Challenges to Transplantation by the Assault of CoVid-19: Emergence of Molecular Diagnostics as Surveillance
Medical / Scientific Consultant, LLC, USA
Medical Director, Transplant Molecular Diagnostics, CareDX, Inc. USA
Received: March 27, 2020 | Accepted: March 29 , 2020 | Published: March 31, 2020
OBM Transplantation 2020, Volume 4, Issue 1, doi:10.21926/obm.transplant.2001106
Recommended citation: Ross DJ. Challenges to Transplantation by the Assault of CoVid-19: Emergence of. OBM Transplantation 2020;4(1):3; doi:10.21926/obm.transplant.2001106.
© 2020 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
In the midst of a devastating SARS-CoVid-2 (CoVid-19) pandemic, significant challenges have presented to the field of solid organ transplantation . The potential for donor viral transmission and/or post-transplant infection are looming threats to clinical outcomes as well as instilling a sense of angst that permeate the transplant community. Further, the ethical dilemma inevitably has surfaced – whether to proceed with transplant while institutions face dwindling available medical resources for ventilators, critical care nursing staff and beds. Indeed, mounting adversity now only compounds uncertainty as related to transplant center “wait list times” and mortality. Regardless, during such times of tribulation, innovative thought emerges that may challenge the existing status quo. Concern mounts regarding the appropriateness of established programmatic protocols for invasive allograft biopsy procedures and regimented medical specialty clinic appointments as surveillance. Alternatively, could these be decreased or omitted altogether during implementation of laboratory biomarker and telemedicine surveillance and thereby lessen patient contagion exposures? To this end, significant advances in biomarker allograft surveillance now exist in our armamentarium - “Gene Expression Profiling” (GEP) [AlloMap®] in peripheral blood mononuclear cells for assessment of cardiac allograft quiescence or rejection [2,3,4] and biomarkers representing “allograft injury” such as donor-derived cell-free DNA (dd-cfDNA) [AlloSure®] [5,6,7,8,9,10,11,12] after renal, cardiac and lung transplantation that provide further insights. Indeed, novel validated composite biomarker panels that incorporate GEP, cfDNA, and chemokine proteomics have recently emerged within the clinical arena and have potential for further expanding our biomarker surveillance repertoire . Therefore, our traditional clinical protocols may and probably should be challenged in light of the present global pandemic that severely impacts the field of organ transplantation. In the immortal words of Winston Churchill - “To improve is to change. To be perfect is to change often.”
David J. Ross was the sole author.
The author has declared that no competing interests exist.
- Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med. 2020. [CrossRef]
- Crespo-Leiro MG, Stypmann J, Schulz U, Zuckermann A, Mohacsi P, Bara C, et al. Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II. Eur Heart J. 2016; 37: 2591-2601. [CrossRef]
- Deng MC, Elashoff B, Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, et al. Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients. Transplantation. 2014; 97: 708-714. [CrossRef]
- Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010; 362: 1890-1900. [CrossRef]
- De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014; 6: 241ra277. [CrossRef]
- Gielis EM, Ledeganck KJ, Dendooven A, Meysman P, Beirnaert C, Laukens K, et al. The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation. Nephrol Dial Transplant. 2019. [CrossRef]
- Grskovic M, Hiller DJ, Eubank LA, Sninsky JJ, Christopherson C, Collins JP, et al. Validation of a clinical-grade assay to measure donor-derived cell-free DNA in solid organ transplant recipients. J Mol Diagn. 2016; 18: 890-902. [CrossRef]
- Jordan SC, Bunnapradist S, Bromberg JS, Langone AJ, Hiller D, Yee JP, et al. Donor-derived cell-free DNA identifies antibody-mediated rejection in donor specific antibody positive kidney transplant recipients. Transplant Direct. 2018; 4: e379. [CrossRef]
- Khush KK, Patel J, Pinney S, Kao A, Alharethi R, DePasquale E, et al. Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study. Am J Transplant. 2019; 19: 2889-2899. [CrossRef]
- Stites E, Kumar D, Olaitan O, Swanson SJ, Leca N, Weir M, et al. High levels of dd-cfDNA identifies patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury. Am J Transplant. 2020. [CrossRef]
- Agbor-Enoh S, Wang Y, Tunc I, Jang MK, Davis A, De Vlaminck I, et al. Donor-derived cell-free DNA predicts allograft failure and mortality after lung transplantation. EBioMedicine. 2019; 40: 541-553. [CrossRef]
- Agbor-Enoh S, Jackson AM, Tunc I, Berry GJ, Cochrane A, Grimm D, et al. Late manifestation of alloantibody-associated injury and clinical pulmonary antibody-mediated rejection: Evidence from cell-free DNA analysis. J Heart Lung Transplant. 2018; 37: 925-932. [CrossRef]
- Yang JYC, Sarwal RD, Sigdel TK, Damm I, Rosenbaum B, Liberto JM, et al. A urine score for noninvasive accurate diagnosis and prediction of kidney transplant rejection. Sci Transl Med. 2020; 12. [CrossRef]