (15), 7264−75.

Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome. Nucleotide, National Center for Biotechnology Information (NCBI), National Library of Medicine (US), National Center for Biotechnology Information, Bethesda, MD, https://www. (accessed on 2020-02-28).

Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020 May;92(5):479-490. doi: 10.1002/jmv.25707. Epub 2020 Mar 3. Review. PubMed PMID: 32052466.

Xiang YT, Li W, Zhang Q, Jin Y, Rao WW, Zeng LN, Lok GKI, Chow IHI, Cheung T, Hall BJ. Timely research papers about COVID-19 in China. Lancet. 2020 Feb 29;395(10225):684-685. doi: 10.1016/S0140-6736(20)30375-5. Epub 2020 Feb 17. PubMed PMID: 32078803.

Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, Qin R, Wang H, Shen Y, Du K, Zhao L, Fan H, Luo S, Hu D. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 Mar 31:e3319. doi: 10.1002/dmrr.3319. [Epub ahead of print] PubMed PMID: 32233013.

Zoia C, Bongetta D, Veiceschi P, Cenzato M, Di Meco F, Locatelli D, Boeris D, Fontanella MM. Neurosurgery during the COVID-19 pandemic: update from Lombardy, northern Italy. Acta Neurochir (Wien). 2020 Mar 28. doi: 10.1007/s00701-020-04305-w. [Epub ahead of print] PubMed PMID: 32222820.

COVID-19 is an emerging, rapidly evolving situation.

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