Successful simultaneous pancreas and kidney transplant in a patient post–COVID-19 infection
Authors: Neeraj Singh, Srijan Tandukar, Gazi Zibari, Muhammad Saad Naseer, Hosein S. Amiri, Milagros D. Samaniego-Picota
Journal: Kidney International (2020)

The coronavirus disease 2019 (COVID-19) pandemic has slowed down the solid organ transplantation worldwide. Although we have heard of few solid organ transplants having been performed in patients recovered from COVID-19 infection, none has been reported yet. We present a patient who underwent a simultaneous pancreas and kidney transplantation after recovering from COVID-19 and is doing well close to 2 months post-transplantation. A 66-year-old Caucasian woman with end-stage renal disease secondary to insulin-dependent type 2 diabetes mellitus was called in to undergo simultaneous pancreas and kidney transplantation. On admission, we found that 3 months earlier she had been diagnosed with COVID-19 with fever and cough but had recovered completely while in self-quarantine at home. On her admission, she had stable vitals and physical exam was unremarkable. A COVID-19 antibody test was positive for IgG, and COVID-19 rapid polymerase chain reaction (PCR) test was negative on 2 occasions a day apart (Table 11Instructions for Use CoV2T.https://www.fda.gov/media/136967/downloadDate accessed: August 7, 2020Google Scholar). Other laboratory parameters were unremarkable. The chest X-ray and computed tomography scan of the lungs showed no lung abnormalities. The patient underwent simultaneous pancreas and kidney transplantation successfully from a COVID-19–negative donor and had an uneventful post-transplant course. Her serum creatinine trended down to 0.8 mg/dl, and she came off insulin by day 4 post-transplant. She received 3 reduced doses of rabbit anti-thymocyte globulin (Thymoglobulin; Sanofi-Genzyme, Cambridge, MA) 1 mg/kg/d for induction along with intravenous methylprednisolone taper. She was discharged on postoperative day 5 on mycophenolate mofetil 500 mg twice a day, extended-release tacrolimus (Envarsus XR; Rottendorf Pharma GmbH, 59320 Ennigerloh, North Rhine-Westphalia, Germany) 6 mg once a day (target tacrolimus level 7–9 ng/ml), and oral prednisone taper. The patient has remained asymptomatic with no signs of repeat COVID-19 infection 7 weeks after her transplant.Table 1COVID-19 PCR and antibody test resultsApril 19, 2020July 2, 2020July 3, 2020July 9, 2020July 13, 2020July 16, 2020July 23, 2020July 30, 2020SARS-CoV-2 RNA by RT-PCRPositiveNegativeNegativeNegativeNegativeNegativeNegativeCoV-2, total index (reference range <1.0 S/CaS/C, signal for test sample/signal at cutoff value. VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack (Ortho-Clinical Diagnostics, Inc., Rochester, NY).1)19.322.731.426.3CoV-2, total Ab (IgG and/or IgM)ReactiveReactiveReactiveReactiveSARS-CoV IgG AbReactiveNonreactiveNonreactiveNonreactiveNonreactiveNonreactiveSARS-CoV IgG index (<1.0 S/CaS/C, signal for test sample/signal at cutoff value. VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack (Ortho-Clinical Diagnostics, Inc., Rochester, NY).1)1.090.350.310.360.420.31Ab, antibodies; COVID-19, coronavirus disease 2019; PCR, polymerase chain reaction; RT-PCR, reverse-transcriptase polymerase chain reaction; SARS-CoV-2; severe acute respiratory syndrome coronavirus 2.a S/C, signal for test sample/signal at cutoff value. VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack (Ortho-Clinical Diagnostics, Inc., Rochester, NY).1Instructions for Use CoV2T.https://www.fda.gov/media/136967/downloadDate accessed: August 7, 2020Google Scholar Open table in a new tab Ab, antibodies; COVID-19, coronavirus disease 2019; PCR, polymerase chain reaction; RT-PCR, reverse-transcriptase polymerase chain reaction; SARS-CoV-2; severe acute respiratory syndrome coronavirus 2. There were several considerations before proceeding with her transplantation. First, had she successfully cleared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? The detection of COVID-19 by reverse transcriptase-PCR may yield false-negative tests.2Xiao A.T. Tong Y.X. Zhang S. False-negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: rather than recurrence.J Med Virol. 2020; 92: 1755-1756Crossref PubMed Scopus (383) Google Scholar,3Tahamtan A. Ardebili A. Real-time RT-PCR in COVID-19 detection: issues affecting the results.Expert Rev Mol Diagn. 2020; 20: 453-454Crossref PubMed Scopus (828) Google Scholar This uncertainty in test results is further complicated by reports of confirmed reverse transcriptase-PCR–positive COVID-19 cases who recovered from the illness, tested negative on repeat reverse transcriptase-PCR but again tested positive afterward, bringing into question whether this was a repeat infection or whether the preceding test results were, in fact, falsely negative.4Zhang J.-F. Yan K. Ye H.-H. et al.SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standards for discharge.Int J Infect Dis. 2020; 97: 212-214Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar,5Lan L. Xu D. Ye G. et al.Positive RT-PCR test results in patients recovered from COVID-19.JAMA. 2020; 323: 1502-1503Crossref PubMed Scopus (898) Google Scholar Our patient had no symptoms or signs of infection, COVID-19 PCR was negative on two occasions a day apart, and a COVID-19 antibody test was positive. Second, could she have developed a chronic COVID-19 carrier state, and if infection would relapse post-transplant? Many (nonretrovirus) RNA viruses like hepatitis C can establish "within host" persistent infections that occasionally lead to chronic or reactivated disease.6Randall R.E. Griffin D.E. Within host RNA virus persistence: mechanisms and consequences.Curr Opin Virol. 2017; 23: 35-42Crossref PubMed Scopus (72) Google Scholar Chronic COVID-19 carrier state has not been reported yet. Our patient exhibited no symptoms or signs of chronic organ dysfunction and since her transplant, multiple SARS-CoV-2 PCRs have stayed negative. Third, will positive SARS-CoV-2 antibodies protect her from repeat infection? There have been reports of prolonged coexistence of anti–SARS-CoV-2 IgG along with the positive reverse transcriptase-PCR for SARS-CoV-2, raising the possibility of variable level of immunity provided by the antibodies.7Wang B. Wang L. Kong X. et al.Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients.J Med Virol. 2020; 92: 1684-1689Crossref PubMed Scopus (73) Google Scholar In a smaller study conducted by Zhang et al.,8Zhang W. Du R.H. Li B. et al.Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes.Emerg Microbes Infect. 2020; 9: 386-389Crossref PubMed Scopus (1332) Google Scholar both IgM and IgG antibodies were detected in all 39 patients infected with SARS-CoV-2 after 5 days of disease onset. In a report of 149 convalescent individuals with COVID-19 who recovered, authors found that most convalescent plasmas collected an average of 39 days after the onset of symptoms do not contain high levels of neutralizing activity.9Robbiani DF, Gaebler C, Muecksch F, et al. Convergent antibody responses to SARS-CoV-2 infection in convalescent individuals. bioRxiv. https://doi.org/10.1101/2020.05.13.092619. Accessed August 26, 2020.Google Scholar Transplant patients who are on long-term immunosuppression may have attenuated immunity, putting them at risk of atypical presentations, delayed or missed diagnoses, and higher morbidity and possible higher mortality with COVID-19 compared with the general population.10Pereira M.R. Mohan S. Cohen D.J. et al.COVID-19 in solid organ transplant recipients: initial report from the US epicenter.Am J Transplant. 2020; 20: 1800-1808Crossref PubMed Scopus (631) Google Scholar,11Fishman J.A. Infection in organ transplantation.Am J Transplant. 2017; 17: 856-879Crossref PubMed Scopus (480) Google Scholar We lowered the dose of induction and maintenance immunosuppression in our patient to retain the positive anti–SARS-CoV-2 antibodies. Although her total antibodies (IgG and IgM) have persisted until the time of last follow-up, IgG antibodies became negative at 1-week follow-up post-transplant. In conclusion, this case study suggests that it may be reasonable to proceed with solid organ transplant in waitlist candidates if they have recovered completely from COVID-19 with no evidence of active infection, after confirming 2 consecutively negative PCR tests, and with positive SARS-CoV-2 antibody levels. The role of SARS-CoV-2 antibodies in providing protection is unclear, and levels may fall off rapidly post-transplant probably due to immunosuppression. Patients must be advised to continue to take safety precautions post-transplant.