Adverse Reaction to Tixagevimab and Cilgavimab (Evusheld): Anaphylaxis or Not?

Introduction: Tixagevimab and cilgavimab (Evusheld) are long-acting monoclonal antibodies indicated for COVID-19 pre-exposure prophylaxis. Although multiple endotypes of hypersensitivity reactions to monoclonal antibodies have been described, including type I (IgE and non-IgE-mediated) reactions, cytokine release, mixed reactions, and type IV delayed reactions, serious hypersensitivity reactions to Evusheld are rare. We present a case of Evusheld adverse reaction, potentially consistent with anaphylaxis. Case Description: 72-year-old female with Sjogren's syndrome, rheumatoid arthritis, secondary hypogammaglobulinemia from rituximab, interstitial lung disease, and laryngospasm received intramuscular Evusheld in clinic. Forty minutes later, the patient developed throat pain, throat fullness, difficulty swallowing, and dyspnea without wheezing or hypoxia. Documentation noted an unspecified rash. Vitals were stable. The patient was administered epinephrine, diphenhydramine, and steroids and transferred to the emergency department where symptoms resolved. However, five hours later, she developed recurrent throat fullness and difficulty swallowing, resulting in repeat Epinephrine. Flexible laryngoscopy was unremarkable. She had two additional self-resolving episodes of throat tightness at 12 and 24 hours. Labs drawn 24 hours after the initial reaction demonstrated IgE <2 kU/L, tryptase <2 ug/L, and IL-6 <2 pg/mL. The patient was discharged with 5-days of antihistamines and steroids. Discussion(s): This case highlights the difficulty in diagnosing anaphylaxis. While certain features of the patient's clinical symptoms were suggestive of anaphylaxis (rash, dyspnea, and throat symptoms), her long-standing history of laryngospasm, unremarkable laryngoscopy, undetectable serum IgE, and non-elevated tryptase suggest against an immediate IgE-mediated type I hypersensitivity reaction to Evusheld. A detailed risk-benefit discussion with the patient is warranted before consideration of future Evusheld doses. Copyright © 2022

Airway Management and Otolaryngology Involvement in Pediatric Upper Respiratory Infections

Introduction: Viral upper respiratory tract infections (URTI) such as respiratory syncytial virus, rhinoenterovirus coronavirus, and others are common in children, and they can have serious effects on the pediatric airway. The literature is limited on how often ear, nose, and throat (ENT) clinician involvement is required in patients admitted with a URTI. This project aims to characterize and identify factors associated with ENT involvement in care of pediatric patients with positive respiratory virus panels (RVP) and if any require airway interventions. Method(s): A retrospective study was conducted collecting information on patient demographics, comorbidities, course of treatment, incidence of ENT consultation, and incidence of airway interventions (flexible laryngoscopy, intubation, tracheostomy, direct laryngoscopy, etc) for all pediatric patients with a positive RVP who were treated either inpatient or in the emergency department from January 2018 to January 2020 at a tertiary care academic facility. Result(s): A total of 1019 of 1317 consecutive charts with a positive RVP over a 2-year period were reviewed. Preliminary result analysis was completed for the 1019 completed charts. Twenty-eight patients (2.7%) required an ENT consultation. Congenital birth defects were significantly associated with ENT consultation (odds ratio [OR]=3.75;P=.001). Length of stay was significantly associated with higher rate of ENT consultation per day of stay (OR=1.07 per day of stay;P<.001). All other factors studied were not significantly associated with higher rate of ENT consult. Conclusion(s): The incidence of ENT consultation in inpatients with URTIs is relatively uncommon. The preliminary data of this study suggest congenital birth defects and longer length of stay could be used as potential markers to help identify patients who may be at increased risk for worse airway outcomes and need for further airway intervention.

Using Extracorporeal Membrane Oxygenation for COVID-Positive Urgent Tracheostomy

Introduction: Extracorporeal membrane oxygenation (ECMO) can be used during difficult airway surgery because it provides an unobstructed operative field while ensuring adequate oxygenation without need for ventilation. We present a case of utilizing ECMO to perform urgent tracheostomy on a COVIDpositive patient with a large oropharyngeal mass causing critical airway narrowing. Method(s): A 62-year-old man presented with 6 months of worsening dyspnea. Computed tomography imaging and flexible laryngoscopy showed a large oropharyngeal mass extending into the nasopharynx and larynx causing critical airway narrowing and severely distorted upper airway anatomy. Traditional methods to secure the airway including transnasal vs transoral intubation vs awake tracheostomy were considered inadequate due to tumor location/friability, trismus, inability to lie flat, and unclear tracheal landmarks on palpation. In addition, on the day of surgery, the patient tested positive for COVID. We decided ECMO was the safest method to safely perform tracheostomy while minimizing COVID aerosolization. Result(s): The thoracic surgery team proceeded with bifemoral cannulation, and ECMO was initiated in less than 30 minutes. Standard tracheostomy was performed, and biopsies of the oropharyngeal mass were obtained. The patient was weaned off ECMO after <1 hour and awakened without any issues. There were no complications from bi-femoral venous access. Conclusion(s): Multiple methods to secure this patient's difficult airway were considered. Fiber-optic nasal intubation would require navigating the bronchoscope around the large tumor partially obstructing the nasopharynx and larynx. Awake tracheostomy was considered risky due to his large neck circumference, significant coughing episodes, and inability to lay supine. Both of these options would also be associated with high levels of COVID aerosolization. The use of ECMO allowed for apneic tracheostomy while minimizing the risk of COVID infection to all operating room personnel. In the era of COVID, ECMO is an unconventional but powerful tool that should be added to the armamentarium of highrisk airway surgery.

Effect of COVID-19 on the Incidence of Postintubation Laryngeal Lesions

Introduction: Critically ill patients intubated in the intensive care unit experience prolonged intubation leading to increased frequency of laryngeal injuries, and there is an increasing need for intubation and mechanical ventilation currently due to the COVID-19 pandemic. It is important to fill the literature gaps regarding the incidence of laryngeal injury following prolonged intubation due to COVID-19. Method(s): This study is a retrospective review of patients with swallowing, voice, or airway concerns identified by their primary physician or speech-language pathologist who were evaluated using flexible laryngoscopy from August 14, 2020, to August 18, 2021. A total of 25 patients with COVID-19 and 27 patients without COVID-19 were included. Specific injuries evaluated for were edema/erythema, granulation tissue/ ulceration, posterior glottic stenosis, subglottic stenosis, vocal cord immobility, and vocal cord paralysis. Severe lesions were those that caused significant airway obstruction or required operative treatment or tracheostomy dependence. Result(s): Within the COVID-19 group, 80% of patients had laryngeal injury, with 45% of these in the severe category. In the non-COVID-19 group, 62.9% of patients had a laryngeal injury, with 23.5% being severe. Mild injuries were seen in 44% of COVID-19 patients and 48% of non-COVID-19 patients. The most common injury category seen was granulation tissue/ulceration. Patients with severe injuries were intubated for 6 to 39 days (mean 14.8), those with mild injuries were intubated for 0 to 31 days (mean 10.4), and patients with no injuries were intubated for 0 to 34 days (mean 9.53). Conclusion(s): Patients who were intubated for COVID-19 were more likely to have severe clinically significant laryngeal injuries than non-COVID-19 patients, even when they were intubated for similar amounts of time. Interestingly, the incidence of mild injuries was similar between the 2 groups. Based on these results, it may be beneficial to have a lower threshold for performing flexible laryngoscopy on postintubated COVID-19 patients to evaluate for laryngeal injury. This would allow for earlier intervention and, it is hoped, reduction of morbidity.

REACTIVE INFECTIOUS MUCOCUTANEOUS ERUPTION (RIME) THROUGH REASON: EVALUATING ORAL SWELLING IN A PATIENT WITH COVID-19

CASE: A 22-year-old woman with h/o asthma initially presented to the hospital with lip swelling and sore throat. She tested positive for COVID-19 and received a casirivimab-imdevimab (monoclonal antibody) infusion. She returned a week later with worsening lip swelling, dysphagia and conjunctivitis. Physical exam revealed edematous lips with vesicular lesions, no tongue swelling, tonsillar exudate, 4+ conjunctival injection bilaterally with purulent discharge, and shallow clean based clitoral ulceration. She reports no history of allergic reactions, angioedema or exposure to new medications. Nasopharyngolaryngoscopy showed no laryngeal edema but visualized exudates throughout the supraglottis and glottis. C4, ANA, CMV, EBV, throat and blood cultures were negative. STI testing was trichomonas positive and gonorrhea/chlamydia negative. Respiratory virus panel remained positive for COVID-19. HSV swab of lip lesion, HSV 1/2 IgG and IgM were negative. Mycoplasma pneumoniae IgG was elevated (0.60, negative is ≤0.09), IgM equivocal (0.85, negative is ≤0.76), and nasopharyngeal PCR negative. Conjunctival culture showed rare bacteria (S. Aureus) and no leukocytes. She initially received methylprednisolone IV due to concern for angioedema, acyclovir for empiric HSV treatment and empiric antibacterial moxifloxacin eye drops. Given lack of infectious trigger, her presentation was concerning for reactive infectious mucocutaneous eruption (RIME) associated with SARSCoV-2 or Mycoplasma. Prednisone 1mg/kg daily was initiated followed by improvement in oral mucositis and conjunctivitis within days. IMPACT/DISCUSSION: A broad differential is important when evaluating oral swelling and mucositis. Her lack of cutaneous involvement, medication exposure or family history and negative infectious, autoimmune and inflammatory workup make other causes including Stevens-Johnson syndrome, erythema multiforme, angioedema, and HSV less likely. Our final diagnosis of RIME describes mucocutaneous eruptions likely due to an immune response triggered by bacterial or viral infection. Our patient's RIME may be due to COVID-19 or Mycoplasma given her equivocal Mycoplasma IgM. Eruptions generally involve two or more mucosal sites and occur mostly in children and adolescents. Common presentations include oral erosions and ulcers, purulent bilateral conjunctivitis, or urogenital lesions, which were all seen in our patient. As this is a relatively rare and new condition, no standard of care treatment exists for RIME but systemic steroids have been effective in case reports for initial treatment and subsequent flares. CONCLUSION: RIME is a rare, newly described condition in young patients who develop postinfectious mucocutaneous eruptions of two or more mucosal sites. It has been recently reported in association with COVID-19 and its association with Mycoplasma infection is important to evaluate. This condition is important to recognize and treat given the requirement for higher dose steroids than that used for angioedema.

SARS COV-2 AS A RISK FOR ANGIOEDEMA

CASE: This is a 41-year-old man who was admitted to the medical floor with mild COVID-19 symptoms without hypoxia. He had End Stage Renal Disease (ESRD) on Hemodialysis (HD), failed renal transplant, Hypertension and Schizophrenia. Patient had no relevant family history. Medications included Aspirin, Atorvastatin, Nifedipine, Benztropine, and Haloperidol. Patient had allergy to shellfish products. He tested positive a week prior to admission with mild cough no fever or hypoxia. As symptoms worsened, he presented to emergency department and was admitted because of his immunocompromised status. The night of admission, he developed wheezing and stridor, swelling of face and lips, and altered mental status. It was difficult to pass endotracheal tube due to swollen airways. Vital signs were stable except for a low oxygen saturation. Physical examination significant for stridor and swelling of the face and lips. Laboratory values were not significant. We reviewed and none of them was newly started or associated with risks of angioedema. He had no history of previous similar episodes. Patient was given anti-histamines and steroids with slight improvement. Flexible laryngoscopy was performed showing swollen epiglottis and aryepiglottic folds. He ended up getting a tracheostomy as he was regarded as a high risk to be liberated from intubation. IMPACT/DISCUSSION: Few other cases of COVID-associated angioedema have been reported in the literature, majority of the cases explained were in African American patients. The features of angioedema reported like the traditional angioedema, swelling of the face, lips and airways. This angioedema developed within 7 days of detection of COVID-19 in our case and >10 days in the previously reported cases. Angioedema develops due to increased levels of Bradykinin (BK) and its metabolites due to increased expression or decreased degradation. Angiotensin Converting Enzyme (ACE) with other enzymes prevent angioedema by degradation of BK and its metabolites . African Americans, have genetic susceptibility which leads to lower levels of other enzymes involved in the Bradykinin metabolism, thus ACE blockade put them at a higher risk of angioedema. The association of COVID-19 with ACE2 and its subsequent disruption of ACE activity is thought to be the reason behind the development of angioedema. Most of the published articles are either observational or sporadic case reports. More thorough study might help identify further mechanisms and if there is a direct true causal relationship between COVID-19 infection and angioedema or if it is the result of a “second hit,” as it was called by authors of another case that involved a Caucasian male with hypertension who has been using Lisinopril for years with no previously reported complaint. CONCLUSION: SARS CoV-2 should be suspected as cause for angioedema. Further studies needed to establish modalities for diagnosis, management and prevention in high-risk patients.

A Rare Cause of Angioedema - A Novel Case Report

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well described as an etiology to severe acute respiratory distress syndrome (ARDS). However, rare immunologic and allergic manifestations may also occur from this infection. We report a novel case of angioedema occurring in the setting of COVID-19 infection in a fully vaccinated patient. Case Report: A 61-yearold COVID-19 vaccinated female with hypertension presented to the emergency department with tongue and lip swelling, odynophagia, dysphonia, and difficulty breathing. She denied personal or family history of allergies, anaphylaxis, or angioedema. Her home medications included Aspirin, methadone, Seroquel, and Klonopin, with no recent changes reported. Physical exam was notable for significant lip and tongue edema, audible dysphonia, and bilateral end-inspiratory wheezing. She was hypoxemic and placed on nasal cannula. Laboratory findings revealed lymphopenia, elevated inflammatory proteins, including C-reactive protein (57), Lactate dehydrogenase (LDH) (238), and D-dimer (11.52). Functional C1 esterase inhibitor levels (>91) were normal. Nasal PCR swab returned positive for SARS-CoV-2. Ear, nose, and throat specialist was consulted given concern for angioedema, and flexible nasolaryngoscopy was performed revealing uvular, epiglottic, and bilateral arytenoid edema concerning for impending airway compromise. The patient was initiated on intravenous methylprednisolone, epinephrine, antihistamines, tranexamic acid and admitted to the medical intensive care unit (ICU). She was monitored closely in the ICU with subsequent improvement of the angioedema and resolution of the hypoxemia. She was discharged with an oral steroid regimen and scheduled for a follow-up appointment with an allergist. Discussion: There exists only a handful of case reports describing angioedema in patients with COVID-19 infection. In those reports, patients also had normal C1 esterase inhibitor levels and no personal or family history of inherited angioedema. Interestingly, our patient was vaccinated six months prior to her presentation. The association between SARS-CoV-2 and angiotensinconverting enzyme 2 (ACE-2), the primary receptor for viral entry into the epithelial cells of the lungs, could be a potential explanation for the occurrence of angioedema. ACE-2 plays a pivotal role in inhibiting a potent ligand of bradykinin receptor 1, Arginine bradykinin. It has been postulated that SARS-CoV-2 downregulation of ACE-2 leads to elevated angiotensin II levels and subsequent activation of the bradykinin pathway. Excessive bradykinin production generates high levels of nitric oxide and prostaglandins, resulting in vasodilation, increased vascular permeability, and angioedema. This case highlights the importance of recognizing atypical and rare presentations of COVID-19 infection, especially angioedema, given its sudden onset and life-threatening complications.

Quantification and visualization of aerosols in ear, nose, and throat exam and flexible laryngoscopy.

Objective: To measure and visualize aerosol generation during ear, nose, and throat (ENT) exam and flexible laryngoscopy, as safety recommendations are currently to defer routine and low-priority examinations. Methods: Aerosols generated during ENT examination and flexible laryngoscopy were quantified by laser aerosol spectrometry and visualized live by high-speed imaging during those procedures for three participants who were tested three times for each test. Results: Routine ENT examination and flexible laryngoscopy produce aerosols at levels comparable to normal breathing and speech. Conclusion: During ENT examination and flexible laryngoscopy, the practitioner should wear a surgical mask and potentially contaminated surfaces should be cleaned after the procedure. For flexible laryngoscopy, it is recommended in addition that the patient wear a mask over the mouth in case the procedure induces a sneeze. The time during which the patient is unmasked should be minimized. In these settings, the risk to the practitioner is minimal unless the patient is sneezing or symptomatic. Level of Evidence: 1.

RESPIRATORY DISTRESS IN A NEONATE - WHEN BOARDS MEET REAL LIFE

Case Report A male infant is born at 37w to a 34-year-old G3P2 mother by vaginal delivery after an uncomplicated pregnancy. Prenatal screens are negative. The patient had a birth weight of 2,620 g, with Apgar scores of 9 and 9. On day 2 after birth, had increased work of breathing which prompted transfer to a level II NICU for further management. On arrival to the unit, the infant is tachypneic with mild chest wall retractions and thick nasal secretions. A CBC and blood culture were collected and empiric antibiotic therapy was started. Respiratory viral panel and COVID test are negative. A chest radiograph shows a middle lobe opacity concerning for pneumonia (figure 1). His clinical status failed to improve and on day 4 after birth, supplemental oxygen was provided. The primary team consulted ENT and Pulmonology services. Flexible laryngoscopy showed a normal anatomy. Pulmonology recommended transferring to our NICU for a chest CT with bronchoscopy. Our differential diagnosis for this neonate with respiratory distress that fails to improve over time or with antibiotics was broad, but further testing revealed this infant's condition. A CBC, CRP and a blood gas were collected on admission and were normal. ID service was consulted. A Chest CT showed bilateral atelectasis. Bronchoscopy showed a normal anatomy. Bronchoalveolar lavage was sent. Umbilicus swab was positive for MRSA, nasal wash/sputum culture/bronchoalveolar fluid also grew moderate S. aureus. Nasal ciliary biopsy sent for electron microscopy. Positive umbilicus and nasal swab, and subsequently BAL for MRSA led to a diagnosis of MRSA neonatal rhinitis. Therapy with IV vancomycin was initiated and later changed to oral clindamycin to complete a total of 14 days of therapy. The neonate was weaned off oxygen support on day 11. His clinical symptoms improved. He was discharged on oral clindamycin with follow up appointments with pulmonology and ID clinics. His ciliary biopsy showed absence of outer and inner dynein arms, compatible with the diagnosis of primary ciliary dyskinesia (PCD) (figure 2). Genetic testing for PCD showed mutations in the DNAAF1 and CCDC40 genes. This neonate was diagnosed with primary ciliary dyskinesia (PCD) but his presentation at birth was nonspecific and the differential diagnosis was broad. There is no gold standard diagnostic test for PCD and high clinical suspicion is important. Since it is most likely an AR inheritance, screening of family members is essential. Initial management of neonates may include measures that manage the respiratory distress, airway clearance to prevent respiratory infections and treat bacterial infections. Chest physiotherapy may help if recurrent atelectasis. Flexible bronchoscopy and bronchoalveolar lavage may help both to diagnose and treat the underlying infection. Antibiotic therapy based on organism growth for exacerbations may prevent development of bronchiectasis. (Figure Presented).

Audit of flexible laryngoscopy use and decontamination using a chlorine dioxide wipe system during COVID-19: Assessing the risk of disease transmission.

Aim: To assess the efficiency of decontamination of flexible nasoendoscopes using a chlorine dioxide wipe system and assessing the risk of disease transmission during the COVID-19 pandemic. Method: Prospective and retrospective review of 544 patient episodes of nasoendoscopy and a study of 41 patient procedures and 22 members of staff at an ENT Outpatient Department from September 2020 to March 2021. Results: Among 41 randomly selected episodes of nasoendoscopy in the clinic, there was 93%-100% compliance with decontamination guidelines suggested by ENT UK. Among 544 patients who had nasoendoscopies, 20 had RT-PCR tests within two weeks and all yielded a negative result; no clusters of consecutive endoscopies were noted. None among the 22 clinic staff had symptoms of COVID-19 infection during the study period. Conclusion: Accepting the limitations of the study design, this audit found no evidence of nosocomial transmission of SARS-CoV-2 virus related to use or reprocessing of flexible nasoendoscopes among patients and staff following good compliance to ENT UK decontamination guidelines.

Is Office Laryngoscopy an Aerosol-Generating Procedure?

OBJECTIVES/HYPOTHESIS: The aims of this work were 1) to investigate whether office laryngoscopy is an aerosol-generating procedure with an optical particle sizer (OPS) during clinical simulation on healthy volunteers, and 2) to critically discuss methods for assessment of aerosolizing potentials in invasive interventions. STUDY DESIGN: Prospective quantification of aerosol and droplet generation during clinical simulation of rigid and flexible laryngoscopy. METHODS: Two healthy volunteers were recruited to undergo both flexible and rigid laryngoscopy. An OPS was used to quantify aerosols and droplets generated for four positive controls relative to ambient particles (speech, breathing, /e/ phonation, and /ae/ phonation) and for five test interventions relative to breathing and phonation (flexible laryngoscopy, flexible laryngoscopy with humming, flexible laryngoscopy with /e/ phonation, rigid laryngoscopy, and rigid laryngoscopy with /ae/ phonation). Particle counts in mean diameter size range from 0.3 to >10 µm were measured with OPS placed at 12 cm from the subject's nose/mouth. RESULTS: None of the laryngoscopy interventions (n = 10 each) generated aerosols above that produced by breathing or phonation. Breathing (n = 40, 1-3 µm, P = .016) and /ae/ phonation (n = 10, 1-3 µm, P = .022; 3-5 µm. P = .083; >5 µm, P = .012) were statistically significant producers of aerosols and droplets. Neither speech nor /e/ phonation (n = 10 each) were associated with statistically significant aerosols and droplet generation. CONCLUSIONS: Using OPS to detect droplets and aerosols, we found that office laryngoscopy is likely not an aerosol-generating procedure. Despite its prior use in otolaryngological literature, an OPS has intrinsic limitations. Our study should be complemented with more sophisticated methods of droplet distribution measurement. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:2637-2642, 2020.