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1.
Chest ; 162(4):A2559, 2022.
Article in English | EMBASE | ID: covidwho-2060962

ABSTRACT

SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Donor-derived cell-free DNA (dd-cfDNA) is a promising plasma analyte for surveillance of rejection and lung transplant (LT) injury. Herein we report our preliminary real-world experiences in concert with standard of practice (SOP) assessments. METHODS: We performed a prospective, cross-sectional, cohort study of a clinically available dd-cfDNA test (the Prospera™ test, Natera, Inc.) combined with SOP clinical assessments − spirometry, fiberoptic bronchoscopy (FOB), donor-specific HLA antibodies (DSA). Single LT dd-cfDNA results were corrected (2X) for lung mass before analysis. Clinical-pathologic cohorts were assigned based on ISHLT guidelines for acute cellular rejection (ACR), uncomplicated chronic lung allograft dysfunction (U-CLAD), and either CoVid-19 or Non-CoVid-19 allograft infection. We also compared median dd-cfDNA fractions between patients experiencing allograft dysfunction (AD) (defined by ΔFEV1≥ -10%) vs stability (STA) and stratified by DSA status. Groups were analyzed by Mann-Whitney (p<0.05) and data expressed as median with 25-75% interquartile range (IQR). RESULTS: A total of 54 plasma samples from 42 unique LT recipients (Single=6, Double=36) were collected at Spectrum Health between November 2021 and February 2022. Primary diagnoses included chronic obstructive pulmonary disease (n=7), interstitial lung disease (n=31), CoVid-19 related ARDS (n=2), CF (n=1) and PAH (n=1). Matching histopathology was available for 68% of dd-cfDNA samples. dd-cfDNA fraction trended 2-fold higher in patient with ACR (1.59%, IQR: 0.09-3.57;n=3) and U-CLAD (1.88%, IQR: 0.88-3.32;n=4) than STA (0.86%, IQR: 0.21-1.62;n=14) patients. Patients with CoVid-19 had significantly higher dd-cfDNA fraction (6.91%, IQR: 2.41-9.77;n=4) than both STA (p=0.035) and NON-CoVid-19 infection cohorts (p=0.049). Although no antibody-mediated rejection (AMR) events were observed, dd-cfDNA fraction was significantly elevated in DSA(+) patients (2.75%, IQR: 1.72-6.25;n=8, class I (4) and II (4)) vs DSA(-) (1.035%, 0.04-1.64;n=46) cohorts (p=0.011). A trend was noted with elevated dd-cfDNA with AD (1.58%, IQR: 0.74-3.62;n=17) vs AS (1.05%, 0.66-1.79;n=37) (p=0.29). CONCLUSIONS: Our preliminary experience is consistent with prior studies, suggesting elevated dd-cfDNA fraction during LT allograft rejection and specific types of infection, in particular, CoVid-19. Of interest, dd-cfDNA detected potential occult molecular injury associated with anti-HLA DSA. CLINICAL IMPLICATIONS: dd-cfDNA fraction assessment after LT represents a valuable clinical tool for clinical surveillance of organ transplant health. DISCLOSURES: Employee relationship with Veracyte, Inc Please note: 2 years by Sangeeta Bhorade, value=Salary Removed 04/03/2022 by Sangeeta Bhorade Employee relationship with Natera Inc Please note: 2/22/22- present Added 04/03/2022 by Sangeeta Bhorade, value=Salary Employee relationship with Natera Please note: 05/2021-present Added 04/04/2022 by Kathryn Crabtree, value=Salary research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria no disclosure on file for Cameron Lawson;No relevant relationships by Edward Murphy Employee relationship with Natera, Inc. Please note: 2020- present by David Ross, value=Salary

2.
Chest ; 162(4):A2552-A2553, 2022.
Article in English | EMBASE | ID: covidwho-2060959

ABSTRACT

SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Fibrotic interstitial lung disease (fILD) can be idiopathic or associated with several underlying conditions and in response to various types of injury. Post COVID-19 fILD is an increasingly recognized clinical entity with the potential for a large burden of morbidity and mortality.[1] We present a series of 6 patients with progressive pulmonary fibrosis as sequela of COVID-19 requiring lung transplantation. CASE PRESENTATION: Four of the 6 patients had known underlying chronic ILD prior to COVID-19 infection (2 with idiopathic pulmonary fibrosis [IPF] and 1 each with scleroderma and rheumatoid arthritis associated ILD). The other 2 patients had no prior history of lung disease and asymptomatic before infection. One of these had a strong family history of IPF. The presentations involved signs of progressive respiratory failure after the initial lung injury from COVID-19. 4 patients were hospitalized during their acute COVID-19 illness and had varying treatments including steroids, antibiotics, anti-virals, convalescent plasma, Tocilizumab, and non-invasive positive pressure ventilation. At the time of transplant evaluation, CT imaging showed prominent interstitial thickening, honeycombing consistent with fibrotic processes for all our patients;PFT revealed severe restrictive ventilatory defect with reduced diffusion capacity ranging 24%-53%;3 patients required venous-venous extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation for 14 and 93 days. The remainder required 6-10 L of supplemental oxygenation at rest. Two patients underwent initial transplant evaluation while in respiratory failure.5 patients received bilateral lung transplantation and one single left lung transplantation.Duration of time between initial COVID-19 induced lung injury and transplantation ranged from 3-13 months, with a median 6-7 months.Lung explant pathology showed advanced usual interstitial pneumonia in all. Superimposed diffuse alveolar damage was noted in 3 cases. Post-transplant to discharge ranged 10-31 days and at 2 months follow-up, all patients were liberated of oxygen needs. All subjects remain alive at a median 11-12 months, with no evidence of allograft dysfunction. DISCUSSION: Since the emergence of SARS-COV2 in 2019, histopathological fibrotic anomalies have been found to be present in up to one-third of those who recover from ARDS due to COVID-19 [2] and their incidence increases as duration of ARDS increases [3]. Further work is required to understand the pathogenesis of the fibrotic process following acute COVID-19. CONCLUSIONS: We highlight this syndrome with our case series of 6 patients who showed progressive fibrotic disease after COVID-19. Patients with pre-exiting ILD appear to be particularly at risk but this entity may occur in those without pre-existing ILD. Lung transplantation offers a viable treatment option for selected patients with an otherwise poor prognosis. Reference #1: 1.Bharat, A., Querrey, M., Markov, N. S., Kim, S., Kurihara, C., Garza-Castillon, R., Manerikar, A., Shilatifard, A., Tomic, R., Politanska, Y., Abdala-Valencia, H., Yeldandi, A. V., Lomasney, J. W., Misharin, A. V., & Budinger, G. (2020). Lung transplantation for pulmonary fibrosis secondary to severe COVID-19. medRxiv : the preprint server for health sciences, 2020.10.26.20218636. https://doi.org/10.1101/2020.10.26.20218636 Reference #2: 2. Rai DK, Sharma P, Kumar R. Post covid 19 pulmonary fibrosis. Is it real threat?. Indian J Tuberc. 2021;68(3):330-333. doi:10.1016/j.ijtb.2020.11.003 Reference #3: 3. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, MacKenna B, Tomlinson L, Douglas IJ, Rentsch CT, Mathur R, Wong AYS, Grieve R, Harrison D, Forbes H, Schultze A, Croker R, Parry J, Hester F, Harper S, Perera R, Evans SJW, Smeeth L, Goldacre B. Factors associated with C VID-19-related death using OpenSAFELY. Nature. 2020 Aug;584(7821):430-436. doi: 10.1038/s41586-020-2521-4. Epub 2020 Jul 8. PMID: 32640463;PMCID: PMC7611074. DISCLOSURES: no disclosure on file for Philip Camp;research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria No relevant relationships by Ryan Hadley No relevant relationships by Sheila Krishnan No relevant relationships by Sheetal Maragiri No relevant relationships by Edward Murphy No relevant relationships by Jay Patel No relevant relationships by Keval Ray No relevant relationships by Gayathri Sathiyamoorthy No relevant relationships by Neel Shah No relevant relationships by Subhan Toor

3.
Chest ; 162(4):A546-A547, 2022.
Article in English | EMBASE | ID: covidwho-2060624

ABSTRACT

SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Immunosuppressed patients are more susceptible to severe infection due to COVID-19. Management of lung transplant recipients is especially difficult due to constant exposure of the graft to the environment, leading to increased risk of rejection and requiring higher levels of maintenance immunosuppressive regimens. Mortality rates for lung transplant recipients with COVID-19 infection have ranged from 15% to 40% in published case series. We report our centers experience in managing lung transplant recipients with COVID-19 infections in a moderate-volume lung transplant center in Grand Rapids, Michigan. METHODS: This is a single center review of all lung transplant recipients with a COVID-19 diagnosis from March 2020 to December 2021. Recipients’ demographics and baseline characteristic, as well as their management, post infectious complications, and mortality data, were reviewed. RESULTS: In 2019, our center performed 48 lung transplants. During the study period, 42 of the 219 (19%) lung transplant recipients followed at our center had COVID-19 infections diagnosed by nasal or nasopharyngeal PCR testing. Twenty-four (57%) were male, mean age of 60.5 (range 25-77). Thirty-six (86%) patients had bilateral lung transplants. The diagnosis leading to their transplantation were COPD (N=18, 43%), idiopathic pulmonary fibrosis (N=12, 29%), cystic fibrosis (N=5, 12%), other pulmonary fibrosis (N=3, 7%), alpha-1 antitrypsin deficiency (N=2, 5%), Sarcoidosis (N=1, 2%), and ARDS (N=1, 2%). Almost all patients were on standard three drug immunosuppressive regimens which included a steroid, calcineurin inhibitor, and nucleotide-blocking agent, at the time of diagnosis. Mean time from transplant to diagnosis of COVID-19 was 34.6 months (range 1 to 104 months). Fifteen (36%) of the patients were unvaccinated. Once diagnosed, patients were advised to monitor their home spirometry and vitals at least daily. They were evaluated weekly via telemedicine by a physician or advanced practice provider. They received the following treatments: monoclonal antibody (N=31, 74%), increased steroids (N=5, 12%), remdesivir (N=2, 5%), Tocilizumab (N=1, 2%). Eleven (26.2%) patients required hospitalization, 4 (10%) required ICU admission and intubation. Mean length of stay was 7.5 days (median of 3 days). Three (7%) patients required oxygen at discharge. Of the 42 infected patients, 3 (7.1%) died on day 3, 16 and 326 days from the date of infection. CONCLUSIONS: Our center reports a lower mortality rate than previously published data in lung transplant recipients infected with COVID-19. We attribute this to availability of the vaccine, early detection and treatment, as well as close monitoring of the patients. CLINICAL IMPLICATIONS: Though COVID-19 infection can have devastating complications in lung transplant recipients, vaccinations and monoclonal antibody treatment reduce morbidity and mortality in this population. DISCLOSURES: No relevant relationships by Phillip Camp research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria no disclosure on file for Ryan Hadley;No relevant relationships by Sheila Krishnan No relevant relationships by Edward Murphy No relevant relationships by Gayathri Sathiyamoorthy

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