Abstract
INTRODUCTION: Patients with hematologic malignancies who undergo immunosuppressive therapies such as chimeric antigen receptor T-cell (CAR-T) therapy are at high risk of prolonged SARS-CoV-2 infection due to impaired humoral immunity. Treatment options remain limited, with variable efficacy, in such settings. METHODS: We describe a 21-year-old man with Down syndrome and B-cell acute lymphoblastic leukemia complicated by B-cell aplasia following CD19-directed CAR-T therapy. The patient developed COVID-19 and experienced persistent symptomatic infection, with high viral load and prolonged reverse transcriptase-polymerase chain reaction (RT-PCR) positivity for more than 7 months. RESULTS: Despite multiple courses of remdesivir and extended weekly infusions of COVID-19 convalescent plasma (CCP), the patient remained viremic and intermittently symptomatic. Anti-SARS-CoV-2 immunoglobulin G titers were detectable only toward the latter time frame of treatment, and passive antibody therapy with CCP was insufficient for viral clearance. Ultimately, compassionate use of monoclonal antibody (mAb) therapy (casirivimab and imdevimab) was granted. Following administration, the patient achieved viral clearance for the first time, with resolution of symptoms and persistently negative RT-PCR findings for 8 months of available follow-up thereafter. DISCUSSION: This case illustrates the limitations of CCP in patients with prolonged SARS-CoV-2 infection and highlights the effectiveness of mAbs in achieving viral clearance in severely immunocompromised hosts. It supports targeted use of mAb therapy in select high-risk populations and reinforces the importance of specific passive immunotherapy strategies (when available) for the management of viremia in immunodeficient patients.