We report a case of a liver transplant performed in a patient with a history of SARS-CoV-2 infection who presented with a positive polymerase chain reaction test for SARS-CoV-2 on the day of transplant. The transplant procedure was performed without complications, and the patient did not develop symptoms after the initiation of immunosuppression. We also reviewed the literature for similar cases. The emergence of SARS-CoV-2 has forced the medical community to continuously adapt protocols to the current situation. Prudence is needed in immuno-compromised patients, and clinical experience is being built day by day. Thus, a positive polymerase chain reaction test for SARS-CoV-2 in a recipient should not always prevent a liver transplant.
Key words : COVID-19, Immunosuppression, Pandemic
The emergence of SARS-CoV-2 infection has had an impact in many aspects of daily clinical practice. Transplant recipients are immunocompromised patients who are at high risk for severe SARS-CoV-2 infection. However, some patients cannot have postponed transplantation, and, in some settings, mortality rates while on the wait list have been shown to be higher than mortality rates after transplant.1 Although there is some experience in solid-organ transplant candidates with laboratory-confirmed SARS-CoV-2 who have had kidney transplants, reports are limited in liver transplant candidates.2
Here, we present a case of a patient with positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test from a nasopharyngeal swab just before liver transplant. Our report also includes a systematic literature review in PubMed in which we searched the terms “COVID-19” OR “SARS-CoV-2” OR “liver’’ OR “transplantation.” We selected all published cases of solid-organ transplant performed in SARS-CoV-2-positive recipients. These previously published cases were analyzed and contrasted with our case. Our recipient was aware of the results of tests and provided written informed consent for the transplant procedure. The study was exempt from institutional review board approval.
We present the case of a 70-year-old woman with medical history of arterial hypertension, type 2 diabetes mellitus, and obesity with body mass index (in kilograms divided by height in meters squared) of 38. She was listed for liver transplant in June 2020 (Child-Pugh class B, Na-Model for End-Stage Liver Disease score of 14) due to alcohol-related cirrhosis. In September 2020, she was diagnosed with SARS-CoV-2 infection after development of upper respiratory tract symptoms. She displayed no pulmonary infiltrates in her chest radiography examination. She did not need hospitalization and recovered without complications. Meanwhile, she was suspended from the transplant list according to the current recommendations from the Spanish National Transplantation Organization (ONT).3
The patient was readmitted on the wait list in mid-January 2021 when viral RNA was undetectable in up to 2 nasopharyngeal swabs, performed over a 1-week period, by a transcription-mediated amplification (TMA)-based assay (Aptima SARS-CoV-2 on Panther System [Hologic], with index values of 332 and 304). Her anti-SARS-CoV-2 seropositive status was confirmed by detection of total antibodies against anti-nucleocapsid protein (Elecsys Anti-SARS-CoV-2, Cobas 8800 system [Roche], with an index value of 172) and of immunoglobulin G antibody anti-spike S1/S2 (Liaison SARS-CoV-2 S1/S2 immunoglobulin G [IgG] on Liaison XL analyzer [DiaSorin], with a value of 292 UA/mL).
In April 2021, a compatible donor was offered. In accordance with the local protocol, a nasopharyngeal swab for SARS-CoV-2 detection was repeated, which tested positive by RT-PCR (Xpert Xpress SARS-CoV-2, GeneXpert, Cepheid, with negative E gene but N2 gene cycle threshold [Ct] of 41.7). A rapid lateral flow chromatographic immunoassay for detection of both nucleocapsid and spike antibodies (Assure FaStep COVID-19, Grifols) was performed that detected IgG but not immunoglobulin M. This resulted in the need for a decision of whether to pursue the liver transplant. After evaluation of the risk-benefit in a patient seropositive for SARS-CoV-2, we decided to perform the liver transplant.
The patient received the liver from a deceased donor who had tested negative for SARS-CoV-2. The transplant procedure went well, and the patient was admitted to the intensive care unit. Immunosup-pression was started with corticosteroid bolus (methylprednisolone 200 mg twice per day), basiliximab (2 doses of 40 mg separated 4 days), and tacrolimus (9 mg). On posttransplant day 3, she developed acute kidney and respiratory failure due to liquid overload that required the initiation of continuous venovenous hemodiafiltration. On posttransplant day 5, her chest radiography examination revealed a condensation affecting the right inferior lobe; thus, piperacillin-tazobactam was initiated.
SARS-CoV-2 RNA was detected in a nasop-haryngeal aspirate by the Aptima assay (index value of 798), which was also confirmed by the Xpert assay. However, she tested negative for E gene and positive for N2 gene, showing a high Ct value (38.1). SARS-CoV-2 was not detected in her tracheal aspirate. Because of the low viral load, screening for the VOC 202012/01 variant of SARS-CoV-2 was inconclusive by an assay based on the spike gene target failure (TaqPath COVID-19 RT-PCR kit, Thermo Fisher Scientific). Enterobacter cloacae was isolated in the tracheal aspirate; thus, piperacillin-tazobactam was changed to meropenem.
The patient had a good clinical outcome. Moreover, graft function was always correct. On posttransplant day 10, a nasopharyngeal swab for SARS-CoV2 was repeated that showed a negative result (Table 1).
Current ONT recommendations state that transplant candidates with positive screening for SARS-CoV-2 should be temporally excluded from the transplant list until 14 days after initiation of symptoms. Moreover, a negative PCR is recommended to be readmitted on the wait list; however, in cases of persistent positivity, an individual case assessment is recommended.3
Our seropositive, asymptomatic patient presented with newly detected SARS-CoV-2 at the time of transplant. Because the patient had no symptoms suggestive of SARS-CoV-2 infection at that time, had remained seropositive by 2 serological tests, and had 2 molecular methods that suggested low viral RNA copies in the respiratory tract (index TMA value of 798, with negative tests for E gene and positive tests for N2 gene with Ct value of 38.1 by RT-PCR), we decided to proceed with the transplant. The clinical outcomes supported this decision because the patient did not develop a symptomatic SARS-CoV-2 infection.
During the COVID-19 pandemic, different molecular techniques have been used for SARS-CoV-2 detection based on nucleic acid amplification. Some, such as those based on TMA, do not provide quantitative values that correlate with viral load, although they do provide information on its viability. In this sense, as considered in the case reported here, a PCR-based assay can make an indirect approximation of the amount of virus in the initial respiratory sample. Even so, it should be highlighted that the Ct value is directly conditioned by the quality of the sample, the collection conditions, and the PCR technique used.
Although index TMA values of about 600 by Aptima and Ct values close to 40 or even discrepant with other viral target correspond to low viral RNA copies, several studies have shown that RNA detection is not always related to the excretion of viruses capable of replicating, even when Ct values are above 24.4,5 In fact, Lang and colleagues6 described the performance of a lung transplant in a patient with post-COVID-19 terminal respiratory failure with serial positive specimens for SARS-CoV-2 and Ct values greater than 30 but with specimens not able to infect in vitro Vero cell isolation culture at 7 days.
In liver transplantation, there are very few reports of patients with positive molecular tests for SARS-CoV-2 undergoing transplant with good clinical outcomes. There are 3 reports in patients who required liver transplant due to acute liver failure not related to SARS-CoV-2 infection itself.7-9 In those cases, the recipients were considered to have limited risk factors for poor outcomes due to SARS-CoV-2. They were young and with mild symptoms. Of note, they would have died waiting for a negative RT-PCR as recommended by current transplant society guidelines. On the other hand, there are 2 cases in which liver transplant was performed from donors with SARS-CoV-2 infection to recipients also positive, as some transplant organizations have established such an option.10,11 Again, both recipients were asymptomatic for SARS-CoV-2 infection. A previous report from India communicated 3 living donor liver transplants with positive SARS-CoV-2 tests in donors as well as in recipients. However, all were at least 14 days from the time of diagnosis and were asymptomatic at time of transplant.12 Finally, Okubo and colleagues13 reported a case of a liver transplant in an asymptomatic SARS-CoV-2-infected patient with persistent RT-PCR positivity for 40 days.
The case reported here is another experience supporting the individual evaluation of patients who are on the waiting list and who have laboratory-confirmed SARS-CoV-2 infection. Currently, there is sustained community transmission that makes the situation described in our case to be expected with increasing frequency. To discard these recipients can compromise their access to transplant therapy, as well as expose them to an increased risk of morbidity and, ultimately, mortality. Thus, we consider that the option of proceeding with transplant could be considered even when RT-PCR is positive for SARS-CoV-2, especially when the candidate is asymptomatic, the positivity of RT-PCR is with elevated Ct values, and anti-SARS-CoV-2 IgG antibodies are detected.
This case is an example supporting that sometimes protocols do not address all possible situations and that a careful multidisciplinary evaluation should be performed. Moreover, it breaks a barrier on the possibility to move forward with transplant in asymptomatic SARS-CoV-2-seropositive patients when viral RNA detection shows high Ct values.
Volume : 20
Issue : 3
Pages : 321 - 324
DOI : 10.6002/ect.2021.0387
From the 1Infectious Diseases Department, the 2Microbiology Department, the 3Intensive Care Department, and the 4Internal Medicine-Hepatology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
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 declarations of potential conflicts of interest.
Corresponding author: Oscar Len Abad, Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Passeig de la Vall d’Hebron 119-129, 08035 Barcelona, Spain
Table 1. Microbiological results performed during the patient course.