Severe TRALI Following Postvaccination MIS-C in a Young Female

To the Editors: We report a case of transfusion-related acute lung injury (TRALI) following intravenous immunoglobulin (IVIG) administration in an 11-year-old female with post-COVID-19 vaccination multisystem inflammatory syndrome in children (MIS-C). A previously healthy 11-year-old female presented to our pediatric intensive care unit 4 days after receiving her second COVID-19 vaccine dose (BNT162b2). She developed high fever (40 °C) unresponsive to antipyretics on day 2 postvaccination, followed by a widespread maculopapular rash involving trunk, limbs, palms, and soles. Laboratory findings revealed markedly elevated inflammatory markers: C-reactive protein 200 mg/L (normal <5), procalcitonin >20 ng/mL (normal <0.5) and interleukin-6 >200 pg/mL. Initial chest radiograph was normal. Echocardiography demonstrated moderate myocardial dysfunction with left ventricular ejection fraction of 47% and mild mitral-tricuspid regurgitation. SARS-CoV-2 reverse transcription-polymerase chain reaction and antinucleocapsid antibodies were negative, confirming no prior infection. Given the temporal relationship with vaccination, absence of prior SARS-CoV-2 infection, and fulfillment of centers for disease control and prevention criteria for MIS-C1, a diagnosis of MIS-C was established. While the association between COVID-19 vaccination and MIS-C remains under investigation and most reported cases occur several weeks after vaccination2, the temporal proximity in our case was suggestive, though not conclusive of a causal relationship. Treatment with intravenous methylprednisolone (2 mg/kg/day) and IVIG (2 g/kg) was initiated. During IVIG infusion, the patient developed acute respiratory deterioration despite high-flow nasal cannula and helmet continuous positive airway pressure support. Within 6 hours, oxygen requirements increased to FiO2 0.80. Chest radiograph revealed bilateral diffuse interstitial infiltrates consistent with acute lung injury (Fig. 1). Due to progressive respiratory failure, intubation and mechanical ventilation were required.FIGURE 1.: Chest radiograph demonstrating bilateral diffuse interstitial infiltrates consistent with TRALI, obtained 6 hours after IVIG infusion.The acute onset of respiratory distress within 6 hours of IVIG administration, bilateral pulmonary infiltrates on imaging, severe hypoxemia (PaO2/FiO2 <200), and absence of cardiac failure or fluid overload fulfilled diagnostic criteria for TRALI.3 Methylprednisolone dose was increased to 10 mg/kg/day and high-dose intravenous vitamin C (100 mg/kg/day) was administered. The rationale for vitamin C administration was based on emerging evidence suggesting potential benefit in TRALI management through reduction of inflammatory surge and capillary protection effects, as reported in the ASTRALI trial.4 Additional evidence supports vitamin C's role in reducing mortality in critically ill patients with severe pneumonia and other lung inflammatory conditions.5 The patient responded favorably, with successful extubation after 48 hours. Follow-up echocardiography showed improved cardiac function (left ventricular ejection fraction: 55%) with persistent mild valvular insufficiencies. She was discharged after 10 days with complete clinical recovery. TRALI is a serious transfusion-related complication with mortality rates of 5–25%, manifesting as acute respiratory distress and noncardiogenic pulmonary edema within 6 hours of blood product transfusion.5 While TRALI following IVIG is rare, it should be considered in patients developing acute respiratory deterioration during or shortly after infusion. The pathophysiology likely involves antibody-mediated neutrophil activation leading to endothelial damage and capillary leak syndrome6. This case highlights two important considerations: (1) the recognition of MIS-C occurring in temporal association with COVID-19 vaccination as a rare but serious adverse event requiring prompt treatment7, acknowledging that the causal relationship requires further investigation, and (2) the potential for TRALI as a life-threatening complication of IVIG therapy in MIS-C patients. Clinicians should maintain high vigilance for respiratory deterioration during IVIG administration, particularly in patients with hyperinflammatory states. Acknowledgments The authors thank the nursing staff of the Pediatric ICU for their dedicated care of this patient.