Liver transplantation from a SARS-COV-2-positive donor: A road ahead or not

Abstract

The COVID-19 pandemic has had a remarkable impact on the field of liver transplantation. Increasing evidence demonstrates a minimal risk of transmission of SARS-CoV-2 from non-lung donors who test positive for SARS-CoV-2; however, the risks of donor-derived SARS-CoV-2 from liver donors are unknown. We present our experience with two cases in which a liver was transplanted successfully from a brain-dead donor with incidental SARS-CoV-2 infection. Both donors were asymptomatic SARS-CoV-2-positive with negative bronchoalveolar lavage polymerase chain reaction (BAL PCR) and mechanism of death unrelated to COVID-19. Both the recipients did well after transplant and went home with a well-functioning liver. One patient did get readmitted and was found to be SARS-CoV-2-positive; however, it was probably related to hospital exposure rather than donor-derived. SARS-CoV-2-positive donors in select cases may be used for organ donation and liver transplant is safe for recipients.

Introduction

The COVID 19 pandemic has had a remarkable impact on the field of liver transplantation. At the beginning of the pandemic, several transplant centers were severely impacted and transplant was briefly paused due to various reasons such as overwhelmed hospitals and staff members, bed occupancy, ICU shortages, extracorporeal membrane oxygenation and ventilator occupancy. However, cities with fewer cases, hospital admissions and deaths from COVID-19 still continued to perform liver transplantation. There were several guidelines published by the transplant societies with recommendations based on CDC guidelines [1]. All donors were being tested for SARS-CoV-2 and those testing positive were not initially being considered for donation at the beginning of pandemic. This step was taken for safety of patients, doctors, nurses and all the staff involved in the care of the transplanted patient [2], [3], [4]. There was no evidence at the beginning of pandemic about the risk of donor-to-recipient SARS-CoV-2 transmission. This deeply impacted all areas of transplant, especially living donor kidney and living donor liver transplant. Deceased donor liver transplant was also impacted due to various reasons such as donors testing positive, hospitals overwhelmed with COVID-19 patients, and potential recipients testing positive for SARS-CoV-2. With a shrinking donor pool, efforts were made to consider SARS-CoV-2-positive potential donors who did not die of COVID-19 or were negative by BAL PCR. Increasing evidence demonstrated minimal risk of SARS-CoV-2 transmission from non-lung donors who tested positive for SARS-CoV-2; however, the risks of donor-derived SARS-CoV-2 from liver donors are still unknown to date [4,5]. We present our experience of two cases in which a liver was transplanted successfully from a brain-dead donor with incidental SARS-CoV-2 infection.

Case report 1

Donor

The donor was an 18-year-old male with no known prior medical history who died of head trauma from a motor vehicle accident. He was unvaccinated against COVID-19 and had an asymptomatic SARS-CoV-2 infection in August 2021. At the time of organ donation, the donor's nasopharyngeal swab was positive for SARS-CoV-2 by PCR with a cycle time (CT) of 38.5. Nasopharyngeal rapid antigen testing and BAL PCR were negative for SARS-CoV-2. Chest x-ray showed bibasilar focal patchy consolidations.

Recipient

The recipient was a 56-year-old male with end stage liver disease (ESLD) due to alcoholic cirrhosis with refractory ascites, hepatic hydrothorax, and hepatic encephalopathy. He had a MELD-Na of 30 and was requiring weekly paracentesis. He had been vaccinated against COVID-19 with an adenovirus vectored vaccine and an mRNA booster. An organ became available in late September 2021. The recipient was number sixteen on the match run list with multiple decline codes related to organ quality or COVID-19. After discussion with the infectious disease specialist and with the patient about the risks and benefits of proceeding or declining the organ offer, we proceeded with liver transplantation. The recipient was negative for SARS-CoV-2 on rapid antigen testing. He underwent an orthotopic liver transplant. He had an uncomplicated postoperative course and was discharged on postoperative day (POD) 8. He is doing well over a year post transplantation.

Case report 2

Donor

24-year-old male with a body mass index of 23 kg/m² with past medical history of mood disorder and suicidal attempt was declared brain dead after a cardiac arrest. The cause of the arrest was unknown and patient had a downtime of 40 min. The donor's nasopharyngeal swab was positive for SARS-CoV-2 by PCR with a CT of 34. Nasopharyngeal rapid antigen testing and BAL PCR were negative for SARS-CoV-2.

Recipient

The recipient was a 44-year-old female with cryptogenic cirrhosis complicated by refractory ascites and portal vein thrombosis that required transjugular intrahepatic portosystemic shunt procedure. Her MELD score at the time of transplant was 35. She was vaccinated against COVID-19 before her transplant with a mRNA vaccine (two doses). An organ became available in December 2021. The recipient was eleventh on the match run list with multiple decline codes related to organ quality or COVID-19. After discussion with the infectious disease specialist and with the patient about the risks and benefits of proceeding or declining the organ offer, we proceeded with liver transplantation. She underwent an orthotopic liver transplantation. Patient had a main portal vein thrombus and a thrombectomy was performed. Transplant was performed in a standard bicaval fashion. Patient tolerated the surgery well and had an uneventful postoperative recovery. She was discharged on POD 8. On POD 12, she was readmitted with low grade fever, sore throat and headache. She was found to be SARS-CoV-2 positive with a CT of 18.8. She received monoclonal antibody treatment with casirivimab-imdevimab and 10 days of remdesivir. She was discharged after 10 days and has been doing well since then. She has recently completed her 9 month follow up. The source of her SARS-CoV-2 exposure was uncertain and could not be confirmed as no family members, close contacts, or healthcare workers involved in her care were known to be symptomatic or SARS-CoV-2 positive. Hence, the source of her COVID-19 remains unclear.

Discussion

The COVID-19 pandemic has substantially impacted the field of liver transplantation. During the initial pandemic wave, hospitals adapted by limiting elective surgery to direct maximum resources to care for critically ill patients [6]. Organ donation and liver transplantation also decreased in number, especially at the beginning of pandemic (first wave) and second wave [7,8]. Due to the life-saving nature of heart, liver, and lung transplantation, these solid organ transplants continued to be performed during the pandemic. There were significant decreases in waitlist additions along with an increase in waitlist deaths in most transplant regions in the United States [9]. Solid-organ transplantation decreased in major European, Asian and North American transplant centers [10]. As the pandemic has evolved, healthcare providers and administrators continue to be challenged with dilemmas including evaluating donors with SARS-CoV-2 infection. As the pool of organs available for transplantation is already scarce, it is imperative to discuss scenarios where organs from deceased brain and cardiac donors with SARS-CoV-2 may be considered for transplantation. Transplantation from deceased donors with asymptomatic or mild SARS-CoV-2 infection can be considered in select cases. It is not clear that potential direct hepatocyte infection by SARS-CoV-2 has significant clinical implications. There is also limited evidence of transmission of SARS-CoV-2 through blood transfusions even in immunosuppressed patients [11,12]. The arguments against using liver donors infected with SARS-CoV-2 include recent studies that SARS-CoV-2 can directly infect hepatocytes through alternative receptors [13,14]. Exposure of healthcare providers during organ procurement and surgical teams is also a concern with potential downstream consequences of exposure and transmission. Liver injury and hepatocyte involvement may occur in COVID- 19 with mechanisms ranging from systemic inflammatory responses to direct infection [13]. Although end-organ involvement is a manifestation of severe COVID 19, the absence of severe symptoms or laboratory abnormalities does not rule out the involvement of solid organs and the accompanied end-organ damage. It can be challenging to fully evaluate the history of prior vaccination and severity of symptoms in deceased donors with severe and rapid deterioration due to COVID-19. Guidance from the American Association for the Study of Liver Diseases (AASLD) recommends that liver donation from potential donors with incidental COVID-19 can be considered with recipient consent [1]. Findings that favor the safety of donation include the lack of infiltrates consistent with COVID-19 on chest imaging and SARS-CoV-2 infection diagnosed within the previous 90 days. Higher CT may suggest lower viral loads or non- infectious viral remains and may be requested in decision making. The urgency of recipient need for transplantation may also be factored into the decision to accept an organ from a SARS-CoV-2-positive donor. Romangoli et al. [15], recently published a report of 10 liver transplants from SARS-CoV-2-positive donors and eight patients remained negative. Two patients became SARS-CoV-2 positive and one of them remained positive for 21 days. One recipient died after transplant; however, that recipient had a MELD of 35 and had COVID-19 with 30 days of pneumonia before transplant.¹⁵Major North American and European societies recommend SARS-CoV-2 nucleic acid testing as part of the routine evaluation of liver donors and recipients. Nasopharyngeal swab testing has an associated false negative rate that must be weighed with presenting signs and symptoms along with imaging [16]. In deceased donors, BAL should be considered for testing as it has a lower false negative rate. To date, there is no consensus on the waiting time and repeat testing requirements before organs are recovered from donors with recently documented SARS-CoV-2 infection. To be on the safe side, we use a CT value of >30 as cut off for accepting SARS-CoV-2-positive organ donors for transplant. A CT value of lower than 30 has been associated with high secondary transmission rates [17]. However, this is an area that is yet to explored in terms of donor acceptance and use of more SARS-CoV-2-positive organs for transplant.

Our case reports show mild, symptomatic posttransplant SARS-CoV-2 positivity in one case and no record of posttransplant SARS-CoV-2 infection in the other case. We looked into all the possible causes of SARS-CoV-2 infection in one of our transplant patients but the cause of this transmission remained uncertain. Nosocomial transmission is possible and most likely, however, the risk of transmission from the donor could not be ruled out especially in the setting of a COVID positive donor and less data available on tissue transmission(liver in this case). A lot of case reports and case series are coming forward from across the world that is helping us understand this disease better, especially in relation to our transplant patients. Every information coming out or getting published is adding to the data pool with regard to the use of such donors [18,19].

Conclusion

Asymptomatic and incidentally diagnosed SARS-CoV-2-positive donors can and should be used for liver transplant in order to increase the donor pool, shorten the wait-time and decrease waitlist mortality. Donor selection can be individualized based on donor and recipient factors. Although the potential impact on the recipient is still not well understood, SARS-CoV-2-positive donors should continue to be used after careful donor selection.

Consent

Informed consent was obtained from both the patients for publication of this case report.

Disclosures

No relevant disclosures.

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.