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

ABSTRACT

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