key: cord-0872874-1evbaka1
authors: Sam, T.; Askar, M.; Naik, C.; Vandervest, K.; Rosenblatt, R.; Grazia, T.; Mathai, S.
title: Alloimmune Response After SARS-CoV-2 Vaccination in Lung Transplant
date: 2022-04-30
journal: The Journal of Heart and Lung Transplantation
DOI: 10.1016/j.healun.2022.01.1259
sha: aa737a3719eb42c593dd6dcff692d9416136d142
doc_id: 872874
cord_uid: 1evbaka1

Purpose The effect of SARS-CoV-2 vaccination on de novo donor specific antibodies (dnDSA) in lung transplant recipients (LTRs) is unknown. We reviewed dnDSA results following SARS-CoV-2 vaccination in LTRs based on SARS-CoV-2 IgG response. Methods LTRs were tested for SARS-COV-2 Multi-target IgG at 3 and 6 months post-vaccination. LTRs who received at least 1 dose of SARS-CoV-2 vaccine between 12/01/2020 to 07/01/2021 were included in this retrospective review. We compared patients based on anti-spike (S-IgG) results. Results We reviewed 55 LTR charts with S-IgG results. Only 24 (44%) developed S-IgG by 6 months after vaccination. Differences between S-IgG positive and negative groups are shown in the table. Those with positive S-IgG were further from transplant, had lower mycophenolate doses, more likely to have had COVID infection pre-vaccination, and had lower rates of hypogammaglobulinemia. Only 3 patients (5.5%) developed dnDSA after vaccination; all were S-IgG positive. One had history of antibody mediated rejection (AMR), while another was initially negative for dnDSA at 6 weeks post-vaccination, but turned positive at 7 months (low level Class II DSA). One patient who had prior DSA developed clinical rejection (AMR) with Class II dnDSA (DR7) and significant rise in prior DSA (DR53, DQ2) to >20,000 MFI at 6 months (negative at 3 months) post-vaccine in the setting of new viral infection. Another patient was excluded from this study as he died of AMR and dnClass II DSA (DQ8 > 10,000 MFI, DQ6, DR4 within 5 days of dose) 2 months after his first Pfizer/BioNTech dose, but before 3 month S-IgG testing. Conclusion In our cohort, dnDSA after SARS-CoV-2 vaccination was uncommon but observed in patients who developed S-IgG response. The single AMR case occurred late and may be related to infection. In the excluded patient with acute AMR early after vaccine, correlation to S-IgG is unknown as the patient did not survive to 3 months. Further studies are needed to determine the impact of additional vaccine doses and long-term outcomes and immune responses.

shock, mechanical circulatory support (MCS) in that setting has evolved and different devices are available. Case Report: A 59-year-old male patient was admitted in 06/2020 for inferior pericardiectomy due to hemodynamic instability after right ventricular (RV) lead dislocation with pericardial effusion. He presented severely impaired biventricular function with indication for Impella Ò 5.5 implantation. With further RV deterioration, a temporary RVAD with a Protek-Duo Ò canula + CentriMag TM pump was implanted. The patient was weaned from nitric oxide (NO) inhalation and extubated on the first postoperative day (POD). However, he developed hyperbilirubinemia with Bilirubin > 13 mg/dl under full t-RVAD support and continuous inotrope therapy, with acute-on-chronic renal failure leading to anuria. High urgent listing for transplantation (HTX) was not an option in this clinical situation. The patient gave consent to biventricular assist device (BIVAD) implantation. On POD 19 after pericardiectomy, a HeartMate 3 TM LVAD in a hybrid combination with a Berlin Heart Ò Excor RVAD was successfully implanted. He was weaned from NO and extubated within 24 hours. On POD 3 after BIVAD, a right ventricular chamber upgrade to a 80ml chamber was performed. After 4 weeks on BIVAD support, the patient developed a haemothorax with need for surgical revision due to overanticoagulation. Thereafter, he slowly recovered and could be discharged from ICU to the normal care ward after 92 days. He has been free from dialysis since 11/2020 and was discharged home with a Berlin Heart-Ò Excor mobile in 12/2020. Active listing for HTX was granted in 06/ 2021, one year after first admission. The patient is now stable in NYHA 3 with BIVAD support at home. Summary: Treatment options in biventricular failure are limited. In countries with long waiting list time, hybrid BIVAD support with a continuous flow LVAD and a pulsatile paracorporeal RVAD is feasible and allows successful discharge. Further research is needed to evaluate this clinical approach. Introduction: The optimal surgical technique for HVAD to HeartMate 3 left ventricular assist device (LVAD) exchange will be patient dependent. We report a successful minimally invasive approach. Case Report: Case: A 33-year-old woman with Adriamycin induced cardiomyopathy status post destination therapy HVAD in 2006 developed progressive alarms. Imaging revealed a large left ventricular (LV) thrombus attached to the inflow cannula. An elective HVAD to HeartMate 3 exchange was considered. Pre-operative planning: CT imaging was used to generate a three dimensional (3D) model of the heart and HVAD (A). To aid in planning both new device placement and the anastomosis between the HVAD and HeartMate 3 outflow grafts, a 3D model was generated (B). Surgical description: A left thoracotomy and 5th rib resection was used to access the HVAD and LV apex (C). The femoral vessels were cannulated for cardiopulmonary bypass and the heart was minimally manipulated. The HVAD pump, apical cuff, and exposed driveline were removed and LV clot evacuated. The HeartMate 3 apical cuff was secured to the LV apex and the pump placed in standard position (D). The HeartMate 3 (14mm) outflow graft was anastomosed to the retained HVAD (10mm) outflow graft by beveling the HVAD outflow graft (E, F). The HeartMate 3 driveline was then tunneled out of the left upper abdominal quadrant using a double tunnel technique. The thoracotomy was then closed in a standard fashion. Summary: Outcome: The total bypass time was 1 hour and 20 minutes. She arrived to the intensive care unit on low dose epinephrine and vasopressin, which were rapidly weaned off. She required a total of 2 packed red blood cell transfusions. She was extubated on post-operative day 3 with normal hemodynamics and intact end organ function. She was eventually discharged in stable condition. 3D modeling was invaluable in preprocedural planning and final outcomes.

Lipoic Acid F127@lpp Nanoparticles as a New Therapeutic Tool for Delivering Active Molecules C. Castellani, 1 C. Radu, 1 L. Morillas Becerril, 1 I. Barison, 1 M. Fedrigo, 1 A. Giarraputo, 1 M. Virzì, 2 P. Simioni, 1 C. Basso, 1 E. Papini, 1 R. Tavano, 1 M. Fabrizio, 1 G. Vescovo, 3 and A. Angelini. 1 1 University of Padua, Padova, Italy; 2 Hospital of Vicenza, Hospital of Vicenza, Italy; and the 3 Hospital of Padua, Padova, Italy.

Purpose: Polylipoic acid-based nanoparticles (F127@PLA-NPs) have a great potential as nanovectors, and may represent a future potential therapeutic tool for delivering active molecules to different organs in complex diseases. However, their tissue distribution, accumulation, persistence and clearance in vivo are not known yet, as well as specific cellular penetration and ability to deliver subgenomic particles to the intracellular space. We have investigated it in vitro and in vivo in heart, kidney and in splancnic organs of healthy rodents. Methods: Healthy Sprague-Dawley rats were injected with 10mg/Kg of F127@PLA-NPs rhodamine conjugated via tail vein and compared with 7 controls. Rats were sacrificed at different time points from 10 minutes to 2 months after NPs injection. NPs fluorescence and MFI rate in whole collected organs and in the different cell types have been measured using an "image analysis quantification algorithm" software of confocal microscope Results: NPs fluorescence was identified immediately after injection in the heart and later on into splanchnic organs. After 3 hours, the heart was able to retain an amount of NPs 2-fold higher than that observed in the liver (30.63 §10.78MFI vs 13.93 §1.42MFI) and about 5-times higher than lungs and spleen and three time higher than kidney. The heart showed the maximal NPs accumulation (3.69MFI/h) compared to all the other organs such as kidney (0.465MFI/h at 3h), liver (0.2MFI at 3days) and spleen (1.06MFI at 1h). Myocytes showed 25.06 §5.13MFI/cell at 3 hours with a clearance rate of -0.4MFI/h/cell while kidney tubular cells showed their maximal accumulation rate at 3days with 19.14 §3.148MFI/cell. Liver, instead, revealed a different kinetic between hepatocytes and kupffer cells (18.94 §3.03 vs 37.64 §19.14MFI at 1day respectively). No organ damage and histopathological lesions were observed after NPs injection. In vitro studies showed the ability of NPs to vehiculate miRNAs to intracellular cardiomyocytes. Conclusion: his new approach constitutes a biological minimally invasive and safe method to deliver active molecules to target organs and cells such as heart and kidney Purpose: Quilty Lesions (QL) are enigmatic polytypic inflammatory cellular aggregates seen in some heart transplant biopsies. The study was designed to investigate genetic pathways that might be activated in heart transplant biopsies with QL. Methods: Nine heart allograft biopsies from one institution were included in the study. Tissue was stained for H/E and biopsies separated as having QL (5) vs. no QL (4). Total RNA was then extracted from FFPE. RNA extraction and gene analysis was performed using the Nanostring n-Counter Human Organ Transplant Immunology Panel (Seattle, WA). Results: The heat map ( Figure 1) shows a clear separation between biopsies with QL and biopsies without QL. Pathways that were upregulated in biopsies with QL included: NK-kappa Beta, cytokine signaling, chemokine signaling, cytotoxicity, type II interferon, Toll-like receptor, B-cell receptor, T-cell checkpoint, lymphocyte trafficking, oxidative stress, MAPK, Class II Ag presentation, complement system, Class I antigen presentation, TNF family, NLR family, cell cycle regulation, mTOR, inflammasomes, TGF-beta, epigenetics and transcription, T-reg differentiation, Th1 differentiation, Th2 differentiation, Th17 differentiation, cytosolic DNS sensing, innate immune system, adaptive immune system, hematopoiesis, T-cell receptor signaling, cell-ECM interaction. In contrast, the following pathways were downregulated in biopsies with QL: autophagy, angiogenesis, tissue homeostasis. Biopsies with QL showed a predominance of adaptive type Th2 response over Th1genes (3.88x vs. 3.15x). Individual regulatory genes (all p< 0.001) that were higher in biopsies with QL included TGFbeta1, IL10RA, Foxp3 and JAK3. Conclusion: Heart allograft biopsies with QL showed a clearly differential expression of genes compared to biopsies without QL. Pathways and individual upregulated genes suggest a shift towards regulation and acceptance of the allograft. QL, far from being passive bystanders, may have a positive immunomodulatory function in cardiac allografts.

Alloimmune Response After SARS-CoV-2 Vaccination in Lung Transplant T. Sam, 1 M. Askar, 2 C. Naik, 3 K. Vandervest, 3 R. Rosenblatt, 3 T. Grazia, 3 and S. Mathai. 4 1 Pharmacy, Baylor Univ Medical Center, Dallas, TX; 

Only 3 patients (5.5%) developed dnDSA after vaccination; all were S-IgG positive. One had history of antibody mediated rejection (AMR), while another was initially negative for dnDSA at 6 weeks post-vaccination, but turned positive at 7 months (low level Class II DSA). One patient who had prior DSA developed clinical rejection (AMR) with Class II dnDSA (DR7) and significant rise in prior DSA (DR53, DQ2) to >20,000 MFI at 6 months (negative at 3 months) post-vaccine in the setting of new viral infection. Another patient was excluded from this study as he died of AMR and dnClass II DSA (DQ8 > 10,000 MFI, DQ6, DR4 within 5 days of dose) 2 months after his first Pfizer/BioNTech dose, but before 3 month S-IgG testing. Conclusion: In our cohort, dnDSA after SARS-CoV-2 vaccination was uncommon but observed in patients who developed S-IgG response. The single AMR case occurred late and may be related to infection

Kidney Transplantation in Single Ventricle Palliated Patients: A Pediatric Cardiac Care Consortium Study S.R. Deshpande, 1 J. Claxton, 2 and L. Kochilas. 3 1 Pediatric Cardiology, Children's National Hospital