Abstract Background Epstein-Barr virus (EBV), is a double-stranded DNA virus discovered in 1964, that primarily infects B lymphocytes and is commonly associated with infectious mononucleosis, typically a benign and self-limited illness. In rare cases, it can lead to severe critical illness involving multi-systemic complications such as mixed autoimmune hemolytic anemia (AIHA). AIHA occurs in approximately 1-3% of hospitalized patients with EBV infection, though mixed AIHA (both warm and cold autoantibodies) remains exceedingly uncommon, particularly in immunocompromised individuals. Case Presentation We present the case of a 62-year-old male with HIV infection, compliant with highly active antiretroviral therapy (elvitegravir, cobicistat, emtricitabine, tenofovir), who presented with a two-week history of nonproductive cough, pleuritic chest pain, progressive dyspnea, and dark urine. On admission, he was febrile, tachycardic, tachypneic, and hypoxemic with oxygen saturation of 85% on room air. Physical exam revealed pallor, mild scleral icterus, and posterior cervical lymphadenopathy. Initial labs demonstrated severe anemia Hb 6.9 g/dL, baseline 11g/dL (normal 14-18 g/dL), creatinine 2.7 mg/dL, baseline 1.1 mg/dL (normal 0.6-1.3 mg/dL), hyperbilirubinemia 7.8 mg/dL (normal 0.3-1.0 mg/dL), LDH 724 U/L (normal 135-225 U/L), and markedly reduced haptoglobin (10 mg/dL). Urinalysis showed hemoglobinuria without RBCs. Direct Coombs test, both warm and cold autoantibody screens were positive, confirming mixed AIHA. The hospital course was complicated by worsening hemolysis necessitating multiple transfusions, acute respiratory insufficiency, and progressive acute kidney injury. Multidisciplinary consultation involving infectious disease, hematology and nephrology was done. EBV PCR returned positive. Complement C4 was reduced and C3 was normal, which was consistent with viral-associated immune dysregulation. Notably, the patient had no prior transfusion history but had multiple autoantibodies in his blood. He was treated with IV methylprednisolone for three weeks, resulting in clinical improvement: hemoglobin stabilized, renal function normalized, and oxygen supplementation was discontinued. Discussion While EBV typically manifests as a self-limiting viral syndrome, it can precipitate life-threatening complications such as mixed AIHA, especially in immunocompromised hosts. This case highlights the diagnostic challenges and severity of EBV-induced hemolysis, which can progress to multi-organ involvement requiring intensive care admission, aggressive supportive care and immunosuppressive therapies. Early recognition of EBV associated autoimmune dysregulation and prompt multidisciplinary management are critical in optimizing outcomes. Conclusion This case underscores the need for heightened vigilance when evaluating immunocompromised adults with EBV infection. EBV-induced mixed AIHA, though rare, can lead to severe respiratory failure, kidney injury, and transfusion-dependent anemia. Awareness of these complications may aid in timely diagnosis, appropriate immunomodulatory therapy, and improved survival. This abstract is funded by: None
Mbome et al. (2026) studied this question.