key: cord-0702287-w5t5oxib
authors: Allisan‐Arrighi, Annie E.; Rapoport, Sarah K.; Laitman, Benjamin M.; Bahethi, Rohini; Mori, Matthew; Woo, Peak; Genden, Eric; Courey, Mark; Kirke, Diana N.
title: Long‐term upper aerodigestive sequelae as a result of infection with COVID‐19
date: 2022-03-09
journal: Laryngoscope Investig Otolaryngol
DOI: 10.1002/lio2.763
sha: 7bbb0bccff76cf2a4d8f17f62a5ca13a1c361312
doc_id: 702287
cord_uid: w5t5oxib

OBJECTIVES: Respiratory, voice, and swallowing difficulties after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) may result secondary to upper airway disease from prolonged intubation or mechanisms related to the virus itself. We examined a cohort who presented with new laryngeal complaints following documented SARS‐CoV‐2 infection. We characterized their voice, airway, and/or swallowing symptoms and reviewed the clinical course of their complaints to understand how the natural history of these symptoms relates to COVID‐19 infections. METHODS: Retrospective review of patients who presented to our department with upper aerodigestive complaints as sequelae of prior infection with, and management of, SARS‐CoV‐2. RESULTS: Eighty‐one patients met the inclusion criteria. Median age was 54.23 years (±17.36). Most common presenting symptoms were dysphonia (n = 58, 71.6%), dysphagia/odynophagia (n = 16, 19.75%), and sore throat (n = 9, 11.11%). Thirty‐one patients (38.27%) presented after intubation. Mean length of intubation was 16.85 days (range 1–35). Eighteen patients underwent tracheostomy and were decannulated after an average of 70.69 days (range 23–160). Patients with history of intubation were significantly more likely than nonintubated patients to be diagnosed with a granuloma (8 vs. 0, respectively, p < .01). Fifty patients (61.73%) were treated for SARS‐CoV‐2 without requiring intubation and were significantly more likely to be diagnosed with muscle tension dysphonia (19 vs. 1, p < .01) and laryngopharyngeal reflux (18 vs. 1, p < .01). CONCLUSION: In patients with persistent dyspnea, dysphonia, or dysphagia after recovering from SARS‐CoV‐2, early otolaryngology consultation should be considered. Accurate diagnosis and prompt management of these common underlying etiologies may improve long‐term patient outcomes. LEVEL OF EVIDENCE: 4

K E Y W O R D S airway, COVID-19, long haul, long term, SARS-CoV-2, swallow, voice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, colloquially referred to as COVID- 19) has now been demonstrated to affect all major organ systems. [1] [2] [3] [4] [5] [6] The upper respiratory tract, which is considered a unified airway with the lower respiratory tract, serves as the initial nidus for SARS-CoV-2 infections and has been welldemonstrated by the now commonly known symptoms of anosmia, hyposmia, phantosmia, and dysgeusia. [7] [8] [9] The term "long COVID" has been devised to refer to the profound, enduring effects of COVID infections on those who survive the acute, and often harrowing, stages of the disease. 10 Interestingly, in the chronic, long-haul population, evidence is mounting that patients are commonly presenting with laryngological complaints to their health care providers. 11 It is clear that a large subset of these laryngeal sequelae, including laryngotracheal stenosis, laryngomalacia, ulceration, and tracheitis, have been found to be secondary to prolonged intubations. [11] [12] [13] [14] [15] However, although these laryngotracheal sequelae are deserving of attention and analysis, 16, 17 they by no means constitute the sole laryngological consequences of SARS-CoV-2 infections. Additionally, the latter do not account for the patients who were never intubated and, in fact, may never even have sought medical care during their

infections, yet now present with new laryngological symptoms such as dysphagia, globus, and vocal fold dysfunction. 18, 19 Being in New York City (NYC), one of the original epicenters of the pandemic, provides us with the unusual privilege of obtaining a greater understanding of the breadth of SARS-CoV-2 laryngeal manifestations. This is because at the height of the first wave of the pandemic in April 2020, an estimated 1 in 20 people in NYC were infected with SARS-CoV-2, and 1 in 11 of those in the United States who contracted the illness died from their infection. 20, 21 Much of the current knowledge of the laryngeal manifestations of SARS-CoV-2 is either anecdotal or derived from individual case reports. To obtain a greater understanding of the breadth of laryngeal manifestations, our team retrospectively examined a large cohort of patients presenting with laryngeal pathologies following documented SARS-CoV-2. Since these patients were presenting after the resolution of their acute infections and with concern for subsequent sequelae of their infections, we categorized their clinical presentations under "long-term" effects of a COVID-19 infection. We characterized their new, primary presenting symptoms and then reviewed the clinical courses associated with their laryngeal complaints to gain a deeper understanding of the natural history of their symptoms as they related to their earlier SARS-CoV-2 infections. Awareness of how SARS-CoV-2 infections manifest in patients who have otherwise recovered from their infections is critical to understanding both how to treat and counsel patients.

The diagnoses and patterns of presentations here should not be dismissed as idiopathic, but rather identified by the otolaryngologist through careful history and examination among the possible ramifications of COVID-19 infections.

This study was reviewed and approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board (IRB-20-04319). 

Patient charts were examined for demographic information (age, sex, and body mass index [BMI]), presenting symptom, ultimate diagnosis, interventions (if any), and medical comorbidities. To prevent confounding or bias, any patients previously seen by laryngologists in our clinic who presented to our clinic after sustaining infections with COVID-19 were excluded from our study. Multiple presenting symptoms were recorded, if elicited. Additional key variables related to COVID-19 symptoms, complications, and treatments (e.g., intubation history, endotracheal tube size, length of intubation, tracheostomy history, and ICU length of stay) were documented to characterize the severity of infection.

Arytenoid ankylosis was often suspected based on high clinical suspicion from concern for joint fixation based on history and laryngoscopy findings, as well as CT scan findings with fine cuts through the larynx (when possible) demonstrating loss of the cricoarytenoid joint space. Palpation of the joints in the operating room confirmed fixation and immobility of the joints. Vocal fold paralysis was diagnosed when there was complete immobility of the joint and vocal fold with bowing of the cord and ipsilateral tilt of the interarytenoid cleft.

Vocal fold paresis was diagnosed when vocal fold mobility was noted to be asymmetric, with one fold hypomobile on endoscopy, and amplitude was noted to be larger on the paretic side on stroboscopy. 

There were 81 patients (49M, 32F) that met our inclusion criteria, with 31 (38.27%) of these having been intubated (see Table 1 ). These 

The overall most common presenting symptom was dysphonia (n = 58, 71.60%) in both those who had been intubated (n = 20, 64.25%) and not intubated (n = 38, 76.00%) (see Table 2 ). Certain presenting symptoms such as dysphagia, stridor, and tracheostomy dependence were more common in patients who had been intubated, however were not statistically significant on further analysis.

The patients in our cohort were diagnosed with 17 different aerodigestive diagnoses (see Table 3 ). Muscle tension dysphonia (MTD) and laryngopharyngeal reflux (LPR) were more commonly found in the group of patients that were not intubated (p < .01). Diagnoses such as granulomas, arytenoid ankylosis, posterior/subglottic stenosis (PGS/SGS), and tracheomalacia were found exclusively in intubated COVID patients; however, only granuloma was found to be statistically significant in this group (p < .01).

Vocal fold injections with either Restylane or steroids, depending on the diagnosis, were the most common procedure performed in both previously intubated (n = 6, 19.35%) and nonintubated (n = 3, 6.00%) patients (see Table 4 ). Bronchoscopy with endoscopic dilation was the second most common intervention in previously intubated patients (n = 4, 12.90%). Referral to a speech-language pathologist was the most common referral in patients without a previous intubation history (n = 4, 8.00%).

Stenotic airway lesions such as arytenoid ankylosis, SGS, PGS, and tracheal stenosis were only seen in patients with prior intubation history (see Table 5 ). Patients with arytenoid ankylosis on average were infections. None of the above characteristics were statistically significant on further analysis.

Sixteen percent of patients (n = 13) were diagnosed with either vocal fold paralysis or paresis (see Table 6 ). Vocal fold paralysis was more likely to be diagnosed in patients with a history of prior intubation.

The majority of patients in both the paresis (66.67%) and paralysis cohorts (85.71%) were male, and both groups possessed comparable BMIs (28.85 vs. 28.29, p = .16).

Diagnoses of MTD, LPR, and laryngeal hypersensitivity were more common in nonintubated post-COVID patients (see Table 7 ). 12, 17, 22, 23 The etiology of these laryngeal manifestations may be the inflammatory nature of COVID-19 infections or the intubation itself. The upper aerodigestive tract has long been considered to be part of a unified airway with the lower respiratory tract, the latter being the primary target of SARS-CoV-2. 24 It is well-known that the virus enters the cells of the respiratory tract by attaching to angiotensin converting enzyme 2 (ACE-2). 24 Current postmortem studies have mostly focused on the lower respiratory tract and why the disease causes severe lung injury and acute respiratory distress syndrome. 24, 25 However, in two autopsy cases published thus far, tracheitis has been noted with chronic inflammation and edema. 6, 24, 25 Although it is difficult to ascertain whether this highly inflammatory nature of the infection is itself the cause or the effect of the resulting intubation, it is important to note that ACE-2 receptors are also found in the upper respiratory tract, likely establishing a predisposition to causality. 6, 24, 25 Furthermore, the inherent high viral load of SARS-CoV-2 in the oro- These trends serve as noteworthy starting points to further refine our understanding of how to accurately diagnose patients based on their intubation history and presenting clinical symptoms.

Given that otolaryngologists will be grappling with the consequences of this pandemic for years to come, it is essential that they be aware of the diagnostic range of post-COVID-19 infection sequelae within the upper aerodigestive tract. 28 Moreover, it behooves otolaryngologists to understand how patient history and presenting symptoms can likely portend the patient's underlying diagnosis. Recognizing and managing these symptoms will allow otolaryngologists to reduce the burden of the sequelae from COVID-19.

Sarah K. Rapoport https://orcid.org/0000-0003-2697-8480

Rohini Bahethi https://orcid.org/0000-0002-7041-5346

Peak Woo https://orcid.org/0000-0003-0144-5178

Mark Courey https://orcid.org/0000-0001-6885-2929

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