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Background Antibody-mediated rejection (AMR) after lung transplantation remains enigmatic, and there is no consensus on the characteristic clinical, immunological, and histological features. Methods We performed a retrospective, single-center cohort study and identified cases of acute AMR based on the presence of circulating donor-specific human leukocyte antigen (HLA) antibodies (DSA), histologic evidence of acute lung injury, C4d deposition, and clinical allograft dysfunction. Results We identified 21 recipients with acute AMR based on the above criteria. AMR occurred a median 258 days after transplantation; 7 recipients developed AMR within 45 days of transplantation. All patients had clinical allograft dysfunction, DSA, histology of acute lung injury, and capillary endothelial C4d deposition. Fifteen recipients improved clinically and survived to hospital discharge, but 6 died of refractory AMR. One survivor had BOS at the time of diagnosis of AMR; 13 of the 14 remaining survivors developed chronic lung allograft dysfunction (CLAD) during follow-up. Overall, 15 recipients died during the study period, and the median survival after the diagnosis of AMR was 593 days. Conclusions Acute AMR can be a fulminant form of lung rejection, and survivors are at increased risk of developing CLAD. The constellation of acute lung injury, DSA, and capillary endothelial C4d deposition is compelling for acute AMR in recipients with allograft dysfunction. This clinicopathological definition requires validation in a multicenter cohort but may serve as a foundation for future studies to further characterize AMR.

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As the short telomere defect has been linked to the pathogenesis of IPF in some cases, our data indicate that impaired CMV immunity may be a systemic manifestation of telomere-mediated disease in these patients. Identifying this high-risk subset of lung transplant recipients has implications for risk assessment, management and potential strategies for averting posttransplant CMV morbidities.

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Background Previous studies have suggested that azithromycin improves lung function in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). However, these studies did not include a non-treated BOS control cohort or perform survival analysis. This study was undertaken to estimate the effect of azithromycin treatment on survival in lung transplant recipients with BOS. Methods We conducted a retrospective cohort study of consecutive lung transplant recipients who developed BOS between 1999 and 2007. An association between azithromycin treatment and death was assessed using univariate and multivariable time-dependent Cox regression analysis. Results Of the 178 recipients that developed BOS in our study, 78 developed BOS after 2003 and were treated with azithromycin. The azithromycin treated and untreated cohorts had similar baseline characteristics. Univariate analysis demonstrated that azithromycin treatment was associated with a survival advantage and this beneficial treatment effect was more pronounced when treatment was initiated during BOS stage 1. Multivariable analysis demonstrated azithromycin treatment during BOS stage 1 (adjusted hazard ratio=0.23, p=0.01) and absolute FEV1 value at the time of BOS stage 1 (adjusted hazard ratio=0.52, p=0.003) were both associated with a decreased risk for death. Conclusion In lung transplant recipients with BOS stage 1, azithromycin treatment initiated before BOS stage 2 was independently associated with a significant reduction in the risk of death. This finding supports the need for a randomized controlled trial to confirm the impact of azithromycin on survival in lung transplant recipients.

Background We studied humoral responses after COVID-19 vaccination across varying causes of immunodeficiency. Methods Prospective study of fully-vaccinated immunocompromised adults (solid organ transplant (SOT), hematologic malignancy, solid cancers, autoimmune conditions, HIV infection) versus non-immunocompromised healthcare-workers (HCW). The primary outcome was the proportion with a reactive test (seropositive) for IgG to SARS-CoV-2 receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. Results 1271 participants enrolled: 1,099 immunocompromised and 172 HCW. Compared to HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (p<0.01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus mRNA-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines, after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r=0.89, p<0.0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. Conclusion Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCW. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.