Utilization of deceased donors during a pandemic: argument against using SARS‐CoV‐2–positive donors

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained health care resources, and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplant continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of coronavirus disease 2019 (COVID‐19)–positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID‐19–positive donors. The factors we consider include (1) the risk of blood transmission of SARS‐CoV‐2, (2) involvement of donor organs, (3) lack of effective therapies, (4) exposure of health care and recovery teams, (5) disease transmission and propagation, and (6) hospital resource utilization. While we acknowledge that transplant fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients but also to the community and to health care workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID‐19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplant societies.     

Early impact of COVID‐19 on transplant center practices and policies in the United States

COVID‐19 is a novel, rapidly changing pandemic: consequently, evidence‐based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center‐level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID‐19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID‐19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID‐19. Shortage of COVID‐19 tests was reported by 42.5%. Respondents reported a total of 148 COVID‐19 recipients from <1 to >10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center‐level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence‐based practices.     

Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients

Over 1 000 000 cases of coronavirus disease 2019 (COVID‐19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID‐19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus–related hepatocellular carcinoma and was confirmed to have COVID‐19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low‐dose methylprednisolone‐based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living‐related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID‐19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID‐19. These effectively treated cases can provide a basis for immunosuppressant management of COVID‐19‐positive SOT recipients.     

Fatal outcome in a liver transplant recipient with COVID‐19

Liver injury is common in patients with COVID‐19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID‐19 in a patient who underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID‐19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.     

Two distinct cases with COVID‐19 in kidney transplant recipients

The fatality of novel coronavirus disease 2019 (COVID‐19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID‐19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36‐year‐old man who underwent KT 3 years ago. He was diagnosed with COVID‐19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID‐19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug‐to‐drug interaction. The second case was developed in a 56‐year‐old man without any symptoms. He received a second KT from an ABO‐incompatible donor 8 years ago. He was diagnosed with COVID‐19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.     

COVID‐19 in a high‐risk dual heart and kidney transplant recipient

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly infecting people worldwide, resulting in the infectious disease coronavirus disease 19 (COVID‐19) that has been declared a pandemic. Much remains unknown about COVID‐19, including its effects on solid organ transplant (SOT) recipients. Given their immunosuppressed state, SOT recipients are presumed to be at high risk of complications with viral infections such as SARS‐CoV‐2. Limited case reports in single SOT recipients, however, have not suggested a particularly severe course in this population. In this report, we present a dual‐organ (heart/kidney) transplant recipient who was found to have COVID‐19 and, despite the presence of a number of risk factors for poor outcomes, had a relatively mild clinical course.     

Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report

Initial experience with lung transplant of COVID-19–positive donors was marked by disappointing results, including a reported case of mortality through donor to recipient transmission of infection. However, since that time a number of improvements in preventative and therapeutic measures against COVID-19 have been developed. We present the case of a 51-year-old woman with scleroderma-associated interstitial lung disease who was awaiting lung transplant. A potential donor with excellent lung physiology was located; however, initial testing on bronchoalveolar lavage (BAL) was positive for COVID-19. The donor had tested positive 2 weeks prior and had symptomatically recovered. Our patient had been fully vaccinated but not seroconverted. Given the history of a donor with recovering COVID infection and a fully immunized recipient, our multidisciplinary team elected to proceed with the transplant. The patient successfully underwent bilateral lung transplant with standard induction immunosuppression. Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19. Serial bronchoalveolar lavages post transplant have been negative for COVID-19. The patient has done well after transplant. She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.     

Successful treatment of severe COVID‐19 pneumonia in a liver transplant recipient

Coronavirus disease 2019 (COVID‐19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID‐19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50‐year‐old male post liver transplantation who contracted COVID‐19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low‐dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID‐19 pneumonia.     

COVID‐19 pneumonia in a kidney transplant recipient successfully treated with tocilizumab and hydroxychloroquine

Coronavirus disease 2019 (COVID‐19) pneumonia has been poorly reported in solid organ transplanted patients; prognosis is uncertain and best management unclear. We describe the case of a 61‐year‐old kidney transplant recipient with several comorbidities who was hospitalized and later received a diagnosis of COVID‐19 pneumonia; the infection was successfully managed with the use of hydroxychloroquine and a single administration of tocilizumab, after immunosuppression reduction; the patient did not require mechanical ventilation. During the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, transplant clinicians should be readily informed about new cases of COVID‐19 pneumonia in solid organ transplant recipients, with focus on therapeutic strategies employed and their outcome.     

SARS‐CoV‐2 infection in two patients following recent lung transplantation

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) that causes coronavirus disease 2019 (COVID‐19) has become a global health problem with pandemic character. Lung transplant recipients may be particularly at risk due to the high degree of immunosuppression and the lung being the organ primarily affected by COVID‐19. We describe a 16‐year‐old male and a 64‐year‐old female recently lung transplanted patients with COVID‐19 during inpatient rehabilitation. Both patients were receiving triple immunosuppressive therapy and had no signs of allograft dysfunction. Both patients had close contact with a person who developed COVID‐19 and were tested positive for SARS‐CoV‐2. Subsequently, both patients underwent systematic screening and SARS‐CoV‐2 was ultimately detected. Although the 16‐year‐old boy was completely asymptomatic, the 64‐year‐old woman developed only mild COVID‐19. Immunosuppressive therapy was unchanged and no experimental treatment was initiated. No signs of graft involvement or dysfunction were noticed. In conclusion, our report of patients with asymptomatic SARS‐CoV‐2 infection and mild COVID‐19, respectively, may indicate that lung transplant recipients are not per se at risk for severe COVID‐19. Further observations and controlled trials are urgently needed to study SARS‐CoV‐2 infection in lung transplant recipients.     

Severe COVID‐19 in a renal transplant recipient: A focus on pharmacokinetics

The current coronavirus disease 2019 (COVID‐19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35‐year‐old renal transplant recipient who suffered from a severe COVID‐19 pneumonia. The clinical course was complicated by extreme overexposure to the mammalian target of rapamycin inhibitor everolimus, following coadministration of chloroquine and lopinavir/ritonavir therapy. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence‐based COVID‐19 therapy and concurrent pressure for exploration of experimental pharmacological treatment options. However, the risk‐benefit balance of experimental or off‐label therapy may be weighed differently in organ transplant recipients than in otherwise healthy COVID‐19 patients, owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy. With this case report, we aimed to achieve increased awareness and improved management of drug‐drug interactions associated with the various treatment options for COVID‐19 in renal transplant patients.     

Clinical course of COVID‐19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report

The novel coronavirus disease 2019 (COVID‐19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID‐19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID‐19 pneumonia, and despite completing a 5‐day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off‐label, single‐dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID‐19. Future investigation of the effects of immunomodulators among transplant recipients with COVID‐19 infection will be important.     

Salivary detection of SARS‐CoV‐2 (COVID‐19) and implications for oral health‐care providers

The coronavirus disease 2019 (COVID‐19) pandemic has become a major public health crisis. The diagnostic and containment efforts for the disease have presented significant challenges for the global health‐care community. In this brief report, we provide perspective on the potential use of salivary specimens for detection and serial monitoring of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), based on current literature. Oral health‐care providers are at an elevated risk of exposure to COVID‐19 due to their proximity to nasopharynx of patients, and the practice involving the use of aerosol‐generating equipment. Here, we summarize the general guidelines for oral health‐care specialists for prevention of nosocomial transmission of COVID‐19, and provide specific recommendations for clinical care management.     

Renal transplantation during the SARS‐CoV‐2 pandemic in the UK: Experience from a large‐volume center

There is uncertainty about the safety of kidney transplantation during the SARS‐CoV‐2 pandemic due to the risk of donor transmission, nosocomial infection and immunosuppression use. We describe organ donation and transplant practice in the UK and assess whether kidney transplantation conferred a substantial risk of harm. Data from the UK transplant registry were used to describe kidney donation and transplant activity in the UK, and a detailed analysis of short‐term, single‐center, patient results in two periods: during the pre‐pandemic era from 30th December 2019 to 8th March 2020 (“Pre‐COVID era”) and the 9th March 2020 to 19th May 2020 (“COVID era”). Donor and recipient numbers fell by more than half in the COVID compared to the pre‐COVID era in the UK, but there were more kidney transplants performed in our center (42 vs. 29 COVID vs. pre‐COVID respectively). Overall outcomes, including re‐operation, delayed graft function, primary non‐function, acute rejection, length of stay and graft survival were similar between COVID and pre‐COVID era. 6/71 patients became infected with SARS‐CoV‐2 but all were discharged without critical care requirement. Transplant outcomes have remained similar within the COVID period and no serious sequelae of SARS‐CoV‐2 infection were observed in the peri‐transplant period.     

Early experience of COVID‐19 in 2 heart transplant recipients: Case reports and review of treatment options

The coronavirus disease 2019 (COVID‐19) pandemic poses special challenges to immunocompromised transplant patients. Given the paucity of proven data in treating COVID‐19, management of these patients is difficult, rapidly evolving, and mainly based on anecdotal experience. We report 2 cases of heart transplant (HT) recipients with COVID‐19. The first is a 59‐year‐old female with HT in 2012 who presented on March 20, 2020 with fever, hypoxia, and ground‐glass opacities on chest X‐ray. She quickly progressed to acute hypoxic respiratory failure and vasoplegic shock. Despite reduction in immunosuppression and treatment with tocilizumab, intravenous immunoglobulin, hydroxychloroquine, lopinavir/ritonavir, and broad‐spectrum antibiotics, she ultimately died from multiorgan failure. The second case is a 75‐year‐old man with HT in 2000 who presented on April 2, 2020 after curbside testing revealed positive COVID‐19. Given a milder presentation compared to the first patient, antimetabolite was discontinued and only hydroxychloroquine was started. Because of a lack of clinical improvement several days later, tocilizumab, methylprednisolone, and therapeutic anticoagulation were initiated. The patient clinically improved with decreasing oxygen requirements and was discharged home. These 2 cases highlight the wide range of different presentations of COVID‐19 in HT recipients and the rapidity with which the management of these patients is evolving.     

The impact of the COVID‐19 outbreak on liver transplantation programs in Northern Italy

In January 2020, Novel Coronavirus Disease 2019 (COVID‐19) resulted in a global pandemic, creating uncertainty toward the management of liver transplantation (LT) programs. Lombardy has been the most affected region in Italy: the current mortality rate of COVID‐19 patients is 18.3% (10 022 deaths; April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18‐74) whereas mean recipient age was 55 (13‐69); mean MELD score was 12 (6‐24). All donors underwent screening for SARS‐CoV‐2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. Sixteen patients are alive after an average of 30 days post‐LT (range 3‐46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop LT programs. Several key lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement.     

Liver Transplantation Using Chagas‐Infected Donors in Uninfected Recipients: A Single‐Center Experience Without Prophylactic Therapy

Organ shortage is the first cause of death on liver transplant waiting lists. As a consequence, we recently decided to expand liver acceptance to those organs that could potentially transmit infectious diseases to their recipients. On January 2010, we initiated a prospective protocol using livers from Chagas‐infected donors for transplanting uninfected recipients without using prophylactic therapy. During a 13‐month period, 9 of 37 (24%) liver transplants were performed within this protocol. After transplant, each recipient was sequentially and strictly monitored for infection transmission using the Strout method and promptly treated with benznidazole if this occurs. During follow‐up, two patients died without Chagas infection and only two (donor‐derived T. cruzi transmission rate: 2/9; 22%) patients developed donor‐derived Chagas transmission without clinical symptoms. The median follow‐up time of the seven live patients was 15 months (range: 13–20). At present, all are symptoms‐free with excellent allograft function and without evidence of Chagas disease. In conclusion, we consider that Chagas‐infected donors are a promising source of liver grafts that could reduce the growing mortality on liver waiting lists in America. Relevant data from larger prospective studies are required to confirm these preliminary excellent results.     

Case report of COVID‐19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?

COVID‐19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Immunocompromised patients often present atypical presentations of viral diseases. Herein we report a case of a COVID‐19 infection in a solid organ transplant recipient, in which the first clinical symptoms were of gastrointestinal viral disease and fever, which further progressed to respiratory symptoms in 48 hours. In these high risk populations, protocols for screening for SARS‐Cov2 may be needed to be re‐evaluated.