Successful simultaneous pancreas and kidney transplant in a patient post–COVID-19 infection

To the editor:

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 1 ¹). 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 1.

COVID-19 PCR and antibody test results

	April 19, 2020	July 2, 2020	July 3, 2020	July 9, 2020	July 13, 2020	July 16, 2020	July 23, 2020	July 30, 2020
SARS-CoV-2 RNA by RT-PCR	Positive	Negative	Negative	Negative	Negative	Negative	Negative
CoV-2, total index (reference range <1.0 S/Ca)		19.3				22.7	31.4	26.3
CoV-2, total Ab (IgG and/or IgM)		Reactive				Reactive	Reactive	Reactive
SARS-CoV IgG Ab		Reactive		Nonreactive	Nonreactive	Nonreactive	Nonreactive	Nonreactive
SARS-CoV IgG index (<1.0 S/Ca)		1.09		0.35	0.31	0.36	0.42	0.31

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.

^aS/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

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.^{2 , 3} 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.^{4 , 5} 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.⁶ 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.⁷ In a smaller study conducted by Zhang et al.,⁸ 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.⁹ 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.^{10 , 11} 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.