ACUTE EPIGLOTTITIS; BREAKTHROUGH COVID-19/CONFIRMED COVID-19 INFECTION; CONFIRMED CLINICAL VACCINATION FAILURE; This spontaneous report was received from literature. This report concerned a 32 year old male of an unspecified race and ethnicity. Initial information was processed along with the additional information received on 05-SEP-2022. The objective of the study is to present Breakthrough COVID-19 infection inducing acute epiglottitis in an immunized host. The patient's height, and weight were not reported. The patient's concurrent conditions included: non smoker, and tachycardic, and other pre-existing medical conditions included: The patient was afebrile and normotensive. The patient had normal cervical range of motion, and his oropharynx appeared normal without uvular deviation. The patient was previously treated with influenza vaccine when he was 1 year 11 months old, for prophylactic vaccination. The patient received covid-19 vaccine ad26.cov2.s (suspension for injection, route of admin not reported, batch number: unknown) dose was not reported, administered on 2022 for covid-19 prophylaxis. The batch number was not reported and has been requested. No concomitant medications were reported.  On an unspecified date in 2022, 4 months after vaccination, the patient presented to the emergency department with a 1-week history of worsening congestion, sore throat, hoarse voice, odynophagia, and posterior oropharyngeal pain worse on the right than the left. The patient was seen at an outside clinic 1 day prior, where he tested negative for COVID-19 and streptococcal pharyngitis. The patient was diagnosed with acute sinusitis and given prescriptions for steroids and amoxicillin. He took these medications as prescribed but reported worsening of his symptoms on the day of presentation. His physical examination was remarkable for nasal congestion, rough voice, and tenderness to palpation of the anterior neck. His oxygen saturation of 97% on room air, but was tachycardic with a heart rate of 120 beats/min. Laboratory workup at presentation showed positivity for COVID-19 via Roche LIAT SARS assay using polymerase reaction (Confirmed clinical vaccination failure), a white blood cell count of 19.3 109/L, a C-reactive protein of 73.3 mg/dL, and a D-dimer of 0.52 mcg/mL. A respiratory virus panel was negative, and duplicate blood cultures were negative after 5 days of incubation. A radiograph and computed tomography neck soft tissue showed thickening of the epiglottis and aryepiglottic folds concerning for acute epiglottitis. The patient was treated in the emergency department with intravenous fluids, 8 mg of intravenous dexamethasone, 15 mg ketorolac, and 1 g of intravenous ceftriaxone. Flexible laryngoscopy performed in the emergency department revealed considerable edema of the epiglottis and arytenoids. The patient was treated with 10 mg intravenous dexamethasone every 8 hours for 24 hours and admitted to the hospital for observation and pain control. The number of days of hospitalization was not reported. He was discharged home the following day with instructions to complete a 7-day course of 500 mg oral amoxicillin every 8 hours and a 5-day course of 40 mg oral prednisone daily as an outpatient. The action taken with covid-19 vaccine ad26.cov2.s was not applicable. The authors emphasized that COVID-19 often leads to acute respiratory distress syndrome and that epiglottitis may cause complete upper airway obstruction, these two challenging conditions may combine into a clinically challenging multifaceted airway impairment. It is therefore necessary for the medical community to maintain a high index of clinical suspicion for epiglottitis in the setting of breakthrough SARS-CoV2 infection. The outcome of the breakthrough covid-19/confirmed covid-19 infection, confirmed clinical vaccination failure and acute epiglottitis was not reported. This report was serious (Hospitalization Caused / Prolonged). This report was associated with a product quality complaint: 90000249273.; Sender's Comments: V0: 20220900658- covid-19 vaccine ad26.cov2.s- Acute epiglottitis, Breakthrough covid-19/confirmed covid-19 infection. The event(s) has a compatible/suggestive temporal relationship, is unlabeled, and has unknown scientific plausibility. There is no information on any other factors potentially associated with the event(s). Therefore, this event(s) is considered unassessable.  20220900658-covid-19 vaccine ad26.cov2.s- Confirmed clinical vaccination failure.. The event(s) has a compatible/suggestive temporal relationship, is unlabeled, and has unknown scientific plausibility. There are other factors more likely to be associated with the event(s) than the drug. Specifically: SPECIAL SITUATIONS. Therefore, this event(s) is considered not related.