Background Reports on outcomes following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in lung transplant recipients remain limited. Methods We performed a single‐center, observational study of outcomes in lung transplant recipients diagnosed with SARS‐CoV‐2 between 5/1/2020 and 3/15/2022 that were followed for a median of 123 days. We analyzed changes in spirometry, acute lung allograft dysfunction (ALAD) incidence, hospitalization, mechanical ventilation needs, secondary infection, and survival. Results In our cohort of 336 patients, 103 developed coronavirus disease (COVID) (27 pre‐Delta, 20 Delta, and 56 Omicron‐era). Twenty‐five patients (24%) required hospitalization and 10 patients ultimately died (10%). Among 85 survivors who completed ambulatory spirometry, COVID‐19 did not alter change in forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) over time compared to the preceding 6 months. The pre‐COVID FEV1 change was −0.05 ml/day (IQR −0.50 to 0.60) compared to −0.20 ml/day (IQR −1.40 to 0.70) post‐COVID (p = .16). The pre‐COVID change in FVC was 0.20 ml/day (IQR −0.60 to 0.70) compared to 0.05 ml/day (IQR −1.00 to 1.10) post‐COVID (p = .76). Although the cohort overall had stable lung function, 33 patients (39%) developed ALAD or accelerated chronic lung allograft dysfunction (FEV1 decline >10% from pre‐COVID baseline). Nine patients (35%) with ALAD recovered lung function. Within 3 months of acute COVID infection, 18 patients (17%) developed secondary infections, the majority being bacterial pneumonia. Finally, vaccination with at least two doses of mRNA vaccine was not associated with improved outcomes. Conclusions This study describes the natural history of SARS‐CoV‐2 infection in a large cohort of lung transplant recipients. Although one third of patients develop ALAD requiring augmented immunosuppression, infection with SARS‐CoV‐2 is not associated with worsening lung function.

The authors had full oversight over study design, data collection and analysis, and article preparation. Lung TransplantationBackground. Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker for the diagnosis of acute allograft injury within the first 1 to 2 y after lung transplant, but its utility for diagnosing chronic lung allograft dysfunction (CLAD) has not yet been studied. Understanding baseline dd-cfDNA kinetics beyond the initial 2 y posttransplant is a necessary first step in determining the utility of dd-cfDNA as a CLAD biomarker. We seek to establish baseline dd-cfDNA% levels in clinically stable lung allograft recipients who are >2 y posttransplant. Methods. We performed a prospective, single-center, observational study to identify plasma dd-cfDNA levels in clinically stable lung allograft recipients >2 y posttransplant. Results. Fiftyone subjects were enrolled and ≥3 baseline dd-cfDNA measurements were acquired during a median of 252 d. The median baseline percent dd-cfDNA level in our cohort was 0.45% (interquartile range [IQR], 0.26-0.69). There were statistically significant differences in dd-cfDNA based on posttransplant duration (≤5 y posttransplant median 0.41% [IQR, 0.21-0.64] versus >5 y posttransplant median 0.50% [IQR, 0.33-0.76]; P < 0.02). However, the clinical significance of this small change in dd-cfDNA is uncertain because this magnitude of change is within the biologic test variation of 73%. Conclusions. This study is the first to define levels of dd-cfDNA in clinically stable patients who are >2 y post-lung transplant. These findings lay the groundwork for the study of dd-cfDNA as a possible biomarker for CLAD.

Background. Donor-derived cell-free DNA (dd-cfDNA%) is a biomarker of early acute lung allograft dysfunction (ALAD), with a value of ≥1.0% indicating injury. Whether dd-cfDNA% is a useful biomarker in patients >2 y posttransplant is unknown. Our group previously demonstrated that median dd-cfDNA% in lung recipients ≥2 y posttransplant without ALAD was 0.45%. In that cohort, biologic variability of dd-cfDNA% was estimated by a reference change value (RCV) of 73%, suggesting that change exceeding 73% may be pathologic. In this study, we aimed to determine whether dd-cfDNA% variability or absolute thresholds are optimal for detecting ALAD. Methods. We prospectively measured plasma dd-cfDNA% every 3 to 4 mo in patients ≥2 y post–lung transplant. ALAD was defined as infection, acute cellular rejection, possible antibody-mediated rejection, or change in forced expiratory volume in 1 s >10%, and was adjudicated retrospectively. We analyzed area under the curve for RCV and absolute dd-cfDNA% and reported performance of RCV ≥73% versus absolute value >1% for discriminating ALAD. Results. Seventy-one patients had ≥2 baseline measurements of dd-cfDNA%; 30 developed ALAD. RCV of dd-cfDNA% at ALAD had a greater area under the receiver operator characteristic curve than absolute dd-cfDNA% values (0.87 versus 0.69, P = 0.018). Test characteristics of RCV >73% for ALAD diagnosis were sensitivity 87%, specificity 78%, positive predictive value 74%, and negative predictive value 89%. In contrast, dd-cfDNA% ≥1% had sensitivity 50%, specificity 78%, positive predictive value 63%, and negative predictive value 68%. Conclusions. Relative change in dd-cfDNA% has improved test characteristics for diagnosing ALAD compared with absolute values.

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