Abstract Introduction Pulmonary-renal syndrome (PRS) is one of the most catastrophic complications of systemic lupus erythematosus (SLE), driven by complement-mediated endothelial injury. Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary emergency, with high mortality, characterized by bleeding into alveolar spaces from alveolar-capillary membrane disruption. DAH may be exacerbated by infections that trigger complement activation, particularly in underlying conditions such as SLE, atypical hemolytic uremic syndrome (aHUS), and thrombotic microangiopathy (TMA). We present the case of recurrent DAH secondary to complement-mediated aHUS flare triggered by coronavirus disease 2019 (COVID-19) in a patient with SLE, culminating in multi-organ failure, highlighting the challenges of managing overlapping immune dysregulation successfully treated with multimodal immunotherapy. Description A 31-year-old male with SLE complicated by Class IV lupus nephritis, TMA, and aHUS presented with acute fever, chills, and dyspnea. Upon arrival, he was in severe respiratory distress, hypoxemic (SpO2 70% on ambient air), febrile (101 °F), tachycardic (115 bpm), and hypotensive (83/61 mmHg). Point-of-care ultrasound revealed diffuse B-lines; chest radiograph showed right lower lung field haziness. Laboratory studies demonstrated acute kidney injury (creatinine 3.08 mg/dL), anemia (hemoglobin 11.8 g/dL), thrombocytopenia (platelets 72K/uL), and metabolic acidosis (pH 7.24, lactate 3.0 mmol/L). His respiratory status rapidly deteriorated requiring emergent intubation, complicated by a 4-minute pulseless electrical activity, with return of spontaneous circulation. In the intensive care unit, he developed multi-organ failure. Bronchoscopy with bronchoalveolar lavage confirmed DAH, consistent with prior episodes; this was attributed to PRS with an underlying aHUS flare exacerbating DAH. Infectious workup concurrently revealed COVID-19 pneumonia, E. coli bacteremia, and ESBL Klebsiella ventilator-associated pneumonia. He was treated with remdesivir and meropenem. Management of aHUS flare and PRS included aggressive immunomodulation: high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and eculizumab. Given history of refractory disease, additional immunosuppression with rituximab and cyclophosphamide were administered. He developed acute renal failure, requiring continuous renal replacement therapy for seven days, followed by complete renal and pulmonary recovery allowing successful extubation. Discussion What began as COVID-19 pneumonia unraveled into a deadly cascade of complement activation, endothelial injury, and diffuse hemorrhage, culminating in pulmonary-renal catastrophe. This case illustrates the challenges in managing DAH and PRS in patients with complement-mediated aHUS, where infection and immune overactivation coexist. While COVID-19 may have triggered the complement cascade, the key clinical challenge was balancing aggressive immunosuppression amid infection. Our patient’s successful recovery highlights the importance of multimodal immunotherapy and early recognition of complement dysregulation to prevent irreversible pulmonary-renal damage. This abstract is funded by: None
Shahab et al. (Fri,) studied this question.