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Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection
PURPOSE: A link between SARS-CoV2 infection and myocardial injury has been described. Our center utilizes non-invasive surveillance with gene expression profiling and donor-derived cell-free DNA (dd-cfDNA) in heart transplant (HTx) patients who are either stable or in whom invasive surveillance is c...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Published by Elsevier Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988548/ http://dx.doi.org/10.1016/j.healun.2022.01.277 |
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author | Kamath, M. Shekhtman, G. Grogan, T. Hickey, M.J. Silacheva, I. Shah, K.S. Shah, K.S. Hairapetian, A. Gonzalez, D. Godoy, G. Hsu, J. Bakir, M. Reed, E.F. Elashoff, D. Bondar, G. Deng, M.C. |
author_facet | Kamath, M. Shekhtman, G. Grogan, T. Hickey, M.J. Silacheva, I. Shah, K.S. Shah, K.S. Hairapetian, A. Gonzalez, D. Godoy, G. Hsu, J. Bakir, M. Reed, E.F. Elashoff, D. Bondar, G. Deng, M.C. |
author_sort | Kamath, M. |
collection | PubMed |
description | PURPOSE: A link between SARS-CoV2 infection and myocardial injury has been described. Our center utilizes non-invasive surveillance with gene expression profiling and donor-derived cell-free DNA (dd-cfDNA) in heart transplant (HTx) patients who are either stable or in whom invasive surveillance is contraindicated. We evaluated whether HTx recipients diagnosed with SARS-CoV2 infection demonstrated evidence of myocardial allograft injury using dd-cfDNA. METHODS: HTx recipients were included if they had dd-cfDNA testing (AlloSure; CareDx Inc., Brisbane, CA) within 60 days of their initial SARS-CoV2 diagnosis. Data on hospitalization, therapy, and clinical outcomes was captured. Dd-cfDNA results at the assay limit of detection (LOD, <0.12%) were set equal to the LOD. RESULTS: Between 3/2020 and 6/2021, we identified 12 HTx recipients with SARS-CoV2 and dd-cfDNA results within the specified time period; median age was 55 (IQR 28 - 64.5) with infection occurring 506.5 days (IQR 176 - 803.5) after transplant. Mean dd-cfDNA was 0.13 ± 0.03%, assessed 26 (IQR 20 - 35) days after infection. Prior results, available for 9 patients and obtained a median of 33 (IQR 27 - 59) days prior to infection, did not differ from post-infection values (0.13 ± 0.02%, p = 0.66). Following diagnosis, 8 (67%) patients were hospitalized; 5 had mycophenolate held, 2 received steroids, 2 received convalescent plasma, 4 received remdesivir, and 1 received monoclonal Ab therapy. At a median follow-up time of 304 (IQR 212.5 - 331) days after diagnosis, all twelve patients were alive with good allograft function (mean ejection fraction 59 ± 4.8%); interval clinically-relevant immunologic outcomes included one episode of rejection (pAMR1) and three (25%) findings of de novo donor-specific antibodies (dnDSA). CONCLUSION: In this single-center pilot study assessing myocardial injury among HTx recipients within 2 months of SARS-CoV2 infection, the majority of patients had low dd-cfDNA results (<0.15%) and demonstrated good intermediate-term (6-12 months) graft function. While limited by sample size and protocol-based inclusion criteria, our findings suggest that sustained myocardial injury in HTx recipients after SARS-CoV2 infection may not be common. The impact of SARS-CoV2 infection on immunologic outcomes including rejection and dnDSA in this population merit further study. |
format | Online Article Text |
id | pubmed-8988548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Published by Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89885482022-04-11 Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection Kamath, M. Shekhtman, G. Grogan, T. Hickey, M.J. Silacheva, I. Shah, K.S. Shah, K.S. Hairapetian, A. Gonzalez, D. Godoy, G. Hsu, J. Bakir, M. Reed, E.F. Elashoff, D. Bondar, G. Deng, M.C. J Heart Lung Transplant (256) PURPOSE: A link between SARS-CoV2 infection and myocardial injury has been described. Our center utilizes non-invasive surveillance with gene expression profiling and donor-derived cell-free DNA (dd-cfDNA) in heart transplant (HTx) patients who are either stable or in whom invasive surveillance is contraindicated. We evaluated whether HTx recipients diagnosed with SARS-CoV2 infection demonstrated evidence of myocardial allograft injury using dd-cfDNA. METHODS: HTx recipients were included if they had dd-cfDNA testing (AlloSure; CareDx Inc., Brisbane, CA) within 60 days of their initial SARS-CoV2 diagnosis. Data on hospitalization, therapy, and clinical outcomes was captured. Dd-cfDNA results at the assay limit of detection (LOD, <0.12%) were set equal to the LOD. RESULTS: Between 3/2020 and 6/2021, we identified 12 HTx recipients with SARS-CoV2 and dd-cfDNA results within the specified time period; median age was 55 (IQR 28 - 64.5) with infection occurring 506.5 days (IQR 176 - 803.5) after transplant. Mean dd-cfDNA was 0.13 ± 0.03%, assessed 26 (IQR 20 - 35) days after infection. Prior results, available for 9 patients and obtained a median of 33 (IQR 27 - 59) days prior to infection, did not differ from post-infection values (0.13 ± 0.02%, p = 0.66). Following diagnosis, 8 (67%) patients were hospitalized; 5 had mycophenolate held, 2 received steroids, 2 received convalescent plasma, 4 received remdesivir, and 1 received monoclonal Ab therapy. At a median follow-up time of 304 (IQR 212.5 - 331) days after diagnosis, all twelve patients were alive with good allograft function (mean ejection fraction 59 ± 4.8%); interval clinically-relevant immunologic outcomes included one episode of rejection (pAMR1) and three (25%) findings of de novo donor-specific antibodies (dnDSA). CONCLUSION: In this single-center pilot study assessing myocardial injury among HTx recipients within 2 months of SARS-CoV2 infection, the majority of patients had low dd-cfDNA results (<0.15%) and demonstrated good intermediate-term (6-12 months) graft function. While limited by sample size and protocol-based inclusion criteria, our findings suggest that sustained myocardial injury in HTx recipients after SARS-CoV2 infection may not be common. The impact of SARS-CoV2 infection on immunologic outcomes including rejection and dnDSA in this population merit further study. Published by Elsevier Inc. 2022-04 2022-04-07 /pmc/articles/PMC8988548/ http://dx.doi.org/10.1016/j.healun.2022.01.277 Text en Copyright © 2022 Published by Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | (256) Kamath, M. Shekhtman, G. Grogan, T. Hickey, M.J. Silacheva, I. Shah, K.S. Shah, K.S. Hairapetian, A. Gonzalez, D. Godoy, G. Hsu, J. Bakir, M. Reed, E.F. Elashoff, D. Bondar, G. Deng, M.C. Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection |
title | Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection |
title_full | Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection |
title_fullStr | Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection |
title_full_unstemmed | Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection |
title_short | Using Donor-Derived Cell-Free DNA for Assessment of Myocardial Injury in Heart Transplant Recipients After SARS-CoV2 Infection |
title_sort | using donor-derived cell-free dna for assessment of myocardial injury in heart transplant recipients after sars-cov2 infection |
topic | (256) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988548/ http://dx.doi.org/10.1016/j.healun.2022.01.277 |
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