The tools in our armamentarium to prevent the transmission of coronavirus disease 2019, known as COVID-19, are social distancing; frequent handwashing; use of facial masks; preventing nonessential contacts/travel; nationwide lockdown; and testing, isolation, and contact tracing. However, the World Health Organization’s suggestions to isolate, test, treat, and trace contacts are difficult to implement in the resource-limited developing world. The points to weigh before performing deceased-donor organ transplant in developing countries are as follows: limitations in standard personal protective equipment (as approved by the World Health Organization), testing kits, asymptomatic infections, negative-pressure isolation rooms, intensive care unit beds, ventilator support, telehealth, availability of trained health care workers, hospital beds, the changing dynamic of this pandemic, the unwillingness of recipients, education updates, and additional burdens on the existing health care system. This pandemic has created ethical dilemmas on how to prioritize the use of our facilities, equipment, and supplies in the cash-strapped developing world. We believe that, at the present time, we should aim to resolve the COVID-19 pandemic that is affecting a large sector of the population by diverting efforts from deceased-donor organ transplant. Transplant units should conduct case-by-case evaluations when assessing the convenience of carrying out lifesaving deceased-donor organ transplant, appropriately balanced with the resources needed to address the current pandemic.
Key words : COVID-19, Health care system, Medical ethics, Resources, Social distancing
Coronavirus disease 2019 (COVID-19) is a global pandemic, and cases are rising rapidly worldwide.1,2 As of April 19, 2020, there were approximately 2 331 099 global cases of COVID-19 including 160 952 deaths.1,2 The government of India’s Department of Health and Family Welfare reported 15 712 confirmed cases in India, including 2231 cured/discharged patients and 507 deaths.1 The current outbreak in India is unpredictable, as the curve has not yet reached its peak. If widespread community transmission occurs, then health care infrastructure and capacity issues will likely create problems within the overall health care infrastructure, which may also lead to new problems in the current system of organ donations and transplant.3-7 More studies are required to understand the origin, epidemiology, duration of human transmission, and clinical spectrum of COVID-19.8-13
If there is a deceased donor during this pandemic, then there are a some important questions to consider with regard to the established organ donation and transplant system: (1) Will it be ethical to go forward with the current donation and transplant process, which will benefit a few people in need of acute individual treatment (ie, patients in need of organ transplant) but potentially deflect resources from a much larger group of people who are generally exposed to an untenable environment (ie, those people at risk of COVID-19 infection)? (2) Will there be sufficient supply of personal protective equipment (PPE) available to all staff members working in the current donation and transplant program to address the risk of COVID-19 infection? The National Organ and Tissue Transplant Organisation, India has rightly ordered cessation of living-donation transplant procedures and deceased donation program. (3) If we do indulge in this latter form of donation, then we should consider restricting the process to the following groups, with highest need of a transplant: patients who are highly sensitized kidney recipients and/or patients on dialysis with lack of vascular access, patients with acute fulminant liver failure, and high-risk status patients requiring a heart transplant. Additionally, we should consider restricting transplant activities to few well-equipped hospitals in a given city. The COVID-19 pandemic is a unique situation, without precedent of this magnitude in the medical history; therefore, there is no experience or guidelines to tackle this kind of situation in a developing country that has paucity of resources.
The World Health Organization’s (WHO) aggressive pathway of isolate, test, treat, and trace contacts is difficult to implement in a limited-resource setting.1,2 These are key measures to prevent the spread of COVID-19 to stage 3 (community spread). In this article, we will discuss the general prevention aspects of those guidelines, and we will provide our viewpoints in the specific situation of organ transplant.
Nation Lockdown, Social Isolation, Social Distancing, and Prevention of
Nonessential Contacts and Travel
Many developing and developed countries (India, China, Iran, Spain, Italy, and United Kingdom) have imposed a nationwide lockdown after the advisory of social distancing and the prevention of nonessential contacts and travel in an attempt to slow the spread of COVID-19. India observed a self-imposed “Janata curfew” on March 22 from 7 AM to 9 PM at the appeal of the Indian Prime Minister. The nationwide lockdown was subsequently imposed from March 25 to May 3, 2020, in an attempt to slow the spread of COVID-19 in India. This was thought to be the most effective strategy to curb the spread of the virus in a vast country such as India, with a large population and a limited health care system.
Advisory on Organ Transplant
Deceased-donor and living-donor organ transplant programs
Most transplant clinicians and government advisories suggest that elective living-donor transplant programs should be temporarily suspended during the COVID-19 pandemic.1-9
With regard to the current COVID-19 pandemic, the general consensus suggests that the following individuals, who would otherwise be considered potential deceased donors, should not be accepted as deceased donors8-12: (1) individuals who have been exposed to a confirmed or suspected COVID-19-positive patient within the last 14 days; (2) individuals who have returned to India from nations with a high prevalence of COVID-19 within the last 14 days; and (3) individuals whose cause of death was diagnosed as unexplained respiratory failure.
However, support for deceased-donor organ transplant (DDOT) is maintained for the following circumstances: lifesaving transplants, organ shortage, and patients for whom the delay in transplant may lead to morbidity and mortality, including COVID-19 exposure during dialysis. These conditional limi-tations may provide that the only indication for DDOT would be highly sensitized candidates, kidney transplant candidates with lack of vascular access, liver transplant candidates with acute fulminant liver failure, or life-saving heart transplant candidates.
Our collective experience shows that the important points to consider regarding DDOT, for countries with a significantly small percentage of gross domestic product allocated for health care, are availability of the following crucial elements: adequate PPE (eg, N95 masks, gloves, gowns, goggles, face/eye protection); testing kits (there is a currently a global shortage of COVID-19 testing kits); negative-pressure isolation rooms; intensive care unit (ICU) beds; ventilator support; telehealth or telemedicine; trained health care workers (HCW); and hospital beds. Additionally, and of equal importance to this aforementioned list, we must consider the following factors: dynamic nature of this pandemic, variable levels of willingness among potential recipients and/or medical staff; educational updates, and the potential burden on an existing, but fragile, health care system.14-16 We believe that the national and global health care system should prioritize resource allocation toward resolving the COVID-19 pandemic (large population), while deprioritizing resources for DDOT programs (fewer patients), with respect to our resource-limited setting and the fact that cases are rising rapidly worldwide. That is, the benefit to the few must be balanced with the needs of the many. Health care workers should participate in ongoing education and updates regarding COVID-19 for the large population, and ICU beds should be reserved for the near future as required. In this scenario, the ethical principle against doing DDOT is “first, do no harm.” COVID-19 has created a situation with many new and challenging logistical issues that present ethical and financial obstacles to the established programs for DDOT.
Risk of asymptomatic infections and transmission
The prevalence of truly asymptomatic COVID-19 infections in potential donors, recipients, and HCW is unclear, in absence of mass testing. We should attempt to limit the person-to-person transmission of this novel coronavirus from asymptomatic potential carriers who might be in the incubation period, especially hospitals and family settings.17-23 In the absence of mass testing, there is concern with regard to potential asymptomatic transmission of COVID-19 in the setting of HCW interaction with donors and recipients.
For example, in a pilot survey from the Institute of Kidney Diseases and Research Center and Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, India, most patients on dialysis waiting for DDOT for many months expressed that they would rather wait than risk of potential exposure to COVID-19 during the transplant procedure. These patients were less willing to expose their family members to COVID-19 and requested to be called for potential DDOT only after the pandemic situation became under control. Currently, the shortage of HCW is widespread, as reported by many countries, including Italy. Surgeons, too, do not wish to operate under the conditions created by the current pandemic; surgeons on the front lines are at great risk, as the shortage of PPE increases the risk of the most severe form of COVID-19 (in more severe cases, COVID-19 infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death).
Hospital transplant units, equipment, and staff
Access to transplant units
Transplants must be conducted in hospitals, and hospitals treat patients with COVID-19 infection; hence, there may be no COVID-19-free pathway for a transplant unit.
Specialized medical staff
Hospitals do not have dedicated HCW, including transplant infectious disease physicians and availability of psychiatrists to help improve outcomes in COVID-19 transplant patients.
Availability of WHO-standard and WHO-approved personal protective equipment
Adequate PPE resources may not be available in all transplant units; PPE stock is limited and in short supply.
Screening for COVID-19
Resources for COVID-19 screening in both recipients and the potential deceased donor may not be available in all transplant units.
Lack of negative-pressure isolation rooms may lead to spread of virus, especially in cases in which the diagnosis is delayed or missed in recipients.
Limited number of health care workers
The crisis in availability of HCW is common even in normal circumstances, and during the COVID-19 pandemic this problem has been exacerbated. Deceased-donor allocation is performed in some states from public sector hospitals, where approximately 20% of medical HCW are assisting asymptomatic stable patients for essential drug supply; 20% of HCW are devoted to patients with respiratory symptoms; 20% of the HCW are elderly (ie, at high risk) and work from home to reduce risk of exposure; 20% of HCW are suspected or confirmed as positive for COVID-19; and 20% of HCW are working in online education, telemedicine, and telehealth programs.
Inadequate staffing during the COVID-19 pandemic could be magnified by self-isolation of HCW, with the possibility of becoming infected or becoming carriers. Currently, many hospitals are facing severe resource deficits. In addition, the mixing of staff increases the risk of transmission. We should be prepared to face the stage 3 (community transmission) COVID-19 situation and keep a few staff members available for it.
India has a limited number of ICU beds, and the government is converting private hospitals, hostels, and railway coaches to COVID-19 hospitals in preparation for possible increases in the number of cases.
India has a large population. Medical and paramedical HCW should be used for online health education of the general population and patients infected with COVID-19; otherwise, simple home quarantine can become a social stigma in society, and people may attempt to run away or may even attempt suicide.
All organ donation team members and transplant coordinators may need to be diverted as a way to supplement the current pool of HCW who are members of COVID-19 teams.
There are potential restrictions on patients’ access to funds, insurance clearance approvals, grants for transplants, and a variety of other resources.
Presentation and diagnosis
Presentation for COVID-19 infection can be atypical, such as the absence of fever in the transplant population as a result of the immunosuppressed state and associated comorbid conditions such as diabetes, which have been reported by Chinese and Italian sources.8-13,24-27 These presentations may lead to a delayed or missed diagnosis.
With regard to diagnostic testing, potential deceased donors may have fever, cough, dyspnea, respiratory infections, exposure to multiple HCW, and risk-prone travel history, and this information may be unavailable or voluntarily withheld. Without COVID-19 testing, a DDOT should not be performed.
The stock components for COVID-19 testing kits may be limited, and the turnaround time of testing may be lengthy. Both of these factors may increase cold ischemia time, resulting in a delayed graft function and extended ICU stay. One negative COVID-19 test in potential deceased donors does not rule out COVID-19 in the presence of supporting clinical and epidemiologic surveys. The chance of a false-negative test ranges from 2% to 20% and may be caused by poor quality of sample collection, early or late disease, or laboratory or reagent error. There is more concern about the quality and method of sample collection, as the HCW assigned to collect swabs for COVID-19 testing may not have proper training associated with the anxiety of transmission in a less than ideal setting. Pharyngeal and nasal swabs may not have adequate sensitivity for COVID-19. While certainly not definitive, this study raises concerns about “ruling out” COVID-19 on the basis of combined pharyngeal and nasal swabs obtained at a single time point.28 It is difficult to rule out the possibility of transmission from at least some deceased organ donors infected with COVID-19. A blood sample should always be preserved if proceeding with any such donation for future reference and testing.
Management of COVID-19 in transplant patients
A few centers have tried antivirals, hydroxychloroquine (HCQ), and macrolides in COVID-19 patients with limited and variable results.1 There are limited data on efficacy of lopinavir/ritonavir along with the drug interaction of ritonavir with cyclosporine, tacrolimus, and sirolimus. Hydroxychloroquine and azithromycin cannot be used in heart transplant patients nor in patients with QT prolongation (as revealed by electrocardiography). As of April 19, 2020, there is no treatment approved by the Central Drugs Standard Control Organisation (India) or Food and Drug Administration (USA) for COVID-19 in transplant patients.
Safeguards for health care workers, organ procurement organizations, and
recovery surgeons, as well as risk of transmission
The health and safety of all the HCW in the transplant program are of paramount importance. A number of procurement and transplant staff have raised concerns regarding their personal risk of contracting COVID-19 during surgery, especially considering the current absence of vaccine, absence of established efficacious therapy, and absence of definitive effective prophylaxis. The pressure on the health care system is very high in several countries, and increasing numbers of HCW infected with COVID-19 are being reported. Hence, increasing the risk to HCW by proceeding with a nonurgent DDOT (ie, DDOT that could be delayed until a later date with greater safety to the recipient) is perhaps unwarranted. In the event of COVID-19 transmission, many HCW will then require isolation and/or quarantine, increasing the burden on the health care system and resulting in a temporary absence of trained HCW.
The National Task Force for COVID-19, recently established by the Indian Council of Medical Research, has issued a recommendation for empirical use of HCQ for prophylaxis against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) for high-risk populations, such as asymptomatic HCW involved in the care of suspected or confirmed cases of people infected with COVID-19, as well as asymptomatic household contacts of people with laboratory-confirmed diagnosis of COVID-19. This protocol recommended by the Indian Council of Medical Research National Task Force for COVID-19 was approved by the Drugs Controller General of India.1 The placement of HCW under prophylaxis should not instill a sense of false security. There is a risk of shortage of HCQ if there is overuse of HCQ for prophylaxis of SARS-CoV-2 infection for high-risk populations; also, there is risk of misuse by HCW who may self-medicate with HCQ in response to anxiety/fear of infection. Hydroxychloroquine in high doses is known to be toxic.29
Elderly people and people with diabetes may be at greater risk for mortality than the general population. The expanded-criteria deceased kidney donor or an uncontrolled donation after cardiac death donor could represent a greater risk of delayed graft function in recipients, as well as longer stays in the ICU and a potential risk of developing COVID-19 infection by exposure to HCW. Cases of uncontrolled donation after cardiac death should be canceled because of the complex logistics and the difficulty of timely screening.
Many centers are presently struggling to care for existing patients on dialysis and transplant recipients during this COVID-19 pandemic. Hence, all workups of both donors and recipients (eg, imaging, functional evaluation) for living-related organ transplant programs and DDOT programs have been postponed.
Ethically, there should be no harm in diverting resources (eg, the large group of people involved in deceased-donation transplants) away from potential recipients with end-stage organ failure, especially in cases of kidney disease, for which dialysis is a safe and available alternative. The benefit to one patient versus risk to many should be evaluated in the context of the prevalence of COVID-19 and an effective health care system. Anxiety and distress related to concerns of COVID-19 exposure could lead to adverse outcomes in recipients, if transplants were to proceed at the same pace as in the era before the COVID-19 pandemic; these suboptimal transplant outcomes may lead to regulatory review. Organ allocation per wait list would be difficult to maintain because potential recipients may encounter impediments to road, rail, or air travel that could result in untimely arrival at the transplant hospital. Health care workers could become concerned if posttransplant recipients were to develop fever, cough, dyspnea, and unexplained chest infection, especially while awaiting COVID-19 test reports (or if test kits are not available). COVID-19 source confirmation (whether from donor or HCW or because of the recipient’s travel history) would be difficult when COVID-19 is confirmed after transplant.
Family Support Constraints at the Time of Transplant
After transplant, recipients may not have access to family members’ support because of travel restrictions. Even if family members are available for support, there may be logistical challenges. Patients, family members, and even doctors have had issues in obtaining temporary lodging near the hospital because of fears regarding increased exposure to COVID-19.
Posttransplant Follow-Up Issues
It is not known when COVID-19 is likely to be eradicated or controlled. Transplant units are advised to consider ways to limit hospital attendance for patients by rescheduling nonurgent outpatient appointments. Access to maintenance immunosuppression drugs and support from family members, as well as frequent hospital visits, after transplant may be difficult and could lead to noncompliance and suboptimal outcomes. There are limited data about levels of immunosuppression in suspected or confirmed COVID-19 cases, but generalized immunosuppression reduction may jeopardize organ function. As mentioned, travel restrictions may be an impediment for transplant patients because of the current high incidence of COVID-19 cases. The benefit of wearing masks in public is advocated, although not necessarily backed by data; this topic is controversial even for transplant patients, as the effectiveness of masks to prevent COVID-19 infection has not been firmly established.9 The current 2.3% mortality rate of COVID-19 infection among the general population will likely be higher among transplant recipients.30 A summary of these reasons to place higher priority on the COVID-19 pandemic (versus DDOT) in developing countries is shown in Table 1.
We should be prepared for potential increasing severity of the COVID-19 pandemic; however, more data are required to support the notion that all HCW, donors, and recipients in a transplant center should be screened for COVID-19. Some important questions remain, which we list here: Should candidates for organ transplant sign an additional consent form to acknowledge and accept the increased risk of developing COVID-19 infection? Does immunosuppression prolong viral clearance shedding and risk of transmission to others?22 What should be the immunosuppression protocol during the COVID-19 pandemic? Can there be transmission of COVID-19 from donor to recipient and systemic manifestation after transplant? Is convalescent plasma useful to treat COVID-19?31
All transplant units must be aware of national and local guidelines for managing patients with COVID-19. We believe that the national and global health care system should assign high priority to the needs of people affected by the COVID-19 pandemic (large population), while lower priority should be assigned to nonurgent DDOT (relatively few patients) in a resource-limited setting. Transplant units should consider a case-by-case evaluation when assessing the convenience of carrying out lifesaving deceased-donor kidney transplant in a resource-limited settings. The ethics regarding the appropriate balance of priorities, ie, the benefits to the few versus the risk to the many, should be given serious consideration before proceeding with any DDOT case. The approval of DDOT during the COVID-19 pandemic should be limited to the following few situations: highly sensitized candidates or candidates with a lack of vascular access (in kidney transplant), acute fulminant liver failure in candidates for liver transplant, or life-saving heart transplant candidates. In addition, if cases are deemed worthy to proceed, then these cases should be restricted to centers that are fully staffed and fully equipped with PPE, along with separate areas for isolation, availability of diagnostic kits, and presence of surgeons who are willing to take the risk.
DOI : 10.6002/ect.2020.0134
From the 1Department of Nephrology and Transplantation, Smt. G. R. Doshi and
Smt. K. M. Mehta Institute of Kidney Diseases and Research Center and Dr. H. L.
Trivedi Institute of Transplantation Sciences, Ahmedabad, India; the 2Indian
Society of Organ Transplantation; the 3National Organ and Tissue Transplant
Organization, New Delhi, India; the 4Department of Surgery, Vardhman Mahavir
Medical College and Safdarjung Hospital, New Delhi, India; the 5Multi Organ
Harvesting Aid Network Foundation and the 6Transplant Authority of Tamil Nadu,
Chennai, India; the 7Department of Nephrology, Sanjay Gandhi Postgraduate
Institute of Medical Sciences, Lucknow, India; the 8Department of
Transplantation Surgery, Indraprastha Apollo Hospitals, New Delhi, India; the
9Department of Nephrology, Indian Institute of Technology (Banaras Hindu
University), Varanasi, India; the 10Department of Nephrology and
Transplantation, Osmania Medical College, Hyderabad, India; the 11Gujarat State
Organ and Tissue Transplant Organization, Ahmedabad, India; the 12Division of
Nephrology, Multi-Organ Transplant Program, Department of Medicine, McGill
University Health Centre, Montreal, Quebec, Canada; and the 13Department of
General Surgery Division of Transplantation, Başkent University, Ankara, Turkey
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no potential declarations of interest. All transplant units must be aware of national and local guidance for managing patients with COVID-19. The authors thank Dr. Andrea Herrera-Gayol for critical review of the manuscript.
Corresponding author: Vivek Kute, Department of Nephrology and Transplantation, Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, India
Phone: +91 9099927543
Table 1. Reasons for COVID-19 Pandemic Control to Take Priority Over Deceased-Donor Organ Transplants in Developing Countries1-6