Direct viral invasion and tumor-like pulmonary nodules: A fatal case of mpox in a patient with advanced HIV disease.

While mpox is typically a self-limiting zoonosis, individuals with advanced human immunodeficiency virus type 1 (HIV-1) infection are at increased risk for severe visceral complications and high mortality. We report a fatal case of fulminant mpox pneumonia in a 38-year-old male with advanced HIV-1 Infection and severe immunosuppression (CD4+ T-cell count <100 cells/µL). The patient initially presented with characteristic cutaneous lesions but rapidly progressed to dyspnea and respiratory failure. Serial chest imaging revealed diffuse, solid perivascular nodules and patchy consolidations were highly suggestive of pulmonary malignancy. While initial microbiological cultures and clinical presentation (Day 4) suggested bacterial and fungal superinfections, metagenomic next-generation sequencing (mNGS) of lung tissue biopsy identified an overwhelming burden of mpox virus (MPXV; 260,840 sequence reads), cytomegalovirus (CMV) and Epstein-Barr virus (EBV), confirming direct viral invasion of the pulmonary parenchyma. Despite comprehensive treatment with antibiotics, antifungals, CMV-targeted therapy, and mechanical ventilation (specific anti-orthopoxvirus agents were unavailable), the patient succumbed to progressive respiratory failure on Day 31. This case highlights that mpox can manifest as severe necrotizing pneumonia with tumor-like radiological features in patients with acquired immunodeficiency syndrome (AIDS). It underscores the necessity of early pulmonary imaging and molecular testing in high-risk populations to differentiate mpox pneumonia from malignancy or opportunistic infections.