key: cord-1018278-6rrj1s1d
authors: Kunz, Yannic; Horninger, Wolfgang; Pinggera, Germar.‐M
title: Are urologists in trouble by SARS‐CoV‐2? Reflexions and recommendations for specific interventions
date: 2020-06-19
journal: BJU Int
DOI: 10.1111/bju.15141
sha: f7a1c95e75701482dc077d5c815437e61bd4f9b7
doc_id: 1018278
cord_uid: 6rrj1s1d

OBJECTIVE: We aim to assess the risk of infection during urologic surgeries. Therefore possible hazards in tissue, blood, urine and aerosolized particles generated during surgery, are evaluated. Understanding the risk, recommendations for clinical practice are provided. MATERIALS AND METHODS: Review of available literature on urological and other surgical procedures in patients with virus infections such as HPV, HIV and hepatitis B and current publications on COVID‐19. RESULTS: Several possible pathways for viral transmission appear in the literature. Recent groups detected SARS‐CoV‐2 in the urine and faeces, even after negative pharyngeal swabs. In addition, viral RNA can be detected in the blood and several tissues. During surgery, viral particles are released, aerosole‐borne and present a certain risk for transmission and infection. However, there is currently no evidence on the exact risk for infection by the substances mentioned above. It remains unclear whether or not viral particles in the urine, blood or faeces are infectious. CONCLUSIONS: Whether SARS‐CoV‐2 can be transmitted by aerosols remains controversial. In any case, standard surgical masks offer inadequate protection from SARS‐CoV‐2. Full PPE including at least FFP‐2 masks and safety goggles should be used. Aerosolized particles might remain for a longer time in the operation theatre and contaminate other surfaces, like floors or computer input devices. Therefore scrupulous hygiene and disinfection of surfaces must be carried out. To prevent aerosolization during laparoscopic interventions, the pneumoperitoneum should be evacuated with suction devices. The use of virus proof HEPA filters is recommended. Local separation of anesthesia/intubation and operation theatre can reduce the danger of viral transmission. Lumbar anaesthesia should be considered especially in endourology. Based on current knowledge, COVID‐19 is no contraindication for acute urological surgery. If possible however, as european guideline committees recommend, non‐emergency urological interventions should be postponed until negative SARS‐CoV‐2 tests become available.

Since December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection disease , first described by WHO on 30 January 2020 as a public health emergency of international concern, and then on March 11 as a pandemic, has been spreading rapidly worldwide, posing a major threat to people and severely burdening the healthcare system as well its caretakers. [1, 2] COVID-19 is a contagious pulmonary infectious disease with respiratory symptoms similar to those seen in the previously reported SARS epidemic in 2003 or Middle East respiratory syndrome (MERS) in 2012. 1 [3] Similar to other viruses with pandemic potential including H1N1, H5N1 and H5N7 influenza viruses, and similar to the severe acute respiratory syndrome (SARS) or MERS in the past, the primary transmission of human coronaviruses (hCoV) is believed to occur principally through direct contact transmission (independent of surface contamination), respiratory droplets from coughing and sneezing and airborne routes. [4] This infection route may significantly rise in the case of elevated aerosol contaminations in closed spaces. the infection rate for SARS-CoV-2 due to any virus spread by inanimate surfaces, where COVID- 19 can survive for many days [4, 5] , by air samples from an intensive care unit (ICU), operating theatre or general COVID-19 wards as well by the use of surgical equipment has to be further evaluated.

Even though urologic patient occurrence already drops [6] , a significant number of patient presentation will persist. While elective urologic procedures can be postponed for at least some days or weeks probably without any real risk to patients, emergency and oncologic operations need to be carried out without any delay. Standard measures for the safety of emergency personnel and anesthetists are always in place, but due to possible exposure to SARS-CoV-2 contaminated aerosols, surgeons too might need personal protection equipment. To avoid any SARS-CoV-2 infection, all healthcare workers during urologic surgeries need to be appropriately protected. This poses the question if urologic surgery is safe and acceptable under such a perspective in 2020 and beyond? Acute surgical interventions will continue to be necessary to prevent danger to patient health. We reviewed recent studies to illuminate backgrounds and offer guidance to clinicians in this specific field.

The main types of urologic surgery are so-called open surgery, laparoscopy -with or without robotic assistance -, and endourologic surgery. In the absence of recommendations in the guidelines of urologic societies, we will focus here on the infection risk arising from urologic surgeries such as laparoscopy and endoscopy.

Laparoscopic surgery, a minimally invasive approach, offers some advantages in the urologic field and is a well-established technique for many indications. It reduces hospitalization time, resources and occupation of intensive care units; any personnel and resource sparing option are generally considered crucial right in times of the ongoing COVID-19 pandemic disease. Furthermore, surgical complications are reportedly less common in laparoscopy compared to classic open surgical interventions. [7, 8] Despite that, some concerns about possible infection via aerosols originating from the pneumoperitoneum have been mentioned recently, especially in gynecology. [9] [10] [11] SARS-CoV-2

Around the globe, as of today roughly 5.4 million people are infected with the SARS-CoV-2 with an absolute fatality of over 324.000 cases, and 169.000 deaths registered in Europe alone. 2 3 The daily number of confirmed infected and fatal cases is increasing and the climax is far away. An unknown number of asymptomatic people represent as a possible source for spread of infection. Indeed, a substantial number of cases are underdiagnosed. The incubation period for COVID-19 is between 5 and 14 days. [12] Therefore, virus transmission from a pre-symptomatic case can occur before symptom onset. This must be considered as a risk during surgery. Whereas according to the WHO data, asymptomatic infections in the European Union are between 1% and 3%, some researchers estimate it to be around 30 %.

[12] Among the Japanese patients evacuated from Wuhan, the center of the coronavirus outbreak, 30.8% were asymptomatic but in close contact with SARS-CoV-2 infected people (95% confidence interval (CI): 7.7%, 53.8%). [13] SARS-CoV-2 can be diagnosed by a combination of clinical evaluation and imaging procedures: thoracic CT scan shows typical abnormalities with ground-glass opacity and bilateral patchy shadowing in over 80%. The chest CT scan usually has superior detection rates compared to thoracic radiography which detects 59% abnormalities. [14] The WHO recommends collecting specimens from the upper respiratory tract (naso-and oropharyngeal samples) or the lower respiratory tract (e.g. expectorated sputum or endotracheal aspirates), suitable for genomic RT-PCR analysis. The infectiousness (basic case reproduction rate (BCR)) varies between 1.9 to 6.47 new infections per patient. [15] [16] [17] [18] [19] In a selected, but representative random sample population of 1,544 persons tested between 1 st to 6 th April in Austria, 0.33 % of the subjects tested positive for SARS-CoV-2 by RT-PCR measurements, thus allowing an estimation of a nationwide total of acute -in terms of RT-PCR positive tested-persons between 10,200 and 67,400 4 . Due to the study protocol, the analysis addressed only the acute infection rate and not any recent or past contact with SARS-CoV-2. Therefore, in one other study, 2822 persons from two hot spot regions in Tyrol, (Ischgl and St. Anton, Austria) were investigated. The analysis showed a higher prevalence of 

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The high number of diagnosed or suspected cases together with the high infectiousness of the novel SARS virus underlines the need for clinicians to carefully plan all their treatment modalities for ordinary diseases in their specialty. showed positive results by RT-PCR. Notably, for this SARS disease, the viral shedding peak in urine occurred even later, namely at weeks 3-4; but the urine specimen RT-PCR remained still positive for many weeks after infections. [24] In a large study by Hung et al, the detection rate of positive urine findings was 28.8% (32 out of 111 pts.). Similarly, viral RNA was detected in 31 of 74 urine samples (42%) collected at a mean of 15.2 (1.7) days after onset of symptoms. [25] Again, urine specimens (n = 133) from 101 patients suffering from SARS-CoV were collected yielding out a positive rate by RT-PCR measurements in 25% and remarkable, until the 45 th day after infection. [23, 26] 

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On the other hand, in Lescures workgroup, a very small collective of only five patients with SARS-CoV-19 showed no viral load in the urine. [27] Another recent publication failed to find SARS-CoV-2 RNA in any of the 42 tested patients.

All these findings are crucial for all endourologic interventions and personal safety of surgeons and health care workers involved. Therefore, minimising the risk of urine-borne infection is advised. Usually closed pumping systems for urine and irrigation fluid are commonly used in endourology. In patients with confirmed SARS-CoV-2 infections, a systematic use of these systems is definitely recommended [28] . Monitor-equipped systems allowing some distance to the surgical field are used nowadays. Closed continuous flow irrigation systems probably cause a certain dilution effect of the virus load in the urine as well as of the excised tissue. While a certain threat seems to be present, we consider endourologic procedures as safe in terms of COVID-19. The viral load in the urine is at a maximum below 10 %. A review of the current literature showed no data for any kind of viral disease transmission via aerosols or droplets during TURB or TURP. Therefore, in our opinion, the risk of aerosol generation by electrosurgical devices in TURB and TURP is negligible. Nevertheless, secure PPE and FFP-2 masks should be used for any SARS-CoV-2 suspected patient, especially if anaesthesia with tracheal intubation is performed in the same operating room. Lumbar anaesthesia is a valid alternative in many cases to reduce the risk of aerosol generation, thus eliminating the largest risk factor to contract with SARS-CoV-

Laparoscopy Generally, laparoscopy poses a significantly higher risk of generating aerosols by the establishment and maintenance of an artificial pneumoperitoneum. During laparoscopy, there is a large so-called surgical smoke formation in the pneumoperitoneum due to harmonic or ultrasonic scalpels, lasers, and other electrosurgery. Hereby, heat by diathermy causes cell membranes to rupture and generates a plume of smoke containing mostly water vapour (95%) and around 5% cellular debris of different sizes (0.007µm up to 0.31µm) in the pneumoperitoneum. Thus, surgical smoke contains blood and tissue particles, bacteria or viruses (or at least part of it), and represents a potential risk for surgeons and all other persons in the operation theatre. It is not the surgical smoke itself that is critical as long as it

This article is protected by copyright. All rights reserved remains in the "closed" body cavity, but rather any uncontrolled decompression of the pneumoperitoneum: this can occur at the end of the surgery or during tissue extraction, or by any leaky system of the insufflation / deflating system with gas expulsion via ports or trocars. Herein exists the risk of release of pneumoperitoneum-associated aerosolization of smallest particles of <5 μm in the surgical room. Compared with droplets, which are heftier and thought to travel only short distances after someone coughs or sneezes before falling to the floor or onto other surfaces, aerosols can linger in the air longer and have a larger spreading radius. SARS-CoV-2 can survive for several hours in aerosols and droplets, and because of gravity and airflow, most droplets can sink to the ground or on other surfaces in the operation theatre. Investigation of detectable viable SARS-CoV-2 viruses in a 3-hour experiment showed that the infectious titer dropped from 10 3.5 to 10 2.7 TCID 50 (50% tissueculture infectious dose) per litre of air. The half-lives of the virus in aerosol was around 1.1 to 1.2 hours. [30] Nevertheless, it must be emphasized that to our best knowledge, there are no data linking risk of being infected with SARS-CoV-2 and exposure of the operating room team during surgical procedures . On the other side, virus load was detected in such surgical smoke in cases of hepatitis, HIV or papillomavirus patients. [31, 32] The risk of occupational human papillomavirus transmission from patients to medical personnel during laser vaporisation or laparoscopic interventions was studied intensively but remains controversial. [33] Although the possibility of disease transmission through surgical smoke exists in humans, documented cases of pathogen transmission by aerosols are rare. Indeed, in contrast to the viral load in the blood or stool of affected patients, there has not been any increased risk of transmission from the surgical plume or laparoscopic pneumoperitoneum documented in the last decades.

Standard surgical masks offer less protection from contamination by aerosols compared to droplets. FFP-2 or -3 masks appear therefore definitively reasonable in the case of suspected COVID-19. Viral diseases are not in themselves a contraindication to surgery. [34] For example, patients with HIV or hepatitis commonly undergo surgery with certain precautionary measures in place.

However, whether SARS-CoV-2 can be transmitted by aerosols remains controversial, and the exposure risk for close contacts has not been systematically evaluated. Compared to droplet-borne infection, transmission via aerosol generated in the operation theatre seems

This article is protected by copyright. All rights reserved to be more likely. [11] It must be kept in mind that aerosol formation might remain for a longer time in the surgery room and contaminate other surfaces, floors or computer input devices etc.

Despite earlier pandemics, no useful information exists for healthcare worker infection during laparoscopic surgery with comparable diseases such as SARS-CoV, MERS-CoV or influenza. However, some data suggests faecal-oral transmitted infection of SARS-CoV-2. This is not surprising, since aside from the typical respiratory symptoms [fever (47%), dry or productive cough (25%), sore throat (16%), and general weakness (6%)], diarrhoea nausea, vomiting, and abdominal discomfort has been described. These clinical findings can be correlated to direct viral detection in biopsy specimens or stool examinations. Interestingly, viral RNA in the faeces persists even after symptom resolution and negative nasal RT-PCR .

Cai et al found a high frequency (83.3%) of SARS-CoV-2 RNA detection in faeces in mild paediatric patients and prolonged virus RNA shedding in faeces for at least 2 weeks and even more than 1 month. [35] This is primarily a concern for abdominal surgeons, but also affects urologist in complex oncologic procedures such as cystectomy with simultaneous orthotopic neobladder formation. Viral RNA was extracted with rectal swabs and stool samples in over 60% in patients testing positive for COVID-19 as well as many days after a negative oropharyngeal swab. [36] All stool-related aerosol contamination and infection risk has to be investigated in detail. Urine-borne contamination is, as stated earlier, a rare situation. Although viral shedding in blood is common (even in lower concentrations), 6 

This article is protected by copyright. All rights reserved All these aspects suggest that low-pressure laparoscopy should be applied. [38] The use of a closed system with careful smoke evacuation together with specific filters is to be recommended. Besides, the pneumoperitoneum may be cleared directly by closed suction devices. Personal protective equipment (PPE), in addition to the already fluid-resistant clothing in use, should be used. Especially FFP-2 or FFP-3 masks, protective glasses and single shoe covering are mandatory.

However, laparoscopy appears generally to be less a threat than any intubation intervention before operation. Therefore, intubation outside the operating room is advised whenever possible.

Laparoscopic kidney surgery takes a special role in this context since kidney tissue can be infected with SARS-CoV-2. [39] Immunohistochemistry has shown that SARS-CoV-2 NP antigen accumulates in kidney tubules, and virions and virus-like particles in kidney cells were detected by transmission electron microscopy. Haematoxylin and eosin staining of renal tissue identified that SARS-CoV-2 infection mainly induces severe acute tubular necrosis and lymphocyte infiltration leading to acute renal failure in around 25-30% of patients. [40] This is not surprising since SARS-CoV-2, once having passed through the mucous membranes, especially nasal and pharyngeal mucosa enters the lungs through the respiratory tract. Here a viremia is observed and the virus attacks targeting organs that express ACE2 receptors e.g. the kidney. [28] As stated above, electrosurgical or ultrasonic devices create aerosols when used. This is the case in most procedures of partial tumour nephrectomies, thus special precautions need to be taken. The aerosols generated while cutting kidney tissue could be infectious. In contrast, such risks have to be weighed against laparotomy, where direct exposure of the medical staff to the aerosols generated can be assumed. Thus, extraction units can be used for direct suction but need to be very potent assuring continuous inflow capacity. Laparoscopy in most cases is already equipped with good suction devices and might, therefore, be preferred. Besides, since kidney surgery is often done retroperitoneal, the risk of exposure seems less in comparison to abdominal laparoscopic surgery. The potential contact with urine, especially in kidney-sparing surgery can be neglected since SARS-CoV-2 RNA has not been reported in many urine samples.

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In laparoscopic cystectomy, a higher probability of viral transmission is suspected since the lancing of the intestines is necessary. As stated before, the stool can be hazardous in terms of COVID-19. Besides, the procedure is done transperitoneal. Possible contamination of the urine adds minimally to the general risk.

Prostate biopsy is an essential part of the urological routine. Main risk factors for COVID-19 transmission during this procedure are the possible contamination with blood and faeces, as well as to a lesser extent, urine. As described before, SARS-CoV-2 can be detected in all three cases, though the exact hazard is still unknown. [20-27, 36, 37] The specimen itself can be processed normally, since to date, a contamination of prostate tissue has not been detected. [41] To our experience, the putative risk for contamination might be highest whilst extracting the needle in order to process the specimen. In this case, especially face shields seem promising. Still, FFP-2 or -3 masks as well as PPE will be necessary since the suspected or confirmed COVID-19 patient is within reach. As an alternative, perineal biopsy can be discussed. However, since there is no hard data on faecal virus transmission, transrectal biopsy is considered reasonable within the common indications.

Even though a lot of the pathogenesis of SARS-CoV-2 infection in humans remains unclear, some researchers found that there are many pathologic findings in COVID patients. Among alterations in several cytokines, coagulation parameters such as D-Dimer increase is often observed (D-Dimer value is 4 times higher than the normal upper limit). Inflammation, infection and other factors can lead to excessive activation of coagulation. This is clinically seen by increased development of disseminated intravascular coagulation (DIC) in COVID-19 patients, mainly in severe types. [42, 43] Therefore, some clinicians are recommending an anticoagulation therapy with a dose of LMWH by subcutaneous injection of 100 IU per kg body weight twice a day in the first week. However, such flanking anticoagulation therapy is accompanied by higher risk of bleeding especially during urologic surgeries, requiring more careful intraoperative coagulation. [44] Accepted Article This article is protected by copyright. All rights reserved Some specific concerns in urologic surgeries SARS-CoV-2 virus is part of the coronaviridae family and has been meanwhile completely sequenced with the GeneBank entry MN908947. [45] The entry describes an RNA virus with an RNA sequence of 29033 bases. It was discovered that this new virus had around 80% and 50% genomic similarity to SARS-CoV and MERS, respectively. The SARS-CoV-2 is a large-sized virus approximately 120 nm in diameter (diameters vary from about 60 to 140 nm). [46] This might be considered for the infection's way of transmission by respiratory droplets due to cough and sneezing from COVID-19 patients as well for the aerosol formation. It was calculated that the virus spread of droplets < 10 microns can range 1.5 m by exhalation (breathing v 0 = 1m/sec), but 2 m for coughing (calculated velocity v 0 10 m/sec) and up to 6 m for sneezing (v 0 = 50 m/sec). [47, 48] With this knowledge in background, investigators studied the virus load in different areas in contact with COVID-19 patients. They investigated the virus load on floors, computer mice, trash cans, sickbed handrails, patient masks, PPE, and air outlets. The floor swab samples in ICU units showed a higher contamination rate of over 40%, compared to the general COVID-19 ward with 7.9% respectively. One explanation from the authors might relay to gravity and airflow causing most virus droplets to sink to the ground. To our best knowledge, no operation theatres have been investigated so far. Half of the samples taken from the shoe soles of the ICU medical staff tested positive and therefore, these shoes might function as carriers.

Furthermore, according to this study, there was an unexpectedly high rate of positivity for the surface of objects that were frequently touched by medical staff or patients: The highest rates were for computer mice (ICU 6/8, 75%; GW 1/5, 20%), followed by trash cans (ICU 3/5, 60%; GW 0/8), sickbed handrails (ICU 6/14, 42.9%; GW 0/12), and doorknobs (GW 1/12, 8.3%). [49] Contamination, therefore, can be expected also in the operation theatre when there is uncontrolled virus shedding due to aerosol formation during or after urologic surgeries.

Thus, the air condition in the theatre has to be specifically controlled and monitored. Air 

This article is protected by copyright. All rights reserved Granular Materials"), not only the porous diameter in the HEPA fibre is relevant, but other flow-related capturing mechanisms known as the inertial impaction, interception, and diffusion mechanisms are even more relevant. Scientists have found other additional physical aspects that need to be considered such as straining and electrostatic attraction, concluding that under certain circumstances, even with well-determined airflow and pressure rates. Therefore, is not alone the particle sequestration determined in respect to the net virus size by the HEPA filters relevant, because several other additional features must be respected. 

Starting in March and April 2020, European and American societies offer evidence based Guidelines for urologists. Starting with the prioritisation of surgical procedures, the EAU (European Association of Urology) [51] as well as expert groups [52] , [28] , [53] [54] advises therapy on malignancies and emergencies alone. Both societies aiming to reduce resource expenditure and patient accumulation in the clinical as well as the ambulant setting while offering space in ICUs. This is supported by AUA (American Urologists Association), offering comparable diagrams for patient triage. [55] To ensure safety for medical personnel, preoperative COVID-19 testing is recommended if an infection is suspected. Suspects might include patients with respiratory symptoms and fever, as well as contact with confirmed COVID-19 patients or arrival from endemic areas. Preoperative testing in general is only advised if enough resource is at hand [54] and should be done in an outpatient setting. [51] Citing the WHO (World Health Organization), all major societies are in agreement, that any suspected COVID-19 patients need to be seen as confirmed until proven negative. In case of suspected or confirmed COVID-19, virus-proof masks (e.g. FFP-2 or higher), PPE including safety goggles and gloves is essential during any surgery. [54] [56] [51] [57] In accordance with our findings above, separate "COVID-19-OTs" using an autonomous ventilation system in a low-pressure environment should be installed. Physical separation of anaesthesia/intubation and surgery in order to reduce aerosolisation is commonly accepted. [51, 54] If specific procedures cannot be postponed and conservative treatment is not available or equivalent, experienced surgeons should perform with minimal personnel. Electric cauterisation, with mono or bipolar devices might be reduced to minimum intensity. Expert societies in laparoscopy, like SAGES and ERUS (EAU Robotic Urology Section) recommend closed suction devices, low pressure pneumoperitoneum and closed pumping systems in both laparoscopy and endourology. [51] [58] 

This article is protected by copyright. All rights reserved in terms of aerosol generation and droplet infection. Nevertheless, laparoscopic surgery has not been abandoned and is not regarded as a substantial danger to medical staff in cases of HPV, Hep B, and HIV patients. There is currently no evidence that SARS-CoV-2 infections occurred in conjunction with laparoscopic surgery. Still, in allegiance with urologic societies around the world, it seems rational to systematically use high quality PPE including at least FFP-2 masks and safety goggles. The deployment of proper suction devices in laparotomy and closed systems with smoke evacuation is recommended. Experienced surgeons should perform operations to reduce the risk of bleeding in hemodiluted patients while simultaneously decreasing the amount of plume and surgical smoke. Continuous-flow procedures might be the safest approach in endourology. Overall, to relieve wards and intensive care units, shorter occupation time after laparoscopy appears to be the most important argument.

None declared

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In general:

 Basic infection-prevention measures (hand hygiene, respiratory etiquette, physical distancing) should be promoted universally  limitation of inpatient and outpatient occurrence in the hospital to reduce virus spreading to a minimum for patients and health workers.

 prioritize patients according to major guidelines or in accordance to local specific requirements.

 suspension of all non-urgent elective surgeries by increasing the critical care capacity 

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Accepted Article This article is protected by copyright. All rights reserved

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