EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Respiratory viral infections are common in transplant recipients as a result of long-term immunosuppression and comorbidities.^1,2 Notably, transplant patients have comorbidities that predispose those with the novel coronavirus disease (COVID-19), the disease caused by the SARS-CoV-2 virus, to severe disease.^3,4 Transplant recipients with COVID-19 disease have high rates of hospitalization, intensive care unit admission, and adverse events.^4,5

Emerging reports have investigated the effects of COVID-19 in liver transplantation, but the data are still scarce. De Barros Machado and Ianhez⁶ reported a COVID-19 case in a 69-year-old man with sequential liver-kidney transplant under triple immunosuppression (tacrolimus, mycophenolate, and prednisone) and recent hospital discharge after laparoscopic appendectomy. The patient presented with low-grade fever and pneumonia findings on chest computed tomography, and the immunosuppression regimen was modified (decreased tacrolimus, mycophenolate cessation, and increased prednisone) with good outcomes (discharged at 12 days).6 Atypical presentation has also been reported in a 50-year-old male liver transplant recipient, manifesting with symptoms similar to influenza pneumonia; this case reported that immunosuppression withdrawal and systemic low-dose steroids resulted in resolution of symptoms.⁷ In a recent report by Hong and associates,⁸ a 57-year-old woman received a liver graft from her 28-year-old daughter who had unknown COVID-19 status at liver transplant and was later (day 3 after donation) confirmed to be COVID-19 positive. The recipient was initially treated with prophylactic lopinavir/ritonavir and was then switched to hydroxychloroquine (due to drug interaction between tacrolimus and antivirals) and remained SARS-CoV-2 negative at 2 months posttransplant. A high clinical suspicion is required, as the risk of misdiagnosis is high as a result of false negative tests.⁹ In the current issue of Transplant Infectious Disease and in contrast to previous reports, Gao and associates¹⁰ reported 3 cases of liver transplant with initially mild disease that progressed to severe COVID-19 (fever > 39 °C), with 1 patient who was infected during the perioperative period. The role of immunosuppression and the disease course in liver transplant recipients remain to be elucidated.

Liver Transplant Recommendations in the Era of COVID-19
In general, liver disease societies recommend the use of telehealth approaches (100%), continued immunosuppressive therapy (93%), cessation of nonurgent visits (86%), and minimization of consultations and limited number of people accompanying the patient (57%).¹¹ Strict measures should be applied to ensure prevention of transmission, as in the case of first organ donation in a 68-year-old female recipient after the reopening of Wuhan, China. In this case, a comatose 61-year-old male donor was quarantined and meticulously investigated (history investigation through contact with the family, repeated SARS-CoV-2 polymerase chain reaction in oropharyngeal swab specimens, antibody tests); in the report, the authors suggested an interval of more than 7 days between donor admission and donation.¹²

The American Society of Transplantation (AST) suggests that all nonurgent transplant procedures should be suspended and that organ donors who may have been exposed (high-risk areas, close contacts with suspected/confirmed COVID-19) should not be considered for donation for an interval of 2 to 4 weeks.^13,14 In addition, the Transplant Infectious Disease Section of the Transplantation Society recommends against the procurement of organs from donors with unspecified respiratory failure.¹⁵ The detrimental effects of COVID-19 on deceased donor liver transplant availability (11% decrease) and on the number of adult deceased donor liver transplant procedures (24.7%) have been demonstrated by Agopian and colleagues16 who analyzed data from the OPTN/UNOS database. Similarly, in the Netherlands, the number of transplant procedures in children with end-stage organ failure has significantly decreased, with a concomitant decrease in organ donations among all organ transplant services.¹⁷

This situation gives rise to ethical dilemmas, where the benefits of a life-saving nonurgent procedure must be balanced against the risk of COVID-19 transmission to the patient and the community. Both health care workers and patients must adhere to the proposed safety measures to prevent transmission and to ensure that transplant programs can continue to operate, without placing the patients or the community at risk. However, transplant organizations must frequently update their recommendations to counteract the detrimental effects of the pandemic on the transplantation community.

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