Vissichelli, Nicole C.

Abstract Rationale Fungal infections remain a major cause of morbidity and mortality post lung transplant due to unique exposure of the allograft to the external environment and the intensity of immunosuppression. Single-center studies have described variable rates of fungal infections. Contemporary population-level data with temporal trends, pathogen distribution, and associated outcomes are limited. Leveraging a large multicenter real-world dataset, we aimed to characterize incidence, prevalence and clinical outcomes of fungal infections among adult lung-transplant recipients. Methods Data were obtained from the TriNetX Global Collaborative Network (160 HCOs). Adult lung-transplant recipients (≥18 years) were identified between 2005 and 2024, using ICD and CPT procedure codes. Patients with solid organ transplants other than lung, combined-organ transplant or stem-cell transplant and HIV patients were excluded. Patients with pre transplant fungal infections were also excluded. Pre-transplant characteristics included demographics, comorbidities within a year, laboratory values within seven days, and medication within 90 days before transplantation. Post-transplant fungal infections were identified using ICD-10 codes for Aspergillus, Candida, Cryptococcus, Mucorales, Histoplasma, Blastomyces, Coccidioides, and Pneumocystis. TriNetX platform was utilized for statistical analysis. Incidence and prevalence of infections, all-cause mortality and transplant rejection were analyzed. Results A total of 12,857 adult lung-transplant recipients were identified. The mean age at transplantation was 57.6 ± 13.4 years, with a male predominance of (57%) and majority were white (65%). Average BMI was 26.8 ± 5.7 kg/m². The most common pulmonary conditions were COPD (15%), pulmonary fibrosis (17%), pulmonary hypertension (9%), bronchiectasis (3%), and cystic fibrosis (3%). Pre-transplant fungal and viral screening assays were rarely available (<1%). Medication exposure within 90 days prior to transplant demonstrated prednisone prescription (17%) methylprednisolone (7%), tacrolimus (6%), and mycophenolate mofetil (7%). Azathioprine and basiliximab were used in 2% each. Systemic antifungals (voriconazole, posaconazole, or fluconazole) in approximately 1% each.The overall incidence of post-transplant fungal infection was 3 % across full study period, rising to 7% in the modern era (2015-2024). Most frequently identified pathogens were Candida spp. (4.8%) and Aspergillus spp. (2.9%), followed by Pneumocystis Jirovecii (0.5%). Infection rates increased from 22 per 1,000 (2005-2014) to 75 per 1,000 (2015-2024) suggestive of improved diagnostic sensitivity and data capture, and longer post-transplant survival. All-cause mortality 5-year post transplant was 22.1%, and rejection rate was 22.5%. Conclusion Our study highlights a rising burden of fungal infections among lung-transplant recipients with potential implications for early post-transplant surveillance and antifungal prophylaxis strategies. This abstract is funded by: None

Abstract Rationale Fungal infections are common after lung transplantation and may adversely affect graft function and survival, but long-term outcomes remain incompletely defined. Using a large multicenter real-world dataset, we aimed to study the impact of post-transplant fungal infections on clinical outcomes of lung transplant recipients. Methods We conducted a retrospective, cohort study using the TriNetX Global Collaborative Network, which aggregates de-identified electronic health records from >160 healthcare organizations across North America, Europe, and Asia. Adult lung transplant recipients (≥18 years) between 2005 and 2024 were identified using ICD-10 and CPT codes. Patients with post-transplant fungal infection (aspergillosis, candidiasis, mucormycosis, histoplasmosis, coccidioidomycosis, blastomycosis) and matched controls without fungal infection within one year before or any time after transplant were identified. The index date was the date of transplantation. Propensity-score matching was performed on demographics, comorbidities, laboratory values, procedures and immunosuppressive medications. Outcomes included all-cause mortality (primary), allograft rejection, and chronic lung allograft dysfunction (CLAD) at 6 months, 1 year, 3 years, and 5 years. Kaplan-Meier and Cox proportional hazards models were used to estimate risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs). Analyses were conducted in TriNetX Analytics (v25.0, Cambridge, MA). Results A total of 3,083 patients with post-transplant fungal infection and 11,625 patients without infection were identified. Mean age was 58 ± 13 years, and 56% were male. The most common pulmonary comorbidities were chronic obstructive pulmonary disease, unspecified pulmonary fibrosis, idiopathic pulmonary fibrosis and bronchiectasis. Immunosuppression exposure was similar across groups. After propensity score matching across 56 clinical variables, both groups (1,790 per group) were well balanced. Mortality was higher in the fungal infection cohort at all follow-up points: 13.% vs 9% at 6 months (RR 1.45, 95% CI 1.2-1.75, p = 0.001), 17.8% vs 13% at 1 year (RR 1.36, p = 0.0001), 27.7% vs 21% at 3 years (RR 1.28, p < 0.0001), and 33 % vs 25% at 5 years (RR 1.32, p < 0.0001). Allograft rejection remained consistently higher (46-61% vs 22-34%), while CLAD occurred two- to three-fold more frequently (1.8-5.7% vs 0.7-2%). Conclusion Post-transplant fungal infection is independently associated with significantly increased mortality, acute rejection, and CLAD following lung transplantation. These findings underscore the need for early fungal surveillance, optimized antifungal prophylaxis, and individualized immunosuppression strategies to improve long-term patient outcomes. This abstract is funded by: None

ImportanceThere is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).ObjectiveTo determine whether the use of steroids within 2 days of admission for non–MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.Design, Setting, and ParticipantsThis cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non–MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.ExposureAdministration of steroids within 2 days of admission.Main Outcomes and MeasuresLength of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.ResultsA total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score–matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.Conclusions and RelevanceSteroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.