EXPERIMENTAL AND CLINICAL TRANSPLANTATION

The recent COVID-19 outbreak has quickly become a worldwide pandemic emergency. The course of this pandemic is still unknown, with more than 6 million cases identified and over 370 000 deaths globally as of June 1, 2020. The uncertainty and anxiety during this period will have a detrimental effect on the global health system. The organ transplantation field has been negatively affected by the COVID-19 pandemic, especially in regions where the intensity of cases exceeds the available capacity of the health care resources. Recently, scattered data have been published in the English literature, mainly in case reports and letters to the editor, that describe the effect of COVID-19 on donors and recipients of abdominal solid organs. Our objective is to review and draw conclusions from these data.

Key words : Coronavirus disease, Organ donor, Recipient management

An outbreak of the novel coronavirus disease (COVID-19) started in late December 2019 in Wuhan, China, and quickly became a worldwide pandemic emergency.^1-4 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, which is highly contagious and may rapidly progress to acute respiratory distress syndrome with potential multiorgan failure and death.^5,6 Over the past few decades, transplant has become an established treatment for end-stage organ diseases. Although the number of patients who receive transplants is steadily increasing, infectious diseases still pose a major obstacle to the success of organ transplants and the ongoing posttransplant care of recipients. The use of immunosuppressive medications increases the risk of severe infections caused by viral outbreaks, such as SARS-related coronavirus simian, pandemic influenza A virus (H1N1), HIV, and others. For each of these threats, transplant programs around the world cooperated to assess risk and generate treatment algorithms for donors, recipients, and health care workers; this collaboration has facilitated the ongoing success of this lifesaving therapy in a safe and effective manner.^7-11

Currently, we are facing a COVID-19 pandemic, with millions of people who have tested positive for the virus, as well as hundreds of thousands of deaths worldwide; in addition, there may be many more cases that are undiagnosed. The organ transplantation field has been negatively affected by the COVID-19 pandemic, especially in regions where the intensity of cases exceeds the available capacity of the health care resources. Recently, scattered data have been published in the English literature, mainly in case reports and letters to editors, that describe the effect of COVID-19 on donors and recipients of abdominal solid organs. Our objective is to review and draw conclusions from these data.

Donor Case Management
The SARS-CoV-2 virus is primarily isolated from the respiratory tract. However, in about 15% of cases, this virus was isolated from the blood. Therefore, all organs may transmit the virus if the organs are from a donor infected with the virus.¹²

Because the exact penetration of COVID-19 in the worldwide community is unknown, donor screening from both a clinical and laboratory perspective should be mandatory. The most effective method to screen donors is by incorporating epidemiological, clinical, and laboratory parameters. The nucleic acid test (NAT) for SARS-CoV-2 is considered the cornerstone for screening donors. Specimens can be collected by nasopharyngeal swab or bronchoalveolar lavage. However, there are limitations to these methods; the nasopharyngeal swab has a high rate of false-negative results caused by inappropriate collections, and bronchoalveolar lavage is problematic because of the need for bronchoscopy and the potential risk of aerosolization.

Availability of laboratories and rapid NAT kits are essential for organ procurement organizations to treat and follow patients and clear them for organ donation; patients who test positive are not qualified for donation.

Kumar and colleagues summarized their methods for donor and recipient screening from multiple countries, including Canada, Switzerland, Spain, Italy, Korea, and Japan. They concluded that deceased and living donors should be screened with NAT.¹² The current recommendations from the American Society of Transplant Surgeons (ASTS) mandate clinical and NAT screening for both deceased and living donors.¹³

Transplant Process and Recipient Case Management
In addition to the risk of exposure of recipients to organs with false-negative COVID-19 results, the decision to transplant should proceed only after careful consideration of the following items: the institutional capacity to provide pre-, peri-, and postoperative care, including availability of beds, blood component supply, and outpatient support; the risk of inducing immunosuppression in the organ recipient and jeopardizing survival in the midst of a pandemic; and the risk-to-benefit ratio of postponing versus proceeding with the transplant.

Recently, more patients in different countries have been admitted to hospitals because of severe COVID-19 infections. As the pandemic progresses, there may be shortages of inpatient beds, intensive care services, and blood products. In those circumstances, and before the decision to proceed with a transplant, it is crucial that the transplant team evaluate each organ offer for the specific potential recipient with careful assessment of resource availability and total course. Centers must also have the capacity to quarantine and treat recipients and caregivers in cases of perioperative COVID-19 exposure/infection.

The ASTS13 and Kumar and colleagues¹² recommend that decisions for transplant should be collective and considered on the basis of risk tolerance, hospital capacity, and degree of virus activity in the jurisdiction. If the health care system is capable of fully providing pre-, peri-, and postoperative care for the recipient and the health care personnel, then lifesaving transplants should proceed. With the increased burden on the health care system, small bowel, pancreas, and islet transplant procedures should be suspended as the first priority, followed by living donor kidney transplants and living donor liver transplants for stable recipients.

Deceased donors for highly sensitized kidney patients as well as liver patients with high scores for the Model for End-stage Liver Disease (MELD scores above 25) should be considered on a case-by-case basis following a thorough evaluation of each organ offer for the specific potential recipient. Recipients and families should understand and consent to the risks and benefits during this uncertain time. Eventually, should the health care system become overwhelmed, a 100% reduction in all transplant activities may be unavoidable. After the peak of the pandemic has passed, when the plateau phase is underway, transplant programs should expect an increase in deceased donor urgent cases followed by additional elective living donor cases.

Recipient screening remains controversial. Kumar and colleagues¹² recommend clinical screening for all recipients, reserving NAT for symptomatic patients and for asymptomatic patients within highly infected areas. The ASTS13 recommends NAT for every recipient when feasible.

Modification of hospital activities in response to the increasing number of patients infected with COVID-19 will restrict perioperative care and outpatient follow-up. Urgent visits will have priority, and “telehealth” appointments and telephone calls can be used for routine elective transplant wellness visits.

Human resource management is crucial issue; all hospitals should have protocols in place to prevent transmission, along with clear backup plans. The use of personal protection measures to mitigate the risk of infection during high-risk procedures, such as bronchoscopy in a potential deceased donor, is essential. Donor procurements in high-risk areas should be performed by the local teams, and organ procurement organizations should arrange the shipment of the organs to the destinations. The physical and mental health of the transplant team should be closely monitored, and team members who experience any symptoms compatible with COVID-19 should self-isolate until tested.

Patients on wait lists and recipients should minimize exposure and practice social distancing. They should attempt to acquire a 3-month supply of medication, and they must contact their transplant center if they experience symptoms of COVID-19.

In the current climate, apart from the Centers for Medicare and Medicaid Services’ recommendations to continue lifesaving transplants, the decision for each and every transplant is made locally at each transplant center. The components of this decision tree are largely similar, regardless of the variables. The overarching question to consider is, How is the reallocation of resources away from transplant patients and pushed to COVID-19 patients affecting the center’s capability to perform successful transplants? Additionally, an assessment of the wait list mortality is important. To succeed, a transplant center director must be familiar with the local projections for incidence of COVID-19, their hospital capacity, and local mortality. Figure 1 depicts the complex decision-making process for successful transplants in the midst of this pandemic.

Immunosuppression Effect and the Approach to Recipients Infected with COVID-19
D’Antiga analyzed preliminary data from almost 300 children with immunosuppression, who were from Bergamo in the Lombardy region of Italy, one of the most affected regions in the world with regard to COVID-19. D’Antiga concluded that immunosuppression in these children did not increase the risk of COVID-19 severe pulmonary disease compared with the general population. Children under the age of 12 years had mild symptoms regardless of their immune status. Old age, male sex, and comorbidities (especially obesity) were risk factors for severe disease.¹⁴ These data support a decision to proceed with lifesaving treatments such as transplantation or chemotherapy for cancer in children.

At the time of this writing, several case reports were published in the English literature^15-17 that described the course and management of COVID-19 infection in adults with a history of abdominal organ transplant.

Zhu and colleagues¹⁵ and Guillen and colleagues¹⁶ published 2 case reports about 2 male patients (12 and 4 years old) who had kidney transplants before being diagnosed with COVID-19 infections. The authors concluded that the overall clinical characteristics (symptoms, laboratory examinations, and radiology findings) were similar to those of COVID-19 patients with no transplant. However, immunocompromised patients may present with atypical clinical manifestations. Both patients were admitted for supportive care and isolation. In addition to current treatment trials for COVID-19 infection in immunocompetent patients, the authors recommended reduction or temporary discontinuation of immunosuppressant medications during the acute phase of the infection. They also emphasized the role of corticosteroids in the treatment protocol, as the immunosuppressive effect might protect the renal allograft from acute rejection. Moreover, the anti-inflammatory effect of corticosteroids may reduce alveolar exudation and relieve systemic symptoms caused by the inflammatory reaction.^6,18

Qin and colleagues17 reported their experience with COVID-19 infection in a liver transplant recipient. The diagnosis was confirmed 12 days posttransplant. The patient presented with persistent fever with typical pneumonia changes visible in the chest images. Because of an acute phase after transplant and the risk of rejection, immunosuppressant medications and glucocorticoids were maintained and gradually titrated to a lower dose.

More recently, studies from larger cohorts of patients from experienced centers in Turkey have been published that described the incidence and outcomes of COVID-19 in abdominal solid-organ transplant recipients and patients on hemodialysis. Akdur and colleagues¹⁹ reported on 583 transplant recipients who were largely unaffected by the pandemic, apart from one kidney recipient who presented with the typical signs and symptoms and tested positive for COVID-19. This patient received treatment with hydroxychloroquine for 5 days, and immunosuppressive treatment was discontinued. After 14 days, his COVID-19 polymerase chain reaction test was negative. Immunosuppressive treatment was resumed at previous doses, and COVID-19 treatment was stopped.

Arslan and colleagues20 compared 4 separate patient groups, ie, hemodialysis and normal kidney function patients with and without COVID-19 infection, and found that the incidence of COVID-19 was not greater in the hemodialysis group.

Based on the logical extension of data from other viral infections, Kumar and colleagues¹² recommended avoiding induction therapy or, if induction therapy proceeds, then the use of an interleukin 2 receptor antagonist for induction rather than polyclonal globulin induction may be an important consideration during COVID-19 pandemic. In light of this the paucity of data, the ASTS13 recommends that lymphocyte depletion agents, if used, should be used with great caution.

In conclusion, in addition to the conventional supportive treatments, experimental therapies for COVID-19 should be given to recipients infected with the virus. These therapies include antiviral agents (remdesivir), anti-HIV agents (lopinavir/ritonavir/darunavir-cobicistat), anti-inflammatory agents (interferon beta), antiparasitic agents (hydroxychloroquine), immunoglobulin from recovered COVID-19 patients, reduction of interleukin 6 in critically ill patients with tocilizumab, discontinuation of maintenance immunosuppressants, and blunting the inflammatory response with a trial of corticosteroids,^21,22as well as combinations of these therapies.

The worldwide uncertainty and anxiety caused by the COVID-19 pandemic will have a detrimental effect on the global health care system. The course of this pandemic is still unknown; however, there is a prediction that the peak of the disease may last several months, to be followed by a plateau, and then seasonal circulation of the virus. The transplant community should modify daily surgical, experimental, and research activities. Recent data have shown that the rate of infection and the outcomes in transplant recipients are similar to the general population. However, it is crucial to continue investigating COVID-19 management, outcomes, prognosis, and vaccination in this unique patient population. Teamwork, as well as worldwide shared knowledge and experience, will facilitate progress for transplant programs during this pandemic.

Volume: 20 Issue: 9 September 2022

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