C41-25 Breaking Through the Blockade: Post-Covid EGPA in a Patient on Benralizumab

Introduction Following SARS-CoV-2 infection, an elderly woman developed altered mental status, flaccid paralysis, cardiomegaly, and marked eosinophilia, ultimately leading to the diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA). Case Presentation An 80-year-old woman with chronic rhinosinusitis with nasal polyposis (CRS-NP), severe type 2 (T2)-high asthma, and mild bronchiectasis with Mycobacterium avium-intracellulare colonization was on benralizumab therapy every two months for five years. Despite persistent sinonasal congestion requiring multiple sinus surgeries, her baseline eosinophil count remained undetectable. After a mild COVID-19 infection treated with nirmatrelvir/ritonavir (Paxlovid), she developed progressive dyspnea, fatigue, bilateral hand numbness, and generalized weakness within 11 days. On presentation, she exhibited decreased mentation, flaccid paralysis, and ecchymoses on both legs. Labs revealed troponin 7,500 ng/L, WBC 18.7 × 10³/µL, eosinophils 50% (absolute 9.6 × 10³/µL). Echocardiography showed a small pericardial effusion, EF 45%, and regional wall motion abnormalities. Brain CT demonstrated bilateral acute ischemic strokes. Infectious and hematologic evaluations were unrevealing, negative for strongyloides, HIV, syphilis, ANCA, and malignancy. Skin biopsy confirmed ecchymosis without vasculitis. The combination of eosinophilia, cardiac involvement, neurologic findings, and absence of secondary causes supported a diagnosis of EGPA. She received pulse-dose corticosteroids followed by taper and rituximab, with subsequent improvement in mentation and normalization of eosinophil counts. Discussion This case illustrates breakthrough EGPA in a patient with T2-high asthma and CRS-NP on long-term benralizumab, following SARS-CoV-2 infection. EGPA typically progresses through prodromal, eosinophilic, and vasculitic phases. Despite IL-5 receptor blockade, the patient developed marked eosinophilia and multi-organ involvement consistent with the eosinophilic and vasculitic phases. Potential mechanisms include COVID-related immune dysregulation overcoming benralizumab suppression through IL-10 or IL-13 upregulation, promoting eosinophil proliferation and activation. Paxlovid-related immune modulation may have contributed as well. The neurologic deficits (bilateral strokes) may reflect eosinophilic vasculitis or COVID-associated hypercoagulability. Conclusions EGPA can emerge or flare despite IL-5 pathway inhibition in the setting of immune perturbation from SARS-CoV-2 infection. Clinicians should maintain vigilance for breakthrough eosinophilia and vasculitic manifestations in patients with CRS-NP and asthma on benralizumab who develop new systemic or neurologic symptoms after viral infection. Early recognition and immunosuppressive therapy remain critical for recovery and prevention of irreversible organ damage. This abstract is funded by: None