Impact of COVID-19 in solid organ transplant recipients

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exploded onto the world stage in early 2020. The impact on solid organ transplantation (SOT) has been profound affecting potential donors, candidates, and recipients. Importantly, decreased donations and the pressure of limited resources placed on health care by the pandemic also disrupted transplant systems. We address the impact of COVID-19 on organ transplantation globally and review current understanding of the epidemiology, outcomes, diagnosis, and treatment of COVID-19 in SOT recipients.     

The impact of COVID-19 on kidney transplantation and the kidney transplant recipient – One year into the pandemic

The COVID-19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses on the impact of COVID-19 on kidney transplantation rates, mortality, policy decisions, and the clinical management of transplanted patients infected with COVID-19.     

COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients

The COVID-19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased susceptibility and worsened outcomes of COVID-19 in immunosuppressed recipients. The consequences of COVID-19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID-19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID-19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID-19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID-19.     

Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.     

Impact of Covid-19 on kidney transplant and waiting list patients: Lessons from the first wave of the pandemic

BackgroundThe first wave of the Covid-19 pandemic resulted in a drastic reduction in kidney transplantation and a profound change in transplant care in France. It is critical for kidney transplant centers to understand the behaviors, concerns and wishes of transplant recipients and waiting list candidates.MethodsFrench kidney patients were contacted to answer an online electronic survey at the end of the lockdown.ResultsAt the end of the first wave of the pandemic in France (11 May 2020), 2112 kidney transplant recipients and 487 candidates answered the survey. More candidates than recipients left their home during the lockdown, mainly for health care (80.1% vs. 69.4%; P < 0.001). More candidates than recipients reported being exposed to Covid-19 patients (2.7% vs. 1.2%; P = 0.006). Many recipients and even more candidates felt inadequately informed by their transplant center during the pandemic (19.6% vs. 54%; P < 0.001). Among candidates, 71.1% preferred to undergo transplant as soon as possible, 19.5% preferred to wait until Covid-19 had left their community, and 9.4% were not sure what to do.ConclusionsDuring the Covid-19 pandemic in France, the majority of candidates wished to receive a transplant as soon as possible without waiting until Covid-19 had left their community. Communication between kidney transplant centers and patients must be improved to better understand and serve patients’ needs.     

Evolving Impact of COVID-19 on Transplant Center Practices and Policies in the United States

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19–positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.     

肺移植全球发展概况与展望

在2020年至2021年新型冠状病毒肺炎（新冠肺炎）疫情流行期间,全球肺移植进入新发展阶段。全球范围内,上报国际心肺移植学会（ISHLT）的肺移植数据已经超过70 000例。肺移植供者和受者特征、儿童肺移植受者的适应证随着时间和医疗技术的发展,发生了巨大的变化。肺移植在新冠肺炎相关急性呼吸窘迫综合征（ARDS）患者中的治疗也受到全球瞩目。肺移植外科技术不断发展,也将与更多的新技术融合,在人工肺脏和异种移植领域获得新的突破。本文总结了全球肺移植供、受者特征研究的最新进展,并进一步展望未来发展的趋势,以期终末期肺病患者能够从肺移植技术发展中得到更多获益。     

Immediate impact of COVID-19 on transplant activity in the Netherlands

The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with transplantation, the attributable risk of immunosuppression for COVID-19 and entrenched health care resources and capacity. The transplant community is faced with choosing a lesser of two evils: initiating immunosuppression and potentially accepting detrimental outcome when transplant recipients develop COVID-19 versus postponing transplantation and accepting associated waitlist mortality. Notably, prioritization of health care services for COVID-19 care raises concerns about allocation of resources to deliver care for transplant patients who might otherwise have excellent 1-year and 10-year survival rates. Children and young adults with end-stage organ disease in particular seem more disadvantaged by withholding transplantation because of capacity issues than from medical consequences of SARS-CoV-2. This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs.     

居家肾移植受者新型冠状病毒肺炎知信行调查及影响因素分析

目的调查居家肾移植受者对新型冠状病毒肺炎(COVID-19)的认知、态度和行为现状,并分析其影响因素。 方法对树兰(杭州)医院随访信息系统中2018年4月至2019年12月接受肾移植的受者进行整群调查。调查问卷包含两部分：(1)受者一般资料,包括性别、年龄、肾移植术后时间、受教育程度和居住地等;(2)COVID-19知信行部分包含3个维度共计25个条目,内容包括对COVID-19的认知和态度以及个人防护措施,各条目均应用Likert 4级评分法。收集纳入受者的临床信息,采用在线问卷调查平台和电话两种方式进行调查。采用t检验或方差分析比较不同性别、年龄、受教育程度、术后时间以及居住地的受者COVID-19知信行3个维度得分和总分;采用多元线性回归进行影响知信行总分的多因素分析。 结果共收到问卷245份,其中电话调查52例,使用在线问卷调查平台193例;有效问卷239份,有效率97.55%。239例肾移植受者COVID-19知信行总分为(81.2±8.1)分,其中知识、态度和行为维度得分分别为(32.3±4.5)、(21.9±1.8)和(26.9±3.6)分。单因素分析结果显示,年龄、受教育程度和居住地不同的肾移植受者知识维度得分差异均有统计学意义(P均<0.05);受教育程度、术后时间和居住地不同的肾移植受者态度维度得分差异均有统计学意义(P均<0.05);居住地不同的肾移植受者行为得分差异有统计学意义(P<0.05)。多因素分析结果显示,居住地是肾移植受者COVID-19知信行总分的影响因素(P<0.05)。 结论在COVID-19疫情期间,肾移植中心需有针对性的加强随访力度、方向以及增加健康教育的方式方法,重点关注老年、受教育程度较低以及居住在农村的肾移植受者。     

Solid Organ Transplantation After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective,Multicenter Study of the EBMT

To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984 and 2007 in Europe. Forty‐five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2‐year‐incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft‐versus‐host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence for underlying malignant diseases was 4% at 5 years (95% CI, 0% to 12%). In summary, this study shows that selected patients receiving SOT after HSCT have a remarkably good overall and organ survival. These data indicate that SOT should be considered in selected patients with single organ failure after HSCT.     

Heart transplantation in the early phase of the COVID-19 pandemic: A single-center case series

The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.     

Pediatric Transplantation in the United States, 1995–2004

This article reviews trends in pediatric solid organ transplantation over the last decade, as reflected in OPTN/SRTR data. In 2004, children younger than 18 years made up nearly 3% of the 86 378 candidates for organ transplantation and nearly 7% of the 27 031 organ transplant recipients. Children accounted for nearly 14% of the 7152 deceased organ donors. The transplant community recognizes important differences between pediatric and adult organ transplant recipients, including different etiologies of organ failure, surgical procedures that are more complex or technically challenging, effects of development on the pharmacokinetic properties of common immunosuppressants, unique immunological aspects of transplant in the developing immune system and increased susceptibility to posttransplant complications, particularly infectious diseases. For these reasons, and because of the impact of end-stage organ failure on growth and development, the transplant community has generally provided pediatric candidates with special consideration in the allocation of deceased donor organs. Outcomes following kidney, liver and heart transplantation in children often rank among the best. This article emphasizes that the prospects for solid organ transplantation in children, especially those aged 1–10 years are excellent. It also identifies themes warranting further consideration, including organ availability, adolescent survival and challenges facing pediatric transplant clinical research.     

COVID-19 in transplant recipients: The Spanish experience

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).     

后疫情时代的肺移植临床研究发展和未来展望

肺移植技术在全球经历了近半个世纪的发展,在中国也高速发展了二十余年,中国肺移植逐渐融入国际肺移植大家庭。2020年新型冠状病毒肺炎(新冠肺炎)疫情暴发,既是对中国肺移植发展的挑战,也使得全球同行关注中国肺移植发展,加速了国际间的交流与合作。随着对新冠肺炎重症患者肺移植的临床和基础研究逐步深入,移植科医师对于未来中国肺移植在供者的维护、高龄和儿童受者的选择、围手术期管理等方面有了更多的认知和思考。对于肺移植相关学科交叉领域的研究,需要开展设计优良、多方协作的临床试验,不断推进学科理论和实践的创新。     

Health-related quality of life,uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.     

Pediatric transplantation, 1994–2003

This article uses OPTN/SRTR data to review trends in pediatric transplantation over the last decade. In 2003, children younger than 18 made up 3% of the 82,885 candidates for organ transplantation and 7% of the 25,469 organ transplant recipients. Children accounted for 14% of the 6,455 deceased organ donors. Pediatric organ transplant recipients differ from their adult counterparts in several important aspects, including the underlying etiology of organ failure, the complexity of the surgical procedures, the pharmacokinetic properties of common immunosuppressants, the immune response following transplantation, the number and degree of comorbid conditions, and the susceptibility to post-transplant complications, especially infectious diseases. Specialized pediatric organ transplant programs have been developed to address these special problems, The transplant community has responded to the particular needs of children and has provided them special consideration in the allocation of deceased donor organs. As a result of these programs and protocols, children are now frequently the most successful recipients of organ transplantation; their outcomes following kidney, liver, and heart transplantation rank among the best. This article demonstrates that substantial improvement is needed in several areas: adolescent outcomes, outcomes following intestine transplants, and waiting list mortality among pediatric heart and lung candidates,     

Comparable renal graft survival in African-American and Caucasian recipients

In past years, many pediatric transplant centers found African-American renal transplant recipients to have poor graft survival. Since 1991 anti-lymphocyte induction therapy has been routinely used for pediatric cadaveric (CAD) and living-related donor (LRD) renal allograft recipients at the University of Tennessee, Memphis. Sixteen African-American first renal allograft recipients received induction therapy: 11 CAD allografts (10 OKT3, 1 ATGAM) and five LRD (all ATGAM). Sixteen Caucasian recipients received induction therapy; 3 CAD (all OKT3), 1 living-unrelated donor (OKT3), and 12 LRD (9 ATGAM, 3 OKT3). Mean age at renal transplantation was 11.8 and 10.5 years for African-American and Caucasian recipients, respectively. Predicted graft survival (PGS) estimated by the Kaplan-Meier method for the African-American patients was 94% at both 1 and 3 years, and for Caucasian patients was 94% and 85% at 1 and 3 years, respectively. Eleven African-American CAD recipients had a PGS of 91% at 1 and 3 years. Renal allograft survival for African-American and Caucasian pediatric recipients at our center appears to be comparable. This could be due, in part, to the use of anti-lymphocyte induction therapy. However, other factors, such as improved compliance or better immunological and pharmacological monitoring, may also have contributed. Received April 18, 1997; received in revised form January 14, 1998; accepted January 19, 1998     

The impact of the COVID-19 pandemic on pediatric firearm injuries in Colorado

BackgroundIn 2019 firearm injuries surpassed automobile-related injuries as the leading cause of pediatric death in Colorado. In the spring of 2020, the COVID-19 pandemic led to community-level social, economic, and health impacts as well as changes to injury epidemiology. Thus, we sought to determine the impact of the COVID-19 pandemic on pediatric firearm injuries in Colorado.MethodsWe conducted a retrospective review of pediatric firearm injured patients (≤ 18-years-old) evaluated at three trauma centers in Colorado from 2018–2021. Patients were stratified into two groups based on the time of their firearm injury: pre- COVID injuries and post- COVID injuries. Group differences were examined using t-tests for continuous variables and Chi Squared or Fisher's exact tests for categorical variables.ResultsOverall, 343 firearm injuries occurred during the study period. There was a significant increase in firearm injuries as a proportion of overall pediatric ED trauma evaluations following the onset of the COVID-19 pandemic (pre COVID: 5.18/100 trauma evaluations; post COVID: 8.61/100 trauma evaluations, p<0.0001). Assaults were the most common injury intent seen both pre and post COVID (70.3% vs. 56.7%, respectively); however, unintentional injuries increased significantly from 10.3% to 22.5% (p = 0.004) following the onset of the pandemic. Additionally, the COVID-19 pandemic was associated with a 177% increase in unintentional injuries in adolescents.ConclusionPediatric firearm injuries, particularly unintentional injuries, increased significantly in Colorado following the onset of the COVID-19 pandemic. The substantial increase in unintentional injuries among adolescents highlights the necessity of multi-disciplinary approaches to limit or regulate their access to firearms.Level of EvidenceLevel III.Study TypeRetrospective.     

Navigating Kidney Transplantation in the Early Phase of Coronavirus Disease 2019: Screening Patients With Reverse Transcriptase Polymerase Chain Reaction and Low-Radiation-Dose Chest Computed Tomography

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic of 2020 changed organ transplantation. All elective cases at our institution were postponed for approximately 3 months. Centers for Medicare and Medicaid Services considers organ transplant surgery a Tier 3b case, along with other high acuity procedures, recommending no postponement. Our transplant program collaborated with our transplant infectious disease colleagues to create a protocol that would ensure both patient and staff safety during these unprecedented times.MethodsThe living donor program was electively placed on hold until we had the proper protocols in place. Preoperative COVID-19 testing was required for all recipients and living donors. All patients underwent a rapid nasopharyngeal swab test. After testing negative by nasopharyngeal swab, recipients also underwent a low-radiation-dose computed tomography scan to rule out any radiographic changes suggestive of a COVID-19 infection.ResultsWe performed 8 living donor and 9 deceased donor kidney transplants. In comparison, we performed 10 living donor and 4 deceased donor transplants during the same time period in the previous year. Our testing protocol enabled efficient use of all suitable organs offered during the viral pandemic. No recipients or living donors tested positive or developed COVID-19.ConclusionsCreation of a viral testing protocol, developed in conjunction with our infectious disease team, permitted kidney transplantation to be performed safely, and the number of deceased donor transplants increased considerably without adversely affecting our outcomes.