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In View: Special Review

Summary of International Recommendations for Donation and Transplantation Programs During the Coronavirus Disease Pandemic

Weiss, Matthew J. MD1,2,3,4; Lalani, Jehan MHA4; Patriquin-Stoner, Chelsea BA3; Dieudé, Mélanie PhD3,5; Hartell, David MA4; Hornby, Laura MSc3,4,6; Shemie, Sam D. MD4,3,7; Wilson, Lindsay MHA4; Mah, Allison MD8

Author Information
doi: 10.1097/TP.0000000000003520

Abstract

INTRODUCTION

The COVID-19 pandemic caused by the SARS-CoV-2 virus has disrupted nearly every aspect of global health care, and organ donation and transplantation (ODT) is no exception.1,2 As the pandemic spread, clinicians and ODT programs were forced to make difficult decisions based on very limited scientific evidence around issues such as the risk of donor to recipient transmission, when or if to suspend living or deceased donation programs, how to prevent infection in waitlisted or posttransplant patients, and how to manage infections that do occur.

Multiple groups have provided guidance on some of these questions including recommendations from national ODT governing bodies (eg, the Spanish Organización Nacional de Transplantes),3 international professional associations (eg, The Transplantation Society),4 and national professional societies (eg, the American Society of Transplant Surgeons).5 Working under very tight timelines, these recommendations were generated through expert consensus to provide advice during the critical phase of rapid spread of COVID-19. The Transplantation Society (TTS) collected links to many of these documents, facilitating ease of access to rapidly evolving practices across different geographic areas, which is available at: https://tts.org/index.php?option=com_content&view=article&id=692&Itemid=115.

These documents are important for administrators and clinicians, although they have limitations. The primary limitation is the lack of high-quality evidence to inform them. While the rate of publications related to the COVID-19 pandemic has expanded dramatically, the amount of high-quality literature in donation and transplantation remains limited. Some guidelines related to ODT topics have since been published in peer-reviewed forums, but at this point, no group has adhered to rigorous clinical practice guideline (CPG) methodology for generating rapid recommendations.6,7 These and other factors, including overburdened healthcare systems and time pressure to create recommendations for practice, have created challenges in adhering to practices such as broad stakeholder involvement or formal literature review.

With the goal of improving the value and rigor of COVID-19-related CPGs, Canadian Blood Services (CBS), the Canadian Donation and Transplant Research Program (CDTRP), and the Canadian Society of Transplantation (CST) created a CPG taskforce. Our first task was to understand existing recommendations. This manuscript is a brief report of the methods used and the categories of recommendations found, including an overview of some of the various recommendations made by respective organizations. This report is not intended to generate stand-alone guidelines, rather it serves as a communication and link to publicly available information as part of the ongoing review described herein.

MATERIALS AND METHODS

To facilitate comparison of recommendations, we created a publicly accessible website with existing recommendations grouped by topic area. To initially populate the website, we reviewed a convenience sample of 18 documents created by national bodies or professional associations governing ODT practice that were available as of May 19, 2020, on the TTS website (Appendix S1, SDC, http://links.lww.com/TP/C44). Statements within the documents were extracted, summarized, and grouped according to topic area.

Extraction was initially done by a single reviewer (MW) and then confirmed by additional reviewers who were trained in the process (reviewers listed in acknowledgments). Summaries were reviewed by senior authors (MW, AM) before inclusion on the website. Summaries and source material are available on the CDTRP website: https://cdtrp.ca/en/covid-19-international-recommendations-for-odt/

This process is ongoing. A formal search strategy has been created to monitor relevant published literature related to COVID-19 and ODT systems. Prospectively, we will update these summaries and the listed recommendations as documents are revised, and additional guidelines are identified.

This summary of published recommendations did not involve contact with patients or interviews with participants; thus, ethics approval was not requested.

RESULTS

Characteristics of the 18 reviewed documents are summarized in Table 1. Table 2 shows the categories of recommendations created during extraction. These include both deceased and living donation as well as logistic and provider safety issues. Each category was summarized, and an example of a summary is included in Box 1. Other summaries are not included here, as they are available on the website and are updated every 4–5 weeks.

TABLE 1. - Characteristics of guidance documents reviewed
Document characteristics umber of documents
Organization type
 National donation or transplant governing body 6
 International donation or transplant society 4
 National donation and transplant society 3
 Other (includes joint recommendations) 5
Region
 International 3
 North America 5
 Europe 8
 Asia 1
 Australasia 1
Language
 English 17
 French 1

TABLE 2. - Topics and sub-topics of COVID-19 recommendations
COVID-19 screening of potential deceased donors
− Screening recommendations for potential donors
− Testing recommendations
− Donation from patients with positive or inconclusive testing
− Exclusion of potential donors
− Acceptance of organs offered from other countries
− Testing regime for documenting clearance of confirmed cases
− Avoidance of recovery from donors with endemic/high prevalence areas
Exposure assessment and recipient screening recommendations
− Screening and testing
− Exposure and eligibility
Post-transplant risk
− Immunomodulation and treatment post-transplant
− Risk of acquisition
− Prevention and control
Deceased donation recommendations
− Suspension of transplant activity
− Deceased kidney/pancreas
− Deceased liver
− Deceased heart
− Deceased lung
Living donation/paired donation recommendation
− Screening recommendations for potential donors
− Testing recommendations
− Exclusion of potential donors
Organ donation and transplant professionals’ personal protective equipment (PPE) use
Additional recommendations
− Ethics and consent
− Logistics concerns
− Waitlist patients

While recommendations were often similar, there was broad variability regarding both the topics addressed in each document and the specifics of how each topic was addressed. Frequently, organizations did not address the full spectrum of issues but instead focused on aspects such as a screening or treatment strategies post-transplant. When specific issues were broadly addressed, there was often agreement on a general concept, such as the need to perform laboratory testing for COVID-19, but specific recommendations differed. Nasopharyngeal polymerase chain reaction (PCR) testing was the most frequently recommended (61%), although other methods such as oropharyngeal PCR (43%) or bronchial secretion PCR (24%) were also recommended either in addition to or in place of nasopharyngeal swab testing. Four documents commented on computed tomography (CT) scans for asymptomatic potential donors, with one document (Belgian Transplant Society) recommending its use for all potential donors.

Organizations were similarly variable in recommendations on the management of patients who are potential donors but had previous documented COVID-19 infections. Waiting periods after resolution of symptoms varied from 14 to 28 days. Most, but not all, groups specifically recommended repeat testing after symptom resolution, with some requiring a single negative test and other two negative tests.

DISCUSSION

In performing this review of available recommendations related to ODT in the COVID-19 era, we discovered multiple points of convergence and divergence. Topics ranged from testing recommendations to screening of potential deceased donors, to the usage of personal protective equipment for ODT professionals, and suspension of transplant activity. While there was often broad but not universal consensus across documents (eg, excluding potential donors with documented COVID-19 infection), recommendations on some points varied, including the use of thoracic CT-scans for asymptomatic potential donors, the recommended time and testing requirements before recovering organs from a previously infected donor, and alteration of immunosuppressive therapy if a transplant recipient becomes COVID-19 positive.

Collating and summarizing these recommendations highlight which issues were addressed, and thus, what topics merited attention from the various bodies that created these recommendations. The website allows stakeholders to rapidly compare their practices with those of the international community. While this places substantial emphasis on expert opinion, until further high-quality studies are performed in these fields, it is acknowledged that most guidance will come from consensus expert opinion.

BOX 1. Summary of recommendations related to immunomodulation and treatment posttransplant

There is limited guidance related to lymphocyte depleting therapy by societies suggesting a reduction in the use of lymphocyte depleting therapy during the pandemic. Regarding maintenance immunosuppression, the general recommendation from available guidance is to not reduce maintenance immunosuppression in asymptomatic transplant recipients. In the setting of recipients with COVID-19, it is recommended to consider reduction of immunosuppression with most societies suggesting starting with an adjustment to antimetabolite. This decision should be made in conjunction with the transplant team and should not be self-managed by recipients.

Societies do not comment or recommend against prophylactic anti-SARS-CoV-2 therapy at this time. Regarding therapeutic antivirals, the National Health Service in the UK recommends potential use within a clinical trial, whereas the American Association For the Study of Liver Diseases (AASLD) recommends the use of Remdesivir. Due to drug-to-drug interaction considerations, lopinavir-ritonavir is not favored by United Network for Organ Sharing or AASLD in transplant recipients.

The strength of this process is that we were able to establish the breadth of challenges addressed by a sample of global ODT bodies. Since the goal is to use these recommendations to ensure that areas of interest are addressed in our development of CPGs, this minimizes gaps that might have occurred if our questions had been determined only by discussion with national experts. By creating a dynamic platform to update summaries, we have generated a resource that can be used by other organizations who may be creating or modifying recommendations. The primary limitation is the convenience nature of the initial documents reviewed. Due to time and resource constraints, we prioritized development of a platform that could be updated rather than ensuring every possible recommendation was included in the first iteration of this process. Similarly, included guidelines were limited to those with English and French versions available due to limited translation capacity. This may exclude important country-level perspectives of particularly hard-hit regions such as Italy, Germany, and China.

Beyond creation of a website summarizing existing guidance, the ultimate goal of this project is to create rigorous and frequently updated CPGs. The results of the process described above, coupled with input from stakeholders, have informed selection of the PICO (population, intervention, control, outcome) questions we will address in our CPG development. We have created working groups consistent with the topic areas identified in Table 2 and, based on broad stakeholder input, have prioritized working groups related to treatment and prevention of COVID-19 in transplant recipients, screening of patients who are potential donors, and ethical and legal considerations. Literature searches based on PICO questions have been developed, and one working group, recipient protection, and treatment have generated preliminary recommendations, using accelerated, standard guideline development methodology.6,7 We plan to disseminate these recommendations and those on donor screening and ethical considerations by year end. In doing so, we hope to offer the donation and transplantation community recommendations based on a rigorous evaluation of the existing data, limited although that data might be. Besides offering guidance to clinicians in practice, doing so will also identify urgent gaps in our understanding of how COVID-19 impacts donation and transplantation. These gaps will serve as markers for the clinician scientists seeking out to prioritize questions to answer as we navigate this ongoing pandemic.

Looking beyond the current pandemic, this work creates opportunities for the international ODT community to expand collaborations in CPG generation. CPG creation is resource intensive and often involves multiple groups searching and summarizing the same pool of literature. By creating a framework to quickly respond to emerging issues, we hope to use this experience to create a durable platform for future international collaboration focused on addressing questions of importance to the global ODT community.

ACKNOWLEDGMENTS

We would like to extend a special thank you to the following individuals for their support with data extraction: Fatima Dharsee (BASc), Kyle Maru (MA), Christina Parsons (BSc), Canadian Blood Services; Minal Borkar-Tipathi (PhD), Mackenzie Cullip, Hyunyun Kim (MSc), Shanshan Lan (MD), Daniela Massierer (PhD), Alissa Rutman (BSc), Christine Wardell (MSc), Lauren Westhaver (BSc), Canadian Donation and Transplantation Research Program.

REFERENCES

1. Reddy MS, Hakeem AR, Klair T, et al. Trinational study exploring the early impact of the COVID-19 pandemic on organ donation and liver transplantation at national and unit levels. Transplantation. 2020;104:2234–2243.
2. Cannavò A, Passamonti SM, Martinuzzi D, et al. The impact of COVID-19 on solid organ donation: the North Italy Transplant Program Experience. Transplant Proc. [Epub ahead of print June 2020]. doi: 10.1016/j.transproceed.2020.06.025
3. Spanish recommendations to manage organ donation and transplantation regarding the infection associated with the new coronovirus (Sars-Cov-2) producer of Covid-19. Organización Nacional de Trasplantes. April 13, 2020. Available at https://content.tts.org/content/covid19/COVID-19-Summary-of-Spanish-recommendations-on-organ-donation-and-transplantation20200413.pdf. Accessed April 15, 2020.
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6. Rapid responses in the context of Covid-19: drafting method. Haute Autorité de Santé. April 2, 2020. Available at https://www.has-sante.fr/jcms/p_3168771/en/methode-d-elaboration-des-reponses-rapides-dans-le-cadre-du-covid-19. Accessed April 15, 2020.
7. Morgan RL, Florez I, Falavigna M, et al. Development of rapid guidelines: 3. GIN-McMaster Guideline Development Checklist extension for rapid recommendations. Health Res Policy Syst. 2018;16:63

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