Combination Treatment of Persistent SARS-CoV-2 Infection with Dual Antiviral Therapy and Intravenous Immunoglobulin: a novel approach.

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Introduction: Immunocompromised patients, especially those with humoral immunodeficiency, face a high risk of persistent SARS-CoV-2 infection, often underdiagnosed with limited management data. Methods: Case series (Feb 2023–Sep 2024) of patients with persistent SARS-CoV-2 treated with remdesivir, nirmatrelvir/ritonavir, and IVIG. Persistent infection defined by symptoms (>21 days), consistent imaging, and persistent/intermittent RT-PCR (>21 days). A novel diagnostic/therapeutic algorithm was used (Figure 1). Results: 11 patients (55% male), median age 56 [IQR 50-66] years. 7 (64%) had hematologic malignancy (2 CLL, 5 NHL), 10 (91%) received anti-CD20 therapy (last 8 months, 8 rituximab), and 6 (55%) both. Median symptom duration 63 [58-135] days. 10 (91%) had recurrent, 1 (9%) progressive symptoms with severe respiratory failure (HFNC). 6 (55%) diagnosed via bronchoscopy (BAL). 5 (45%) required >1 and 3 (30%) >2 hospitalizations before diagnosis. Prior eradication attempts: 3 received 1 regimen with single antiviral ± immunomodulators, 2 received 2, 1 received 3, and 2 ≥4. 10 (91%) achieved complete response (follow-up 379 [215-562] days). 1 (9%) (CLL, multiple hospitalizations, 384 days post-1st positive test) died. Conclusion: Dual antiviral therapy with IVIG is a promising option for persistent COVID-19. Randomized trials are needed to determine the optimal approach. erj;66/suppl_69/PA2906/F1 F1 F1

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