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Risk of SARS-CoV-2 contagion in otolaryngology specialists

SUMMARY COVID-19 has rapidly spread in the past two years with a profound impact on otolaryngological activities, which has undergone radical transformation to guarantee diagnostic and therapeutic procedures mainly in oncology and urgent patients, while ensuring protection for healthcare personnel and patients. During the initial phases of the pandemic, scheduled visits and elective surgeries were postponed leading to a delay in the diagnosis and treatment of several diseases, including head and neck cancer, with a shift toward more advanced cancer stages and more aggressive treatments. Aerosol and droplets are the main routes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus leading to a high risk of contagion during otolaryngology visits and surgery. Therefore, the correct use of personal protective equipment (PPE) and attention to procedure-specific risks and measures to avoid contagion are of utmost importance for healthcare professionals, and especially for those dealing with otolaryngology diseases. This narrative review highlights that otolaryngological activity implies a high risk of contagion during outpatient visit, surgery, or urgent conditions. The correct use of PPE, evaluation of procedure-specific risks and reduction of non-urgent procedures are considered the main strategies to limit contagion.


Introduction
In January 2020, a novel coronavirus disease  was officially announced by the World Health Organization (WHO), which rapidly developed into a worldwide public health emergency 1,2 .
COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The human coronaviruses (HCoVs) are members of the coronaviruses family, and responsible for multiple respiratory conditions including the common cold, bronchiolitis and pneumonia 3 . HCoVs periodically appear in different places around the world and have been linked with epidemic or pandemic human pneumonia since the beginning of the 21 st century 4 ; they include the severe acute respiratory syndrome coronavirus (SARS-CoV), in November 2002, and the Middle East respiratory syndrome coronavirus (MERS-CoV) in June 2012 5 .

SARS-CoV-2 characteristics
Generally, HCoVs are composed of some viral proteins: spike, membrane, envelope, nucleocapsid proteins and hemagglutinin. Spike, membrane and envelope proteins are inserted into the viral envelop, while nucleocapsid protein protects the viral RNA genome located in core of virus 6 . In particular, the spike protein is a glycosylated protein containing the receptor binding domain, which mediates viral entry into host cells 7 . Clinical aspects (symptomatic and asymptomatic infection) Several studies have documented the clinical severity of COVID-19. In most cases, the incubation period (initial infection to symptoms) varies between 0 to 24 days after exposure, with an average of 5-7 days 8 . Interestingly, COV-ID-19 positive patients may be an important source of viral transmission before developing symptomatic disease 9 . The most common symptoms are fever, dry cough, pharyngeal pain, headache and myalgia. Some patients complain of fatigue, shortness of breath, muscle pain, confusion, sore throat, headache, vomiting, diarrhoea, olfactory and gustatory dysfunctions and, more rarely, ocular inflammation such as kerato-conjunctivitis 10,11 (Fig. 1). Patients with severe disease typically present with fever, dry cough, dyspnoea, and interstitial pulmonary infiltrates on thorax imaging. Complications of COVID-19 include acute respiratory distress syndrome (ARDS), respiratory failure, liver injury, acute myocardial injury, acute kidney injury, septic shock and even multiple organ failure. In the case of severe complications, patients require invasive mechanical ventilation (IMV); the case-fatality rate varies between 36 and 52% 12 . The risk factors for disease progression are old age, male sex and presence of comorbidities like chronic obstructive pulmonary disease, hypertension, diabetes, coronary atherosclerotic heart disease and hepatitis B or liver cirrhosis 13 . In the literature, several studies confirm that one or more underlying diseases are correlated with worse prognosis 14 . Many cases of COVID-19 are asymptomatic, with positive detection of nucleic acid of SARS-CoV-2, but with no typical clinical symptoms or signs 15 . In these cases, the key point to control COVID-19 diffusion is the early recogni- tion of an infected person, but most persons with asymptomatic infection do not seek medical assistance, thus contributing to the rapid spread of SARS-CoV-2 16 .

Routes of virus transmission
The main routes of virus transmission include direct transmission through cough, sneezing and contact with oral, nasal and eye mucous membranes 17 . The transmission of infection can occur through both aerosol and droplets. Airborne transmission occurs through small inspirable aerosols (< 5-10 um) even over long distances, while droplet transmission occurs through passage of larger aerosols (> 5-10 um) directly from the infected person to the new host over short distances 18 .

Impact of COVID-19 on otolaryngological activity
Reorganization of otolaryngology services As a consequence of the outbreak of SARS-CoV-2, national health care systems around the world underwent profound changes. The activity of otolaryngological services has undergone radical transformation to guarantee diagnostic and therapeutic procedures mainly to oncology and urgent patients. A survey from the COVID-19 Task Force of the Young Otolaryngologists of the Italian Society of Otolaryngology Head and Neck Surgery 19,20 reported dramatic changes in ordinary clinical and surgical activity of otolaryngology units in Italy. Non-urgent outpatient procedures were temporarily suspended to limit viral diffusion, and healthcare personnel were relocated to dedicated COVID-19 wards 21 . Following international recommendations 22 , before entering the hospital, patients were called and queried about the onset of specific COVID-19-related symptoms in the previous two weeks or direct exposure to SARS-CoV-2, and body temperature was measured at admission; furthermore, normothermia with a negative nasopharyngeal swab for SARS-CoV-2 were required before entering the operating room.
Impact on otolaryngology procedures (elective, emergency, oncology) Urgent otolaryngology conditions are mainly represented by respiratory distress, epistaxis, sudden sensorineural hearing loss, peritonsillar and neck abscesses, haemorrhage of upper aerodigestive tract, foreign bodies, complicated otomastoiditis and traums. These are situations for which otolaryngology examination cannot be postponed and may require an upper airway endoscopy and/or an auditory evaluation.
Focusing on emergency department activity, in the literature a significant reduction of the number of visits has been described in comparison with the same period of previous years (62-68%) 23 . However, the most dramatic data is the reduction of the number of urgent services during the COVID-19 outbreak 24 . The reasons for the reduction of emergency otolaryngology interventions can be explained by various factors, including the fear of nosocomial SARS-CoV-2 infection, social distancing and home confinement. Head and neck cancer surgical activity during COVID-19 pandemic consisted mainly in oncology-related diagnostic biopsies (generally performed through microlaryngoscopy or endoscopy), endoscopic or open head and neck procedures and otologic and otoneurologic treatment 21,23 . Head and neck oncology multidisciplinary consultation meetings have been performed in video or teleconference to avoid delays in treating and exposing patients to the risk of infection. Telemedicine is another important tool that quickly developed during the pandemic to ensure medical examinations; in this way, access to the hospital was reserved only to patients who needed medical or surgical treatment 25 . In addition, telemedicine allowed medical examination for patients in follow-up after cancer treatment or remote evaluation of exams prescribed in previous visits.

Effects on otolaryngology patients' health
The drastic reduction of the routine activity of otolaryngology units had a dramatic impact on the services offered to patients during the pandemic. Scheduled visits and elective surgeries were postponed; this situation, associated with the patients' fear to contract the infection inside the hospital, led to a delay in the diagnosis and treatment of several diseases, including head and neck cancer, with a dangerous shift toward more advanced cancer stages and potential upstaging of TNM classification 26,27 . Some authors report a reduction of 10-20% in outpatient and surgical services in otolaryngology units, especially during the initial phase of the pandemic. For example, an increased interval between diagnosis and successive treatment was noted 28 . Delayed surgery and difficulties in guaranteeing adjuvant therapies also resulted in reduced overall survival for oncology patients 28 , tumour upstaging and need for more aggressive treatment, with extension of hospital stay, increased probability of postoperative complications and further reduction of beds. Furthermore, scientific evidence has confirmed that head and neck oncological patients are at high risk for COVID-19-related pulmonary complications, probably due to immunosuppression, impaired respiratory and swallowing function, and increased aspiration risk 29 .

Otolaryngology visits that favour SARS-CoV-2 transmission
Aerosol and droplets are the main route of transmission of SARS-CoV-2, thus leading to a high risk of contagion during otolaryngological visits and surgery. In fact, the viral membrane fuses with the host cell through cell-receptor angiotensin-converting enzyme 2 (ACE-2) and the mucosa of upper airway tract is rich of this receptor. Medical and surgical procedures for head and neck pathology may favour otolaryngologist, surgeon, nurse and anaesthesiologist contamination with patients' upper airway aerosol and droplets [30][31][32] . During outpatient visits, the otolaryngology specialist examines the nasal cavity, the oral cavity, the pharynx (naso-, oro-and hypo-) and larynx, requiring the patient to remove their face mask and often inducing sneezing and coughing. Moreover, during most otolaryngology urgent procedures, it is impossible to exclude COVID-19. For these reasons, the correct use of personal protection equipment (PPE) is of utmost importance for healthcare professionals and especially for those dealing with otolaryngological diseases [31][32][33] .

PPE: role in otolaryngology procedures
The protection of healthcare staff is fundamental to limit spread of infection. In the literature it is highly recommended the correct use of PPE during aerosol or droplets generating procedures. The most popular and widely used PPE are FFP2 or N95 respirator and surgical masks, goggles or face shield, glasses, caps, eye protection, fluid-repellent disposable, surgical gown and gloves 31,33 . The Canadian Society of Otolaryngology Head and Neck Surgery developed guidelines defining the level of protection for healthcare workers based on specific parameters. These include Level 1 PPE: Surgical mask + gown + gloves + eye protection; Level 2 PPE: N95 respirator + fluid repellent gown + head cover including neck protection + double gloves + eye protection; and Level 3 PPE: Negative pressure room with minimum staff + N95 mask with second surgical mask + face shield or goggles + double fluid repellent gown + head cover including neck protection + double gloves 34,35 .

Procedure-specific risk
Each otolaryngological surgical procedure implies a different risk of contagion. In this section, we describe the procedure-specific risk of the most frequent otolaryngology procedures and the strategy to minimise the possibility of contagion.

Endoscopy
Endoscopy of nasal, pharyngeal and laryngeal sites is routinely used in diagnostic otolaryngological activities and represents a high-risk procedure for otolaryngologists because it requires a short physical distance between patients and physicians and can induce sneezing and coughing 36 . Consequently, potential virus transmission through aerosol and direct contact can be generated, especially in cases of long exposure in closed environments 31 . National and international otolaryngology societies published several recommendations to limit contagion during endoscopy procedures. In general, the most frequent advice is to perform endoscopy with a flexible instrument in urgent cases and only if strictly necessary 36 . Another suggestion is to use topical decongestant with local anaesthetic solution during the examination 37 . In addition, during all endoscopic procedures, it is fundamental to use PPE and avoid direct contact with contaminated equipment and potentially harmful chemicals during the sterilisation procedures 38 .
Epistaxis management Epistaxis is one of the most common conditions in the general population and in some cases requires prompt treatment in an emergency department setting. Tunkel et al. 39 estimated that epistaxis accounts for about 0.5% of all emergency department visits and up to one-third of all otolaryngology procedures in the emergency department. As a general rule, all patients must be considered COVID-19 positive and appropriate precautions should be used. In addition, healthcare personnel should inquire about contacts at risk for COVID-19 and the presence of common COVID-19 symptoms like fever, cough or alterations in taste and smell in the last two weeks. When possible, patients should wear a surgical mask minimally covering the mouth. For proper management of epistaxis performed in the emergency department, it is important to distinguish patients who need prompt treatment from those who do not 40 . Table I summarises the clinical signs and symptoms of patients with epistaxis requiring immediate assistance. The first approach for epistaxis is non-invasive intervention, including compression of the alar cartilages for at least 15 minutes and administration of antifibrinolytic agents. If these attempts fail, more invasive interventions should be initiated. Ideally, invasive treatment should be performed in a negative-pressure operating room. In fact, nasal packing without anaesthesia or sedation can expose personnel to contagion because the patient is unable to control coughing and sneezing. Another recommendation is to reduce the number of personnel in the room, limiting to one otolaryngology specialist and a nurse. The most common treatments, which include nasal packing or cautery, should be performed in case of failure of non-invasive procedures or in case of a life-threatening epistaxis 40 . Nasal endoscopy with sphenopalatine artery ligation, in case of posterior massive epistaxis, should be delayed until COVID-19 testing is performed if clinically possible 41 . The last recommendation is that the first approach to epistaxis should be performed only by an expert physician, because errors in this phase can expose other healthcare specialists to the risk of accidental contact with contaminated medical devices.

Tracheostomy
The outbreak of SARS-CoV-2 caused a high-rate admission to hospitals and intensive care units (ICU). Tracheostomy was one of the most common procedures performed in sedated ICU patients who required prolonged intubation. The best timing to perform the tracheostomy in COVID-19 Table I. Risk factors and clinical signs and symptoms of epistaxis requiring prompt treatment.

Personal risk factors
High blood pressure not on therapy Haematological disease Oncologic disease Relapsing epistaxis Anticoagulant/antithrombotic therapy Clinical signs and symptoms Prolonged bleeding Bleeding from both sides of the nose Bleeding from the mouth Tachycardia Syncope Hypotension Hypovolaemic/haemorrhagic shock patients is still controversial, but systematic reviews suggest executing it from 7 to 10 days after orotracheal intubation to reduce the duration of invasive ventilation, mortality rate and length of stay in ICU 42 . However, it should be considered that tracheostomy in patients with severe forms of COVID-19 can also be detrimental. In fact, data in the literature demonstrate that in COVID-19 patients who underwent an extended period of mechanical ventilation, the tracheostomy might not be beneficial, and can increase the risk of SARS-CoV-2 infection in healthcare workers 43 . Table II summarises the most important factors reported in the literature regarding the timing of tracheostomy in COVID-19 patients. The execution of a tracheostomy can be done in sedated and intubated patient or in awake patients by local anaesthesia. It can be surgical (generally performed by otolaryngology specialists) or percutaneous (usually performed by anaesthesiologists). The latter is not preferable since airflow must be maintained during the procedure and droplet emission is higher 44 . Instead, during surgical tracheostomies it is possible to stop the airflow, although a large quantity of droplets and aerosol is usually generated after the aperture of the trachea and mechanical ventilation. In this scenario, the risk of exposure for surgeons, nurses and other healthcare personnel in operating room is very high. The procedure can be done bedside in ICU, although the most recommended setting is the operating room using negative pressure, when possible, even if this involves transfer from ICU and additional risk of exposure for medical staff. During the procedure, healthcare personnel protection is of utmost importance; some authors also suggest adopting powered air-purifying respirators (PAPRs) in addition to the standard PPE 45,46 . The surgical kits and cannulae of different sizes must be ready before the beginning of procedure to reduce entrance of other personnel in the operating room. During the surgical procedure, and especially before opening the trachea, it is important to perform deep muscular blockade, reduce the oxygen-percentage of the inflated air to 21%, push the tube as caudally as possible to avoid cuff breach and hyper-inflate the tube cuff to ensure lower air-way isolation. Post-operative management of tracheostomy patients includes safe suction of secretions, regular cuffpressure check and correctly planned cannula changes.
Endoscopic sinonasal and skull base surgery Endoscopic sinus and skull base surgery are some of the most widely performed procedures in otolaryngology and are considered high-risk operations for viral spread and infection of the operator 47 . The reasons are the high viral load in the upper airways, and especially aerosol generation during endonasal instrumentation, like suctioning, drilling and use of debrider and bipolar diathermy 48 . Many cases of surgeons developing COVID-19 symptoms after endoscopic surgery in patients without clinical manifestations of infection have been reported from China, Iran, Italy and Greece 49 . Spock et al. 50 proposed a COVID-19 management algorithm to stratify urgent and non-urgent cases requiring endoscopy procedures, dividing patients into non-neoplastic and neoplastic. During the first weeks of the pandemic, several strategies to limit aerosols produced during endoscopic sinus surgery (ESS) have been proposed. Tsagkovits et al. 47 suggested to place the surgical instruments on the thorax of patient and to wrap an otomicroscope drape around the patient in order to isolate the head and the body. According to Spock et al. 50 patients can be fitted with a rigid facial mask modified with a hole in correspondence of the nose, then placing a glove over the cutout (called 2-port VENT mask). Jones and colleagues 51 used a modified bronchoscopy mask over the face of patient; this tool, connected to a suction unit to reduce spread of aerosols and droplets, allowed the introduction of endoscopic instruments and orotracheal tube. After these first attempts, the main recommendations reported in the literature during endoscopic surgery are the following 52 : a) Perform the procedure with a skilled surgeon, dedicated operating room team (nurse and anaesthesiologist) and set of precision instruments; b) Minimise the spread of the virus from bone drilling, cauterisation and exposure to the heat generated by light from the endoscope; c) Especially for anterior skull base pathologies, use ESS only when it constitutes the best option with regards to ex- posure, resection and morbidity. In fact, in many cases of anterior skull base pathologies, minimally-invasive transcranial approaches may remain a better option to reduce the spread of virus during surgery.
Otologic and neurotologic surgery During the initial phases of the pandemic, there was no clear consensus on the safety of otologic surgery and causes of contagion during it. The initial hypothesis was that mucosal lining of the Eustachian tube, middle ear and mastoid should be polluted by the virus from the upper airway and drilling the mastoid bone can produce droplets and aerosols 53 . Moreover, in animal models and cadaveric simulation it was demonstrated that drilling bony microspicules could penetrate the cornea as a possible means for viral transmission 54 and transconjunctival spread of COV-ID-19 55 . The operative microscope offers protection for the eyes of surgeon, but the drilling exposes all healthcare personnel in the operating room. Otologic procedures are generally elective surgeries and should be postponed. For clinical conditions that cannot be postponed, several algorithms and classifications have been proposed to stratify otologic procedures 56 . Table III summarises the otologic and neurotologic procedures and provides a decisional algorithm.
Head and neck oncologic surgery Oncological activity is generally considered nonelective, and diagnostic or treatment procedures should be per-formed as soon as possible. Most upper aerodigestive tract malignancies grow rapidly and quickly metastasise to locoregional lymph nodes. Treatment delays of 20-30 days are often associated with tumour upstaging and worse overall survival 57 . In addition, delayed treatment can result in a more aggressive tumour resection. On the other side, otolaryngology specialists are at high risk of infection due to exposure to respiratory droplets. Furthermore, in head and neck cancers alternative treatments to surgery are lacking. For example, for cancers arising from the oral cavity or advanced laryngeal cancers or human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) or salivary gland malignancies, surgery is the main treatment and there are no accepted neoadjuvant treatment options 58 . During the first phases of the pandemic, when diagnostic tests were limited and vaccines were not available, some authors suggested to favour radiation and chemotherapy for head and neck neoplasms if oncologic outcomes were comparable to surgery 59 . For these reasons, head and neck cancer management during the COVID-19 pandemic represented a challenge for surgeons and all specialists involved in the treatment of these pathologies. To reduce the risk of missing or delayed oncological diagnosis, oncology centres began performing a selection of scheduled visits by examining the symptoms reported and previous medical history 26 . The most frequent criteria found in the literature to select patients were history of  Figure 3 shows a suggested flowchart for patient selection. Surgery can be postponed (6-8 weeks) for only a few head and neck cancer types, including well-differentiated thyroid cancers, non-progressive skin cancers (basocellular carcinoma), slow-growing salivary gland cancers and nodules in the salivary glands not classified as malignant during preoperative assessment 25 . The COVIDSurg Collaborative group 60 evaluated 1137 consecutive patients with head and neck cancer in 26 countries and reported evidence of de-escalation of surgical treatment for oropharynx and larynx tumours. For these neoplasms, nonsurgical therapy was favoured, especially during the initial phases of the pandemic. The authors concluded that an important change has come with the advent of vaccines and improvement of infection control practices and neck surgery may be considered safe for patients during the pandemic.

Conclusions
The spread of COVID-19 in the last two years has led to profound changes in the behaviour and in the organisation of healthcare systems to guarantee medical assistance. Upper airway tract symptoms (coughing and sneezing) are the most frequent route of transmission of the virus. In this context, otolaryngology activity implies a high risk of contagion during outpatient visits, surgery or urgent conditions. The correct use of PPE and a reduction of nonurgent visits and elective surgery are considered the main strategies to limit contagion. On the other hand, the fear of contagion by patients caused a delay of treatment in urgent or oncological conditions that, in some cases, may lead to a most severe clinical situation. As of today, it is impossible to predict when the COVID-19 pandemic will end; therefore, national healthcare systems worldwide should focus on strengthening medical services to also guarantee medical care for non-urgent patients, while still limiting the risk of contagion among patients and healthcare providers.

Conflict of interest statement
The authors declare no conflict of interest.

Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.