Letter: The Risk of COVID-19 Infection During Neurosurgical Procedures: A Review of Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) Modes of Transmission and Proposed Neurosurgery-Specific Measures for Mitigation

Abstract

To the Editor: The novel coronavirus disease of 2019 (COVID-19) is a disease caused by the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). It was first reported in December 2019 as a series of cases of pneumonia with an unknown etiology clustered around a food market in Wuhan City, China.1 The infection spread quickly and was declared a pandemic by the World Health Organization (WHO) on March 11, 2019.2 By March 30, more than 782 365 confirmed cases were reported and a third of the world population were living in confinement to try to contain the virus.3 While the disease itself is often mild, approximately 11% of cases require acute medical care, and this cohort quickly overwhelmed healthcare systems around the world.4 In anticipation of such a demand, hospitals in many countries quickly stopped all nonurgent visits, procedures, and surgeries, freeing up beds, equipment, and workforce.5 While neurosurgeons are not on the frontline of COVID-19 management and treatment, they commonly care for critically ill patients who will continue to present with subarachnoid hemorrhages, subdural hematomas, brain tumors, traumatic brain injuries, spinal cord injuries, and compressive myelopathies while the pandemic occurs. While public health measures such as quarantine and social distancing are proving effective at slowing the spread,6,7 surgeons remain in direct contact with their patients throughout their operations. Protecting the surgical team from contracting COVID-19 is of utmost importance as they are both a potential vector for patient contamination and a scarce resource that cannot be easily replaced. The goal of this paper is to briefly review how SARS-CoV-2 is transmitted and propose measures that could be implemented to minimize the risk of contaminating the operating room (OR) personnel during the most common neurosurgical procedures. Methods and ethical considerations are discussed in the Supplemental Digital Content. SARS-CoV-2 TRANSMISSION Sites of Entry Phylogenetic analysis revealed that the SARS-CoV-2 virus probably evolved from the bat SARS-like CoV (bat-SL-CoVZC45, MG772933.1) virus.1,8,9 It falls into the genus β-coronavirus, which includes SARS-CoV (80% sequence homology) and Middle East respiratory syndrome coronavirus (MERS-CoV), both responsible for previous outbreaks in 2003 and 2012, respectively. Human-to-human transmission was well documented early on and contributed to the rapid spread of the disease.9,10 The virus has been shown to exploit the angiotensin-converting enzyme 2 (ACE2) as a receptor for cell entry, as was the case for SARS-CoV, but unlike MERS-CoV.8,11-13 ACE2 is expressed in the human airway epithelium, lung parenchyma, vascular endothelium, kidney cells, small intestine cells, and, to a lesser extent, central nervous system (CNS) cells.14,15 This pattern of expression therefore supports the respiratory and gastrointestinal tracts as the primary sites of entry. Biodistribution Once infected, individuals can show varying tissue responses and virus biodistribution. In a study of 1070 specimens from 205 inpatients with proven COVID-19, SARS-CoV-2 ribonucleic acid (RNA) could be detected in 93% of bronchoalveolar lavage fluid specimens, 72% of sputum, 63% of nasal swabs, 46% of fibrobronchoscope brush biopsies, 32% of pharyngeal swabs, 29% of feces, and 1% of blood samples.16 Another study using a different methodology and timing of specimen collection showed viral RNA could be detected in blood samples (40% of patients) and anal swabs (27% of patients) even after the oral swabs became negative.17 Three other groups reported a rate of positive blood detection of 10% to 17% of patients, including in nonfebrile and asymptomatic carriers.9,18,19 In some studies, the detection of viral RNA in blood was a strong indicator of future clinical severity.18 So far, the virus has not been detected in urine samples.16 Together, these results suggest there might be a shift in virus distribution from the respiratory tract early on to the gastrointestinal tract later on, with viremia possibly persisting for some time after the resolution of the respiratory tract infection or in asymptomatic carriers.17 This has significant implications for COVID-19 diagnosis, as the sensitivity of tests will be influenced by both the tissue sampled and the timing of the sampling. A concerning finding for neurosurgeons is the hypothesis that SARS-CoV-2 might have tropism for the CNS.20,21 There is accumulating anecdotal evidence that anosmia and associated dysgeusia could be symptoms of COVID-19 even in the absence of other respiratory manifestations. Such an observation was also made in a SARS patient,22 and transgenic mice models have demonstrated that SARS-CoV could infect the olfactory bulb neurons and reach the CNS through trans-synaptic spread.23 There is so far only one published report of SARS-CoV-2 detection in the cerebrospinal fluid (CSF) of a human patient24 and no study demonstrating complete virions in either the CSF or the CNS. However, this possibility should be kept in mind and has been proposed by some authors to explain the lack of central breathing drive observed in many intubated severe COVID-19 cases.21 Shedding and Transmission Detection of viral RNA by polymerase chain reaction (PCR), however, does not imply the existence of intact, infectious viral particles. To be transmitted, the complete and assembled virus needs to be shed by the contaminated host and transported to an entry tissue in a new potential host. So far, the presence of live virus shedding was confirmed from human airway epithelial cells1 and feces specimens, occurring even in patients who did not have diarrhea.16 There is no evidence yet that the fully assembled virus can be detected in the blood, although a controversial study during the 2003 SARS epidemic suggested that blood transmission of SARS-CoV occurred in Hong Kong25 and many blood transfusion agencies are refusing blood donations from COVID-19 patients.26 Once outside of the contaminated host, SARS-CoV-2 virions have a half-life of 1.1 h in aerosols, 3.5 h on cardboard, 5.6 h on stainless steel, and 6.8 h on plastic.27 These observations suggest SARS-CoV-2 infection can occur via direct or indirect transmission. Direct transmission can occur through contact (eg, kissing an infected individual) or droplets (eg, inhaling virion-containing aerosols immediately after an infected patient coughed, sneezed, or talked). Indirect transmission can occur through fomites (such as touching a contaminated surface and then touching one's mouth or nose) or through airborne transmission (such as aerosolization of virions during medical procedures). The current consensus is that SARS-CoV-2 is transmitted primarily through the respiratory and possibly fecal-oral routes.1,28 There is no evidence so far for blood transmission26 and there are conflicting reports on vertical transmission from a pregnant woman to her fetus.29,30 The magnitude of the pandemic highlights how infectious SARS-CoV-2 is. Early estimates of the basic reproduction number (R0) range from 2.2 to 6.49 people infected by every contagious individual, compared to 1.28 for the common flu and 1.46 for the H1N1 2009 pandemic.31,32 This might be explained by the existence of contagious asymptomatic carriers,33 which might represent 17.9% of infected individuals, including a high proportion of children.34 SARS-CoV-2 Virus and Immunity Testing The current gold standard for COVID-19 diagnosis is through the detection of SARS-CoV-2 RNA using reverse transcription polymerase chain reaction (RT-PCR) on respiratory material (typically a nasopharyngeal and/or oropharyngeal swab).35 The specific gene target, primers, and probes used are highly variable across countries, as are the specimen analyzed (eg, upper respiratory, lower respiratory, blood, stools) and the timing of specimen collection. As such, no reliable data are currently available on the sensitivity and specificity of COVID-19 testing. While a South Korean study of 10 cases suggested a false-negative rate of 20% for RT-PCR,36 larger studies will be required to confirm this finding. Meanwhile, new point-of-care tests are also in development and will use different technologies, such as immunoassays and clustered regularly interspaced short palindromic repeats (CRISPR), which will again require validation.37 There is no test available yet to confirm the immune status against SARS-CoV-2,37 although combined IgG-IgM assays can now assess exposure.38 GENERAL MEASURES TO PREVENT PERIOPERATIVE NOSOCOMIAL SPREAD In China, 3.8% (1716 of 44 672) COVID-19 cases occurred in healthcare workers, with 14.5% of these (254) considered severe and 5 leading to death.39 Later reports suggested the first nosocomial spreading event occurred during a pituitary surgery in which 14 people present in the case were infected.40 Infected personnel can act as vectors for disease propagation before becoming symptomatic, quarantined, and unable to deliver care. General measures are being implemented in most hospitals to prevent perioperative nosocomial spread of SARS-CoV-2. One of the most detailed and impressive reports of such measures comes from a large tertiary hospital in Singapore.5 This group applied the “hierarchy of controls” framework41 to the COVID-19 pandemic to reorganize their OR environment and workflows, as detailed in Table 1. The framework suggests that the most effective way to protect from a hazard is elimination (physically remove the hazard). If impossible, fallback options are substitution (replacing the hazard), followed by engineering controls (isolating people from the hazard), followed by administrative controls (changing the way people work), and, lastly, protecting workers using personal protective equipment (PPE). Each institution will have its own protocol and it is critical that all personnel be familiar with the local procedures. TABLE 1. - General Measures to Prevent Perioperative Nosocomial Spread as Implemented in Singapore5 Hospital measures related to surgery and anesthesia: Reduce elective activities to increase capacity and accommodate infection prevention measures Screening of patients, visitors, and staff for symptoms or travel history Setting up efficient communication channels with staff (COVID-19 website, helpline for anxiety and burnout) OR management: Reserve a specific OR area for COVID-19: Independent, negative pressure ventilation Physically isolated from the main OR Control traffic by locking all but the scrub room door during surgery Assign an anesthetic team exclusively for COVID-19 patients Design and teach new workflows for COVID-19 patients Anesthesia staff training and management: Formal N95 fitting sessions Formal training sessions on PPE use Segregation of staff between hospitals to minimize the risk of nosocomial spread from one hospital to the other Attendance tracking on all face-to-face meeting to facilitate contact tracing in the event of an outbreak Postponement of all nonurgent preoperative visits Pregnant or immunocompromised staff did not care for COVID-19 patients Mandatory use of PPE: When caring for low-risk patients (asymptomatic and no history of travel or contact with COVID-19 patient): surgical masks and droplet precautions When caring for high-risk patients: N95 masks, eye protection, gown, and gloves When caring for COVID-19 patients: N95 masks, eye protection, gown, and double gloves When performing aerosol-generating procedures on COVID-19 patients: powered air-purifying respirator Specific measures when caring for COVID-19 patients Patients should wear a surgical mask during transport Patients are transported using a designated route minimizing the risk of encounter Keep the COVID-19 OR as empty as possible and only bring equipment and drugs as needed Use single-use equipment as much as possible Do not bring paper charts into the COVID-19 OR Cover all monitors, computers, and machines in plastic wrap Perform the patient review, induction, and recovery within the OR to limit contamination to a single room Limit the number of staff in the OR Limit the movement of staff in and out of the OR OR decontamination after COVID-19 surgery Discard the anesthetic breathing circuit and soda lime canister Clean all surfaces with quaternary ammonium chloride disinfectant wipes Clean OR with sodium hypochlorite 1000 ppm Treat OR with hydrogen peroxide vaporization or ultraviolet C irradiation All staff to shower and change into new scrubs after each COVID-19 case Perform a series of simulations and walkthroughs of the COVID-19 workflow NEUROSURGERY-SPECIFIC RISKS AND MITIGATION STRATEGIES In neurosurgical practice, we anticipate 3 settings where the risk of SARS-CoV-2 transmission in the OR might be the highest: during endotracheal intubation and extubation; during surgeries exposing the respiratory or digestive tracts; during the use of instruments producing aerosolization of virion-contaminated tissues. Understanding these high-risk settings provides an opportunity to optimize our procedures to minimize nosocomial transmission. Risk Related to Endotracheal Intubation and Extubation Airway manipulation represents a significant risk of respiratory infection transmission among healthcare workers. In a 2012 systematic review, endotracheal intubation had a hazard ratio (HR) of 6.6 (95% CI 4.1-10.6) for respiratory virus transmission, over tracheotomy (HR = 4.2, 95% CI 1.5-11.5), noninvasive ventilation (HR = 3.1, 95% CI 1.4-6.8), and manual ventilation before intubation (HR = 2.8, 95% CI 1.3-6.4).42 Guidelines for the management of airway in COVID-19 patients have just been published43,44 and should help anesthesiologists mitigate this risk as much as possible, especially given the higher contagiousness of COVID-19.32 What neurosurgeons can do to help, however, is to reappraise the necessity for general anesthesia (GA) and endotracheal intubation in their patients. Many procedures routinely performed under GA in most centers can easily and safely be accomplished under conscious sedation, local anesthesia, and/or spinal anesthesia with the patient wearing a face mask to limit aerosolization in the OR. These include external ventricular drain (EVD) placement, chronic subdural hematoma (CSDH) evacuation,45 carotid endarterectomy,46 and lumbar discectomy or laminectomy,47,48 among others. If GA is absolutely required, all unnecessary personnel (including most neurosurgeons) should not be in the room while intubation and extubation are performed. Awake fiberoptic intubation should be avoided if possible, as should any procedure that might induce coughing.49 Risk Related to Respiratory and Digestive Tract Exposure Given the biodistribution of SARS-CoV-2, procedures involving the respiratory tract generate the highest risk of nosocomial transmission. Anecdotal, unpublished reports from China suggest that ENT surgeons might be the most affected of all healthcare workers. For neurosurgeons, this risk arises during trans-sphenoidal approaches, transmastoid approaches, transoral approaches, percutaneous trigeminal rhizotomies as well as craniotomies involving the frontal sinuses, such as bicoronal, bifrontal craniotomies or frontal skull fracture repair. In the setting of a local outbreak or in COVID-19 positive patients, surgeons should try to delay these procedures or use alternative approaches, wherever possible. Most trans-sphenoidal surgeries, for instance, are performed for benign lesions that can usually be delayed until after the pandemic, or at least after the patient's COVID-19 status is negative. For procedures that cannot be postponed (eg, pituitary apoplexy, craniopharyngioma with obstructive hydrocephalus), serious consideration should be given to a transcranial approach (eg, pterional) or an alternative strategy (eg, a cystic craniopharyngioma could be drained through stereotactic implantation of an Omaya reservoir and treated using intracavitary therapies rather than trans-sphenoidal resection). The same applies for translabyrinthine approaches for vestibular schwannomas, which can usually be substituted for a retrosigmoid craniotomy. Whenever performing a craniotomy, extra care should be placed in avoiding the frontal sinuses or mastoid air cells, which can be facilitated by the use of neuronavigation. In frontal sinus fractures, conservative treatment or lumbar drainage could be attempted until COVID-19 status is negative. Patients with trigeminal neuralgia could be offered radiosurgery over rhizotomy, if pain control cannot be achieved pharmacologically. For spine tumors or trauma, dorsal approaches should be favored over transthoracic surgeries to minimize the risk to the lung parenchyma. When exposure to the respiratory tract is unavoidable, patient decolonization could be attempted in COVID-19-positive patients. Along with standard chlorhexidine skin preparation, intranasal povidone iodine preparation (especially in and chlorhexidine or hydrogen peroxide mouth have been although the of this approach The of the gastrointestinal tract can also increase the risk of SARS-CoV-2 infection if a in this could if the is during an approach to the if an is through the or if the is during should be as to these and should the PPE and OR decontamination protocol if they during a For under direct be as to of the should also be given to third when Risk Related to on A most yet highly risk by neurosurgeons is an airborne transmission of the virus from the use of aerosol-generating These include all powered as well as used for during To be to contain This is the case in the respiratory and digestive studies are for CNS and while the clinical of blood As discussed SARS-CoV-2 RNA can be detected in the blood of 10% to of COVID-19 While RNA detection does not imply the presence of complete viral our in the case of SARS-CoV-2 is It therefore to limit the use of aerosol-generating instruments if possible, in the setting of COVID-19-positive if a nosocomial spread of is occurring or if the surgical approach exposure or to the sinuses or In any of these and should be favored over with a can be performed using a or a rather than a especially for or where a single be In trans-sphenoidal and can In the setting of spinal and can usually be achieved with and probes are suggested to facilitate the of In any case where is the could be used at lower and should be stopped when should be used to as much as possible and the area using a (eg, or could be In spine the use of as well as such as procedures and percutaneous should be considered to lower the of from should be immediately The use of and should be could be performed rather than to the aerosolization by the aerosol-generating instruments should be by rather than of these precautions (including the of have been by a group of neurosurgeons in Wuhan where most of the however, was on and the time of SARS-CoV-2 When surgery is required and but not systematic SARS-CoV-2 of low-risk and asymptomatic patients should be considered on the local and of Given that 17.9% of infected individuals might by asymptomatic this has the potential to nosocomial spread while PPE in the of This be achieved by procedures after infected patients are and the use of more PPE in negative The however, is that until COVID-19 tests are and their sensitivity and specificity at the local a negative test might a of and increase nosocomial transmission. authors have the COVID-19 to this high possibility of patients with a high clinical of COVID-19 infection with a negative test should be considered as Patients should also be to precautions in the between the and the some healthcare workers will some against SARS-CoV-2, either they and from the disease an effective will While immune is not yet its development should to the OR by the care of COVID-19 patients to immune The COVID-19 pandemic is a of proportion in As we are this it is to the of that has been in the 3 the existence of the SARS-CoV-2 virus was first the complete RNA sequence as well as of the are available on and sites of entry, virus biodistribution as well as shedding and transmission. this tests are being are being and procedures to the spread of the virus are being While not on the frontline of any of these neurosurgeons can by their to prevent nosocomial infection of patients and healthcare workers. This can be achieved by some in neurosurgical procedures to our current of SARS-CoV-2 and transmission. Table general perioperative measures implemented in where the outbreak was well have been published and might be of to OR Table 2 general measures that are of importance to These include the number of surgeries the number of individuals in the and performing preoperative possible. TABLE - General Measures of to the COVID-19 on as patients as surgeries that cannot be delayed When an alternative to surgery and is the alternative If the healthcare system only surgery to patients who have a as people as possible in the surgical Keep the number of individuals in the OR to the required for of the surgery Do not and even who do not have an personnel by and minimizing surgeons in specific hospitals to minimize nosocomial transmission from one hospital to If possible, all COVID-19 patients to a single team that will minimize with other surgeons Once immune status available and and COVID-19 patients to staff with proven on local and all surgical patients for SARS-CoV-2 or all patients as infected Table 3 suggests possible to standard neurosurgical procedures that have the potential to limit nosocomial transmission. These are at 3 high-risk settings in the neurosurgical endotracheal intubation and respiratory or digestive tract and aerosolization of virion-containing particles. TABLE - to general anesthesia possible to minimize the risk of aerosolization associated with endotracheal intubation and extubation For surgeries, use a If intubation is required, all unnecessary personnel outside of the room during the If intubation is required, use to surgical approaches avoiding the sinuses and If exposing the nasal or oral intranasal povidone iodine preparation (especially in and chlorhexidine or hydrogen peroxide mouth nasal and nasal Given the current on the potential of viral transmission through blood or other such as the use of aerosol-generating using or of especially when in the of sinuses or mastoid Perform using a or rather than a For spinal and using rather than a and use probes to facilitate the of When is at lower the when Use large to try and all airborne the area using a (eg, or to limit the spread of airborne minimizing the of required in spine procedures by using and approaches, such as procedures and percutaneous using unnecessary using using performing rather than to minimize aerosolization the surgical with when to minimize aerosolization with large at pressure rather than at high pressure Given the of the the measures have not been in do not and should be as to be considered by neurosurgical as they this While they are all on a their clinical Most controversial is the to limit the use of aerosol-generating including and the that a respiratory virus could be transmitted by inhaling lumbar can be This require aerosolization of virion-contaminated blood or CSF with the which has been for SARS-CoV-2 for a surgical protocol should not be if it patient or the surgical however, is that in many aerosol-generating instruments can be substituted by other any negative patient In these be the for not being given that our of COVID-19 is that the small proposed in the of standard could have a significant on disease transmission the surgical of patients. might if they given the in in this What we do however, is that if we do not try and mitigate the spread in healthcare workers we will patients and in the The SARS-CoV-2 virus has and airborne transmission. In the neurosurgical high-risk settings include endotracheal intubation and procedures involving the respiratory or digestive and the use of aerosol-generating instruments on virion-contaminated tissues. In to general neurosurgeons can to the in the risk of nosocomial infection of healthcare workers by their in COVID-19 patients, high-risk and during local nosocomial include all nonurgent the necessity for alternative surgical approaches avoiding the respiratory and the use of aerosol-generating including and The authors have no or in any of the or in this

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