D104-16 Adenoviral Avalanche: A Cause of Severe Primary Graft Dysfunction (pgd) After Lung Transplantation

Introduction Adenovirus typically causes mild, self-limited illness in immunocompetent hosts, but can result in severe disease in immunocompromised patients. In transplant recipients, adenovirus may be acquired via donor-derived transmission or reactivation of latent virus, with mortality rates up to 50% in solid organ recipients and higher in lung transplant populations. Therefore, early recognition and management are critical. We present a case of severe primary graft dysfunction (PGD) resulting from donor-derived adenovirus infection. Case Presentation A 67-year-old woman with scleroderma-associated interstitial lung disease and rituximab-induced hypogammaglobulinemia underwent bilateral lung transplantation. Her pre-transplantation infectious workup was unremarkable, besides a recent SARS-CoV-2 infection. She received standard induction immunosuppression and infectious prophylaxis. On postoperative day (POD) 1, she developed worsening hypoxemia, and bronchoalveolar lavage (BAL) respiratory PCR was positive for adenovirus. Plasma adenovirus viral load was 15,950 copies/mL, and immunoglobulin G (IgG) was <200 mg/dL. Despite intravenous immunoglobulin (IVIG), cidofovir, and reduction of immunosuppression, she continued to worsen to severe PGD (Figure 1), requiring cannulation for extracorporeal membrane oxygenation (VV-ECMO). Ultimately, she developed refractory multiorgan failure and shock with viral load reaching >1 million. Despite maximal supportive care, she died on POD 39. Discussion Adenovirus infection after lung transplantation is associated with high morbidity and mortality, particularly in the setting of profound immunosuppression and hypogammaglobulinemia. In this case, the early onset of infection and negative pre-transplant viral studies in the patient indicated donor-derived transmission, a recognized but less common route in lung transplant recipients. Therapeutic options for adenovirus remain limited. Cidofovir and brincidofovir are used off-label, but their effectiveness is often constrained by nephrotoxicity, which was the case for this patient. Current guidelines recommend prompt reduction of immunosuppression, initiation of antiviral therapy, and consideration of immunotherapeutic strategies, including IVIG and, in refractory cases, adoptive T-cell therapy. Another factor that complicated the patient’s course was hypogammaglobulinemia. This can result from both underlying diseases and immunosuppressive therapies, such as rituximab, which impairs humoral immunity and increases susceptibility to severe viral infections. IVIG can be administered to bolster passive immunity, but robust data supporting its efficacy for adenovirus are limited, with most evidence derived from case series and expert opinion. This case illustrates how donor-derived adenovirus infection can be lethal, particularly in the setting of baseline hypogammaglobulinemia in lung transplant recipients. Early diagnosis, aggressive supportive care, and individualized immunosuppression management are essential, but outcomes remain poor, highlighting the need for further research into effective therapies. This abstract is funded by: None