Abstract
Persistent fever and pulmonary infiltrates in immunocompromised patients pose a major diagnostic challenge, especially in those receiving anti-CD20 therapy that impairs humoral immunity. We present a 66-year-old man with non-Hodgkin lymphoma on obinutuzumab and lenalidomide who developed prolonged fever, dry cough, and bilateral ground-glass opacities after COVID-19 infection. The differential diagnosis included persistent viral pneumonitis, post-COVID organizing pneumonia, drug-induced lung injury, opportunistic infection, and lymphoma progression. Initial corticosteroid therapy for suspected organizing pneumonia led to partial improvement, but symptoms relapsed during tapering. Bronchoscopy and laboratory analysis confirmed invasive pulmonary aspergillosis and profound hypogammaglobulinemia, while persistent SARS-CoV-2 PCR positivity suggested impaired viral clearance due to B-cell depletion. Treatment with isavuconazole, broad-spectrum antibiotics, corticosteroids, and intravenous immunoglobulin resulted in clinical, radiological, and immunological recovery. This case highlights the importance of maintaining a broad differential diagnosis in immunocompromised patients with unresolved post-COVID pulmonary symptoms and demonstrates that prompt recognition of hypogammaglobulinemia and timely immunoglobulin replacement can be pivotal for recovery.