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• The study describes management of post-COVID sub-syndromes encountered in our clinic. • Most frequent sub-syndromes: COVID ILD and COVID dyspnea-tachycardia syndrome [DTS]. • COVID ILD received mycophenolate mofetil+prednisone, DTS patients received metoprolol. COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management. To describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic. We retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020–12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment. In treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea. Our descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment. [ABSTRACT FROM AUTHOR]

There are limited data regarding the clinical efficacy of COVID-19 vaccines among lung transplant (LT) patients. We included all LT patients diagnosed with COVID-19 between March 1, 2020, and December 10, 2021 (n = 84; median age 55, range, 20-73 years; males 65.5%). The study group was divided into 3 groups based on the vaccination status (patients who did not complete the primary series for any of the vaccines: n = 58; those with 2 doses of messenger RNA (mRNA) or 1 dose of the adenoviral vector vaccine, vaccinated group: n = 16; those with at least 1 additional dose beyond the primary series, boosted group: n = 10). Pulmonary parenchymal involvement on chest computed tomography scan was less common among the boosted group (P =.009). The proportion of patients with new or worsening respiratory failure was significantly lower among the vaccinated and boosted groups and these patients were significantly more likely to achieve the composite endpoint of oxygen-dependence free survival (P =.02). On multivariate logistic regression analysis, higher body mass index, restrictive lung disease as the transplant indication, and preinfection chronic lung allograft dysfunction were independently associated with acute or acute on chronic respiratory failure while being on therapeutic dose anticoagulation and having received the booster dose had a protective effect. COVID-19 vaccines appear to have several favorable effects among LT patients with breakthrough infections including lower likelihood of allograft involvement on imaging (among boosted patients), need of hospitalization, and complications such as new or worsening respiratory failure. [ABSTRACT FROM AUTHOR]

The proportion of lung transplant candidates with comorbid renal dysfunction (RD) may rise as sicker patients are being considered for lung transplant (LT). There is lack of data regarding the characteristics and outcome of patients with RD and the role of simultaneous lung-kidney transplant (SLuKi) among these patients. The United Network of Organ Sharing database was queried for adult patients (18 years or older) undergoing LT between 1995 and 2014. Pretransplant RD was defined as estimated glomerular filtration rate (eGFR), using the Chronic Kidney Disease Epidemiology Collaboration equation of <60 mL/min/1.73 m2 at the time of transplant listing. The recipient, donor, and procedure-related variables and survival were compared among patients with RD undergoing LT alone (split on the basis of eGFR impairment: 30-60 mL/min/1.73 m2 and ≤ 30 mL/min/1.73 m2) vs those with SLuKi. The frequency of pretransplant RD was 5.42% (n = 1337). Patients with RD have significantly higher 1-year mortality (23.2% vs 15%; P <.001) and 3-year mortality (38.3% vs 28%; P <.001) than patients with eGFR > 60mL/min/1.73 m2. The proportion of patients with RD undergoing SLuKi was 2.84% (38 of 1337). Both the number and proportion of patients undergoing SLuKi progressively increased during the study period, especially in the lung allocation score era (30 of 38 SLuKi patients in the post lung allocation score era (linear R 2 = 0.641, P <.001). The patients who underwent SLuKi were significantly younger, had lower body mass index, serum albumin, and listing eGFR (P <.001 for all comparisons). Patients with SLuKi were more likely to have cystic fibrosis or vascular diseases as the underlying diagnosis (29.7% vs 13.8%, P =.004). Despite higher need of early dialysis support after transplant, there was no difference in the 30-day, 1-year, or 3-year survival between the 2 groups. A significant proportion of LT candidates have a pre-existing RD, and this comorbidity is associated with significantly worse 1- and 3-year survival. Despite being the sicker group at baseline, patients with RD who undergo SLuKi have 1-year outcomes similar to patients with LT alone. • A significant proportion of patients listed for lung transplant have preexisting renal dysfunction (estimated glomerular filtration rate < 60 mL/min/1.73m2), which is associated with worse 1- and 3-year survival • The proportion of patients undergoing simultaneous lung-kidney transplant has been on the increase especially in the post lung allocation score era • Patients with pretransplant history of dialysis support and an underlying diagnosis of cystic fibrosis or vascular diseases were likely to undergo simultaneous lung-kidney transplant • Despite a longer hospital stay after the transplant, 30-day or 1-year survival among patients with simultaneous lung-kidney transplant was similar to other patients with renal dysfunction [ABSTRACT FROM AUTHOR]

A lung transplant (LT) patient developed 2 distinct episodes of COVID-19, confirmed by whole-genome sequencing, which was caused by the Delta, and then followed 6 weeks later, by the Omicron variant. The clinical course with Omicron was more severe, leading us to speculate that Omicron may not be any milder among LT patients. We discuss the potential mechanisms behind the Omicron not being any milder among LT patients and emphasize the need for outcomes data among these patients. Until such data become available, it may be prudent to maintain clinical equipoise as regards the relative virulence of the newer variants among LT patients. [ABSTRACT FROM AUTHOR]

There are limited data on management strategies and outcomes among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). We implemented management protocols based on the best available evidence and consensus among multidisciplinary teams. The current study reports our experience and outcomes using this protocol-based management strategy. We included single or bilateral LT patients who tested positive for SARS-CoV-2 on nasopharyngeal swab between March 1, 2020, to December 15, 2020 (n = 25; median age: 60, range 20-73 years; M: F 17:8). A group of patients with Respiratory Syncytial Virus (RSV) infection during 2016-18 were included to serve as a comparator group (n = 36). As compared to RSV, patients with COVID-19 were more likely to present with constitutional symptoms, spirometric decline, pulmonary opacities, new or worsening respiratory failure, and need for ventilator support. Patients with SARS-CoV-2 infection were less likely to receive a multimodality treatment strategy, and they experienced worse post-infection lung function loss, functional decline, and three-month survival. A significant proportion of patients with COVID-19 needed readmission for worsening allograft function (36.4%), and chronic kidney disease at initial presentation was associated with this complication. Lower pre-morbid FEV 1 appeared to increase the risk of new or worsening respiratory failure, which was associated with worse outcomes. Overall hospital survival was 88% (n = 22). Follow-up data was available for all discharged patients (median: 43.5 days, range 15-287 days). A majority had persistent radiological opacities (19/22, 86.4%), with nearly half of the patients with available post-COVID-19 spirometry showing > 10% loss in lung function (6/13, median loss: 14.5%, range 10%-31%). Despite similar demographic characteristics and predispositions, LT patients with COVID-19 are sicker and experience worse outcomes as compared to RSV. Despite the availability of newer therapeutic agents, COVID-19 continues to be associated with significant morbidity and mortality. [ABSTRACT FROM AUTHOR]

Air trapping (AT) is one of the hallmarks of allograft dysfunction after lung transplantation (LT). Inert gas‒based ventilation‒perfusion (VQ) lung scintigraphy has excellent sensitivity in the detection of AT. We reviewed the charts of patients who underwent single or double LT between January 2012 and December 2014 (N = 193). Patients without a VQ scintigraphy at the first annual visit (n = 16) and those who did not survive till 1 year (n = 26) were excluded (final n = 151, mean age = 55.8 [SD =14] years, male = 85, female = 66). VQ scintigraphy was independently reviewed and reconciled for the presence and severity of AT by 2 investigators blinded to the clinical data (D.F.P. and D.M.). A 3-year post-transplant survival was the primary end-point. AT was common (n = 73, 48.3%). Patients with obstructive lung diseases as the underlying diagnosis (adjusted odds ratio [OR], 4.36, 95% CI: 1.64‒11.6; p = 0.003) and those with lower body mass index (BMI) (BMI < 25 kg/m2 and 25‒30 kg/m2; p < 0.001) had an increased risk of developing AT in the allograft. The presence of AT (adjusted OR, 2.33, 95% CI: 1.01‒5.36; p = 0.04) and peak forced expiratory volume in 1 sec (FEV 1) <60% predicted during the first year after LT were independently associated with 3-year mortality. The association of AT with post-transplant mortality was the strongest among patients with BMI <30 kg/m2 and peak FEV 1 <60% predicted. The finding of AT on VQ scintigraphy at the first annual visit after LT is independently associated with worse post-transplant mortality. The sub-group of patients who fail to achieve a peak FEV 1 of 60% predicted during the first year after LT appears to be the key driver of this association. [ABSTRACT FROM AUTHOR]

Chronic Lung Allograft Dysfunction (CLAD) remains the major limitation in long term survival after lung transplantation. Our objective is to evaluate for the presence of autoantibodies to self-antigens, which is a pathway along with complex interplay with immune as well as non-immune mechanisms that leads to a fibroproliferative process resulting in CLAD. Serum profiles of IgG autoantibodies were evaluated using customized proteomic microarray with 124 antigens. Output from microarray analyzed as antibody scores is correlated with bronchiolitis obliterans (BOS) subtype of CLAD using Mann-Whitney U test or Fisher exact test. Autoantibodies were evaluated for their predictive value for progressive BOS using a Cox proportional hazard model. BOS free survival and overall survival was analyzed using Kaplan-Meier survival analysis. Forty- two patients included in the study are grouped into "stable BOS" and "progressive BOS" for comparisons. Pulmonary fibrosis is the major indication for lung transplantation in our cohort. Progressive BOS group had significantly worse survival (p < 0.005). Sixteen IgG autoantibodies are significantly elevated at baseline in progressive BOS group. Six among them correlated with worse BOS free survival (p < 0.05). In addition, these six IgG autoantibodies remain elevated at three months and one year after lung transplantation. Pre-existing IgG autoantibodies correlate with progressive BOS and survival in a single center, small cohort of lung transplant recipients. Further validation with larger sample size, external cohort and confirmation with additional tissue, bronchoalveolar lavage samples are necessary to confirm the preliminary findings in our study. [ABSTRACT FROM AUTHOR]

Background There has been little investigation into the potential interaction of recipient characteristics with the association of pre-transplant renal functions and survival after lung transplantation. In this study we tested the hypothesis that association of pre-transplant renal function and post-transplant mortality varies among recipient subgroups. Methods We queried the United Network for Organ Sharing (UNOS) database for adult patients (≥18 years of age) undergoing lung transplantation between May 2005 and March 2015. The study population ( n = 15,540) was split into 3 groups (90 to 150, 60 to 89.9 and 30 to 59.9 ml/min/1.73 m 2 ) based on the estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) at the time of listing. We utilized multivariable inverse probability weighted Cox proportional hazard models to compare the association of glomerular filtration rate (GFR) groups with mortality among recipient subgroups. Results Overall, there was an independent and graded inverse association between the estimated GFR (eGFR) and mortality, with the hazard of mortality significantly rising with listing eGFR <60 ml/min/1.73 m 2 . The association between low eGFR and mortality was more consistent and stronger for older (>45 years), non–African-American and non-diabetic patients as well as those with low lung allocation score (LAS <40). Among the diagnosis groups, patients with vascular diseases had the strongest association between low eGFR and poor survival. Sensitivity analyses conducted using an alternate equation to estimate the GFR (Modification of Diet in Renal Disease) supported these associations. Conclusions Prognostic significance of pre-transplant renal functions varies significantly among recipient subgroups. It may be appropriate to develop a customized approach toward assessing and interpreting renal function to determine transplant candidacy. [ABSTRACT FROM AUTHOR]

Background Duration of index hospitalization after lung transplantation (LTx) is an important variable that has not received much attention. We sought to determine independent predictors of prolonged hospital length of stay (LOS) and its association with early and late outcomes. Methods The United Network of Organ Sharing database was queried for adult patients undergoing LTx between 2006 and 2014 ( N = 14,320). Patients with dual organ or previous transplantation and patients who died during the first 25 days after LTx were excluded ( n = 12,647, mean age 55.2 years ± 13.1). Primary outcome was prolonged LOS (>25 days) (3,251/12,647; 25.7%). Donor, recipient, and procedure-related variables were analyzed as potential predictors of prolonged LOS. Association of prolonged LOS with 1-year and 5-year survival was evaluated using Cox proportional hazards analysis. Results Independent predictors of prolonged LOS included serum albumin, lung allocation score, functional status, and need of extracorporeal membrane oxygenation or ventilator support at the time of transplant; donor age >40 years; gender mismatch (female donor to male recipient); donor body mass index; African American ethnicity; ischemic time >6 hours; and double LTx. Prolonged LOS was independently associated with increased mortality at 1 year (hazard ratio, 3.96; 95% confidence interval, 3.48–4.50; p < 0.001) and 5 years (hazard ratio, 2.00; 95% confidence interval, 1.79–2.25; p < 0.001). Conclusions A significant proportion of patients have a prolonged LOS after LTx, and several recipient, donor, and procedure-related variables are independent predictors of this outcome. Patients with prolonged LOS after LTx have significantly increased risk of death at 1 year and 5 years. [ABSTRACT FROM AUTHOR]

Background Atrial fibrillation (AF) is a common complication after lung transplantation (LT). Since the lung allocation score (LAS) was implemented in 2005, there has been significant evolution in the practice of LT, necessitating re-evaluation of this arrhythmia. Methods One hundred thirty-one patients undergoing LT between January 2011 and April 2013 were reviewed retrospectively to assess the occurrence of AF and its outcomes (mortality, morbidity measures, treatment strategies). Uni- and multivariate logistic regression models were constructed to ascertain predictors of AF. Results Forty-six patients (35.1%) developed post-operative AF at 4.65 ± 3.68 days post-LT. The AF group was older (60.07 vs 54.48 years, p = 0.01), and had higher rates of cardiopulmonary bypass (CPB) (73.33% vs 43.53%, p = 0.001). There was no difference in mortality, ICU length of stay (LOS) and ventilator days; however, the AF group had a significantly higher mean hospital LOS by 8.43 days (17.09 vs 25.52, p = 0.04). Age (OR = 1.04, p = 0.03) and CPB (OR = 3.68, p = 0.002) were identified as predictors of AF by stepwise logistic regression after adjusting for gender, history of AF, type of LT, pulmonary hypertension and LT indication. In the AF group, 78.26% of patients required combination therapy. Anti-arrhythmics were used in 52.17% of patients. Dofetilide/ibutilide use was not associated with increased mortality. A total of 97.82% were in sinus rhythm at discharge. Conclusions To our knowledge, this is the first study to examine post-operative AF exclusively in the post-LAS era. Incidence of AF after LT is 35%. It increases hospital LOS, but not mortality. Management of AF is challenging and dofetilide/ibutilide serve as effective adjuncts to current therapy. [ABSTRACT FROM AUTHOR]

Primary graft Dysfunction (PGD) results in significant mortality and morbidity after lung transplantation (LT). The objective of this study was to evaluate if pre-existing antibodies to self-antigens in sera of LT recipients are associated with PGD. The serum profiles of IgG and IgA autoantibodies were analyzed using a customized proteomic microarray bearing 124 autoantigens. Autoantibodies were analyzed using Mann-Whitney U test or Fisher exact test. The association of the autoantibodies with clinical phenotypes and survival was analyzed by Kaplan-Meier Survival Analysis. Receiver operating curve characteristics (ROC) were calculated to evaluate the predictive value of the autoantibodies for PGD. 51 patients were included in this study. Autoantigen microarray analysis on the pre-transplantation samples identified 17 IgA and 3 IgG autoantibodies which were significantly higher in recipients who developed PGD compared to those who did not (adjusted p <.05 and fold change>1.5). 6 IgA Abs were significantly associated with survival. Taken as a panel, an elevation of 6 IgA Abs had significant predictive value for PGD. Area under the curve value for the panel was 0.9413 for PGD with ROC analysis. Notably, 6 of the 17 IgA autoantigen targets are belong to proteoglycan family of extracellular matrix proteins. Pre-existing IgG and IgA autoantibodies in LT patients correlate with PGD and with survival in a single center, small cohort of lung transplant recipients. Further validation is needed to confirm the findings in the study. • Primary Graft dysfunction (PGD) results in significant mortality and morbidity after lung transplantation. • Presence of pre-existing antibodies (IgG, IgA) to self-antigens correlate with PGD • Panel of 6 IgA autoantibodies at baseline seem to have significant predictive value for PGD and survival. [ABSTRACT FROM AUTHOR]