key: cord-319797-455ldhiy
authors: Kumar, Deepali; Manuel, Oriol; Natori, Yoichiro; Egawa, Hiroto; Grossi, Paolo; Han, Sang‐Hoon; Fernández‐Ruiz, Mario; Humar, Atul
title: COVID‐19: A global transplant perspective on successfully navigating a pandemic
date: 2020-04-12
journal: Am J Transplant
DOI: 10.1111/ajt.15876
sha: 
doc_id: 319797
cord_uid: 455ldhiy

The COVID‐19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID‐19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health‐care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID‐19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant‐related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.

Transplantation has become an established treatment for end-stage organ diseases and is a highly regulated field. There are several threats to transplantation but one particularly important threat is that of an emerging infectious disease. Since the 1980s, there have been several emerging viral diseases including HIV in the late 1980s/early 1990s, SARS-CoV, West Nile Virus, pandemic influenza A/H1N1, Zika, Ebola, and now pandemic COVID-19 caused by SARS-CoV-2.

For each of these threats, transplant programs have responded in a coordinated fashion by assessing the risk of donor transmission, assessing the severity of disease in the recipient, and recognizing the potential for transmission to health-care workers. [1] [2] [3] [4] [5] This knowledge has then been used to generate algorithms for donor screening, not using organs from potentially infected donors, and recipient management. Many of these emerging viruses have been manageable, sometimes only limited to certain geographic areas, and transplantation/donation has been able to adapt and continue to provide this life-saving therapy in a safe and effective manner. The current COVID-19 pandemic is unique and unprecedented in modern times.

It has crossed borders and infected >180 000 persons worldwide that we know of, with likely many more undiagnosed cases. It has been difficult to contain partly due to the contagious nature of the virus and mild illness in a majority of individuals. Nevertheless, the The COVID-19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID-19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health-care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID-19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant-related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.

clinical decision-making, clinical research/practice, donors and donation: donor-derived infections, infection and infectious agents -viral, infectious disease, organ transplantation in general emergence of COVID-19 has impacted transplantation worldwide.

The impact has not been just restricted to issues around donors or recipients, but also health-care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Based on our collective experience, we suggest mitigation strategies such as donor screening approaches, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to the management of immunosuppression trials during the pandemic, and the role of transplant infectious diseases and transplant societies for education and disseminating current information. We believe our collective experience will be valuable to the transplant community in the absence of hard published research findings this early in the pandemic.

There is a potential for COVID-19 to be transmitted by organ donation although the risk of this is unclear and we are not aware of any reports of transmission. The virus is primarily isolated from the respiratory tract suggesting the lung is a very high-risk for transmission when used from an infected donor. However, virus is also been reported to be isolated from the blood in up to 15% of cases and therefore, all organs may be at risk of acquisition. 6 With the SARS epidemic of 2003, autopsy data demonstrated virus in almost all organs including the liver, kidney, and intestines. 7 Donor screening from both a clinical and laboratory perspective is therefore an important consideration and has been the subject of much discussion. 8 In areas with significant community transmission, if organ donation is to proceed in a safe manner, the authors recommend that both clinical and rapid laboratory screening is required. This approach to donation may differ in countries depending on the degree of community-transmission of COVID-19. However, many areas have noted that due to limitations in test availability the true rate of community penetration may be unknown. During the SARS-CoV outbreak of 2003 in Toronto, a clinical donor screening tool was instituted, incorporating epidemiological and clinical features of the donor, which then allowed deceased-donor transplantation to continue. 2 However, unlike in 2003, there has been rapid development of nucleic acid testing (NAT) for SARS-CoV-2 and therefore, testing of nasopharyngeal specimens has been incorporated and is the cornerstone of donor screening algorithms in several jurisdictions. Realtime NP swab donor screening has been successfully deployed in organ procurement organizations (OPOs) within Canada, Italy, Spain, and South Korea. However, many questions remain, including the false negative rates of testing which can be due to inappropriate collection or a patient early in the incubation period. Since SARS-CoV-2 is known to use the ACE2 receptor for viral entry, a bronchoalveolar lavage (BAL) specimen may be more appropriate than naso/oropharyngeal swab. However, bronchoscopy would have the potential risk of aerosolization and may not be logistically feasible. For this approach to be successful, the test result must also be rapidly available. Laboratory-developed or commercial NAT testing needs to be made available to OPOs with results in hours. Ruling out COVID-19 in a donor is also essential for the safety of organ procurement teams. Shortages of testing kits, reagents, and laboratory resources to carry out donor screening in the midst of a pandemic are also a major consideration.

In Canada, we developed a COVID-19 donor clinical screening tool and also started NP swab NAT screening for COVID-19 ( Figure 1 ). For areas with significant community transmission, the tool could be modified to reduce the importance of travel history.

In the latter case, NAT testing would play a much larger role but the tool allows a second layer of redundancy in the screening process.

Collectively the authors have had experience with asymptomatic NAT positive donors.

In Switzerland, where virus is currently widely circulating in the community, we established universal screening for all deceased donors by NAT in NP swab or BAL on March 5, 2020 (Table 1) . Given the potential increase in risk for health personnel and current limited resources in the ICU for performing bronchoscopy, we favor NP swab over BAL for screening of SARS-CoV-2. Of note, given the wide clinical presentation of COVID-19, potential donors can be asymptomatic or mildly symptomatic at the time of donation, thus highlighting the need for universal screening.

In Italy, where there is significant community transmission, deceased donor screening with NAT for SARS-CoV-2 on BAL has become mandatory starting from February 23, 2020. At the time of this manuscript none of the screened donors has been found positive.

The main problem in Italy is the huge number of patients requiring mechanical ventilation and that many ICUs that have been transformed to COVID-19 ICUs. For this reason, the number of potential donors is expected to significantly decrease.

In Spain, with high community transmission, universal screening (through at least one NP specimen and, if feasible, one lower respiratory tract sample) is now mandatory for all lung and small bowel donors across the country. In addition, NAT screening is also required for any deceased donor with recent travel to or stay in selected highrisk Spanish regions, contact with a confirmed COVID-19 case, with a positive symptom screen. No donor-derived transmission has been reported to date.

The Japan Society for Transplantation (JST) published their formal statement on March 6, 2020 (http://www.asas.or.jp/jst/pdf/ info_20200 306.pdf) and recommended to clinically screen donors for significant exposure to COVID-19, travel history to high-risk countries, and symptoms including fever and respiratory symptoms. However, due to limited testing capacity, universal screening has not been adopted. 

In the face of a pandemic that may impact transplant recipients adversely, decisions to continue or cease transplantation need to be made by programs. Although donor transmission is an ominous possibility, many of these decisions are actually independent of donor transmission and have to do with the following considerations: pandemic. The other part of the decision is how much health-care resource is utilized by newly transplanted patients with regard to readmission rates and whether during a period of strained hospital resources, it would be appropriate to perform kidney transplantation. It has been suggested, that the risk of infection in the community for a newly transplanted recipient may be mitigated by either not using induction therapy or using an IL2 receptor antagonist for induction rather than polyclonal globulin induction. This is unknown but is a logical extension of data from other viral infections. Another possibility is to temporarily pause kidney transplantation but continue to transplant highly sensitized patients. This has been done in some jurisdictions. We suggest a phased approach to decreasing transplant activity ( Although it is difficult to determine the course of the pandemic, the majority of hypotheses are based on peak of disease lasting several months followed by a stable level with either year-round or seasonal circulation of the virus. At some point transplant programs that have decreased activity will need to ramp up. We suggest this could be done in a phased approach where more urgent transplants could proceed first, with more "elective" cases phased in later. This would need to be coupled with safe donation and transplant practices to prevent and treat COVID-19, as well as an understanding of local health resource limitations. darunavir-cobicistat, interferon beta and (hydroxy)chloroquine, as well as combinations of these therapies. Passive high-titer immunoglobulin from recovered COVID patients has been used.

Blunting the inflammatory response with a trial of corticosteroids is controversial. 9,10 However, reduction of IL-6 in critically ill patients with tocilizumab has also been attempted. 

We must think about steps to take care of ourselves and ensure we remain healthy so that we can look after our patients. Risks to think about include: (1) teams traveling for donor procurement to areas of high risk, (2) performing high-risk procedures such a bronchoscopies 

This is an exceptional time for the world full of uncertainty and anxiety. For those of us working in transplantation, it is especially worrisome given the highly vulnerable group of patients we serve. In this context it is of the utmost importance that we come together as a team, to share knowledge and experience that will benefit all of our program and most importantly our patients. 

Pandemic influenza and its implications for transplantation

Severe Acute Respiratory Syndrome (SARS) in a liver transplant recipient and guidelines for donor SARS screening

Considerations for screening live kidney donors for endemic infections: a viewpoint on the UNOS policy

Zika Virus in transplantation: emerging infection and opportunities

Ebola virus disease: implications for solid organ transplantation

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Emerging viral infections in transplant recipients

Coronavirus disease 2019: implications of emerging infections for transplantation

Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

COVID-19: A global transplant perspective on successfully navigating a pandemic