key: cord-0998268-kkmcdvfh
authors: Naunheim, Matthew R.; Zhou, Allen S.; Puka, Elefteria; Franco, Ramon A.; Carroll, Thomas L.; Teng, Stephanie E.; Mallur, Pavan S.; Song, Phillip C.
title: Laryngeal complications of COVID‐19
date: 2020-10-30
journal: Laryngoscope Investig Otolaryngol
DOI: 10.1002/lio2.484
sha: bb6c9dce3ab2324ac15f141347477e2d9cf1b490
doc_id: 998268
cord_uid: kkmcdvfh

OBJECTIVE: To describe and visually depict laryngeal complications in patients recovering from coronavirus disease 2019 (COVID‐19) infection along with associated patient characteristics. STUDY DESIGN: Prospective patient series. SETTING: Tertiary laryngology care centers. SUBJECTS AND METHODS: Twenty consecutive patients aged 18 years or older presenting with laryngological complaints following recent COVID‐19 infection were included. Patient demographics, comorbid medical conditions, COVID‐19 diagnosis dates, symptoms, intubation, and tracheostomy status, along with subsequent laryngological symptoms related to voice, airway, and swallowing were collected. Findings on laryngoscopy and stroboscopy were included, if performed. RESULTS: Of the 20 patients enrolled, 65% had been intubated for an average duration of 21.8 days and 69.2% requiring prone‐position mechanical ventilation. Voice‐related complaints were the most common presenting symptom, followed by those related to swallowing and breathing. All patients who underwent flexible laryngoscopy demonstrated laryngeal abnormalities, most frequently in the glottis (93.8%), and those who underwent stroboscopy had abnormalities in mucosal wave (87.5%), periodicity (75%), closure (50%), and symmetry (50%). Unilateral vocal fold immobility was the most common diagnosis (40%), along with posterior glottic (15%) and subglottic (10%) stenoses. 45% of patients underwent further procedural intervention in the operating room or office. Many findings were suggestive of intubation‐related injury. CONCLUSION: Prolonged intubation with prone‐positioning commonly employed in COVID‐19 respiratory failure can lead to significant laryngeal complications with associated difficulties in voice, airway, and swallowing. The high percentage of glottic injuries underscores the importance of stroboscopic examination. Otolaryngologists must be prepared to manage these complications in patients recovering from COVID‐19. LEVEL OF EVIDENCE: IV.

injuries underscores the importance of stroboscopic examination. Otolaryngologists must be prepared to manage these complications in patients recovering from COVID-19.

Level of evidence: IV.

COVID-19, intubation, laryngology, larynx, stenosis, voice

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has upended the world of otolaryngology. In only a few months, it has changed the way otolaryngologists think about how we protect ourselves in the office and operating room, [1] [2] [3] [4] [5] [6] how we think about aerosolizing procedures, [7] [8] [9] [10] [11] [12] and how we participate in telemedicine. [13] [14] [15] [16] [17] Several aspects of the pandemic affect otolaryngologists in particular. As surgeons of the head and neck, tracheostomy management, anosmia evaluation, and evaluation of upper respiratory tract symptoms fall under the otolaryngologist's purview. An emerging role for otolaryngologists in the coming weeks and months is the management of laryngeal complications of COVID-19. 18 Respiratory failure requiring intubation is a common consequence of severe COVID-19 infection, 19 and laryngeal complications including damage to the vocal cords, granulomas, laryngotracheal stenosis, and swallowing impairment are wellknown sequelae of intubation. [20] [21] [22] [23] [24] [25] [26] [27] Due to concerns for high patient mortality and virus aerosolization, treatment paradigms often involve deferring tracheostomy in favor of intubation for greater than 2 weeks. 28 Additionally, prone positioning with mechanical ventilation is often used to improve oxygenation in this patient population. [29] [30] [31] Thus, it is presumed that there will be a high rate of laryngeal complications from prolonged intubation and tracheostomy in these patients recovering from COVID-19. However, there is little data to support this currently. Furthermore, the characteristics of patients who have survived COVID- 19 

A prospective electronic database was created using REDCap (Research Electronic Data Capture), a secure, web-based application designed to support data collection for research. 32,33 COVID-related treatment data was collected, including date of documented infection, presenting symptoms, intubation details and duration, need for proning, and tracheostomy status. Symptoms and findings related to subsequent presentation in the office or operating room were also collected, including voice, airway and swallowing complaints, as well as details of laryngoscopy and/or stroboscopy. Demographic information and comorbidity information were also collected. 

Twenty patients from participating clinical sites met criteria for inclusion in this study in June to July 2020. The mean age was 59.2 years (range 32-77 years), and 75% of patients were male (Table 1) . Patients had various comorbidities, with the most prevalent being hypertension (55%), type 2 diabetes mellitus (40%), asthma (20%), and obesity (15%). A history of smoking was present in 45% of the patients.

Of the 20 patients enrolled, 18 (90%) tested positive for COVID-19 by reverse transcriptase polymerase chain reaction (RT-PCR) testing, while one patient was positive on antibody testing ( Table 2) . One patient was diagnosed with COVID-19 with upper respiratory symptoms and pneumonia suggestive of a viral infection. The most common COVID-related symptoms experienced by these patients were shortness of breath (75%), fever (60%), cough (55%), and fatigue (45%). One patient (5%) was asymptomatic, and 15% of patients experienced loss of smell or taste.

In our consecutive patient series, 65% had been intubated, with a mean duration of 21.8 days (range, 9 to 33 days) ( Table 2 ). The median endotracheal tube size was 7.5, though the range was variable 

Voice-related complaints were most common at presentation, with 60% of patients reporting such symptoms ( Figure 1 ). Breathing (35%), swallowing (30%), globus (10%), and pain/soreness (10%) were the next most frequent complaints at presentation. Of those patients who were not intubated (n = 7), the most common presenting complaints were similar to the group as a whole (voice in 42.9%, breathing in 28.6%, globus in 28.6%, neck pain in 28.6%, and swallowing in 14.3%). Flexible laryngoscopy was performed in 80% of our patients (Table 3) , while the remaining 20% of patients were unable to undergo flexible laryngoscopy as they were seen in a telemedicine setting. All patients who underwent laryngoscopy were found to have abnormal findings, most commonly in the glottis (93.8%), trachea (43.8%), supraglottis (37.5%), and subglottis (18.8%). 40% of patients underwent stroboscopy, of which 87.5% had abnormal findings. These abnormalities were most commonly in the wave (87.5%), periodicity (75%), closure (50%), and symmetry (50%).

The most common diagnosis was unilateral vocal fold immobility, which was found in 8 patients (40%) (Table 4, Figure 2 ). Posterior glottic stenosis (15%, Figure 3 ) and subglottic stenosis (10%, Figure 4) were the next most common diagnoses, along with the presence of granulation tissue or edema on the vocal folds or around the tracheostomy tube (10%). In addition, two patients had evidence of posterior glottic diastasis (defined here as dysphonia secondary to posterior glottis tissue loss) ( Figure 4) . Patients frequently had more than one diagnosis (Figures 2-4) . Several patients had been longitudinally followed for longstanding laryngeal issues, which appeared to be unrelated to their COVID-19 infections. Of the patients who did not undergo intubation, none were found to have glottis stenosis, subglottic stenosis, or vocal fold paralysis (0.0%). Two patients had visual changes on laryngoscopy: one patient with a pre-existing subglottic stenosis was found to have subjective and objective worsening; one patient had a polymicrobial laryngitis.

Forty-five percent of patients required further procedural intervention following their office visits. 20% of patients underwent surgical intervention in the operating room, including 2 patients (10%) who underwent emergent same-day surgery due to airway concerns. One of these two patients required emergent tracheostomy and suspension microlaryngoscopy (SML) with balloon dilation, while the second 

In our multi-institutional experience, patients referred to the outpatient laryngology clinic following COVID-19 infection present most commonly with symptoms related to voice, followed by issues with breathing and swallowing. On endoscopic evaluation, abnormal findings are the rule rather than the exception: the glottis was the most frequently involved site, and the most common diagnosis was unilateral vocal fold immobility, followed by glottic and subglottic stenosis;

only patients who had been intubated had these diagnoses, as those who avoided intubation did not display any evidence of paralysis or stenosis. Stroboscopy was important, therefore, in this cohort. The majority of the patients who presented to our clinics had been intubation, regardless of the initial etiology of respiratory failure. [20] [21] [22] [23] [24] [25] [26] [27] These can have significant impact on health utilities and quality of life. [34] [35] [36] Similar to prior studies about prolonged intubation, we In prior studies, both modifiable and patient-specific factors have been found to be associated with increased risk of such complications F I G U R E 2 63-year-old male with A, unilateral vocal fold immobility, with prolapse of the arytenoid tower (white arrow) over the posterior aspect of the glottis, with vocal fold bowing and foreshortening ( gray arrow); and B, mild A-frame deformity with oblong shape to tracheal cartilage, with small amount of granulation tissue on posterior wall (asterisk). The blood (black arrow) is from the transcricothyroid injection of lidocaine to anesthetize before tracheoscopy in further localized trauma. Moreover, in our study, the median ETT size was 7.5, which is larger than the size that has been found to be associated with intubation-related laryngeal injury.

In addition, patient-specific risk factors such as comorbid conditions have been associated with increased risk for subsequent laryngotracheal injury following intubation. These factors include type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease, and smoking. [38] [39] [40] 43, 44 It is thought that these factors may predispose patients to ETT-induced mucosal injury of the larynx and impaired healing once injury occurs. 40 Several of these comorbidities have also been associated with increased severity of COVID-19 infection, 42, 45 suggesting that not only are these patients at greater risk of intubation but also at increased risk of subsequent intubation-related laryngeal sequelae. Indeed, we found high rates of type 2 diabetes mellitus, hypertension, and prior smoking history within our study sample, consistent with these prior findings. Given small numbers, tests for significance were not performed. In particular, nearly half (45%) of the patients in our sample had a significant prior smoking history. Given the known risk of smoking for lung and laryngeal health, and the modifiable nature of this risk factor, smoking should be actively discouraged in patients at high risk of contracting and having complications of COVID-19.

Management of these intubation-related injuries in COVID-19 may involve vocal fold injections for vocal fold immobility and steroid injections or resection for subglottic stenosis. Of course, tracheotomy or other urgent airway intervention (cordotomy, arytenoidectomy, dilation, or steroid injection) is sometimes necessary in these patients.

However, certain complications such as posterior glottic diastasis and related postintubation phonatory insufficiency (PIPI) can be particularly difficult to recognize and address. [46] [47] [48] There are limitations to this data. Our sample, although multiinstitutional, is small, precluding evaluation of statistical significance. COVID-19 is increasingly understood to be a systemic disease with extrapulmonary manifestations in the cardiovascular, renal, neurologic, endocrine, and gastrointestinal systems and beyond, 49 

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The authors declare no potential conflict of interest. Phillip C. Song https://orcid.org/0000-0003-0206-5441