Repeat SARS-CoV-2 testing after recovery. Is a pretransplant PCR necessary?

Abstract

To the Editor: The emergence of SARS-CoV-2 and the clinical syndrome of COVID-19 resulted in a major decrease in transplant volumes during the first months of the pandemic followed by a change in practice, with strict screening and SARS-CoV-2 PCR testing prior to transplant. Protocols required a negative SARS-CoV-2 PCR prior to proceeding with transplantation. Many transplants were delayed nationwide due to persistent positive PCRs in asymptomatic patients, sometimes for months.1UNOS. COVID-19 Resources for Organ Transplants and Donations. https://unos.org/covid/. Published November 3, 2020. Accessed November 9, 2020.Google Scholar Currently the Centers for Disease Control and Prevention does not routinely recommend a test of cure to determine when isolation for COVID-19 can be discontinued.2Centers for Disease Control and Prevention. Duration of Isolation and Precautions for Adults with COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html. Accessed November 9, 2020.Google Scholar For patients with mild to moderate COVID-19, replication-competent virus has not been recovered after 10 days following symptoms.3Bullard J, Dust K, Funk D, et al. Predicting infectious SARS-CoV-2 from diagnostic samples. Clin Infect Dis. 2020. https://doi.org/10.1093/cid/ciaa63.Google Scholar,4Wölfel R Corman VM Guggemos W et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469Crossref PubMed Scopus (4156) Google Scholar Recovery of replication-competent virus between 10 and 20 days after symptom onset has been documented in some patients with severe COVID-19 and immunocompromised patients.5Van Kampen J, van de Vijver D, Fraaij P,. et al. Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants. (Preprint) Medrxiv. 2020. https://doi.org/10.1101/2020.06.08.20125310.Google Scholar Here we report a case of a 64-year-old white female with stage 5 chronic kidney disease secondary to Alport’s syndrome. She works at a nursing home and tested positive for SARS-CoV-2 by the rapid qualitative antigen test (using the Sofia SARS antigen FIA kit) 24 h after developing body aches and fever. She never developed any respiratory symptoms and her fever subsided within 1 day without any specific therapy. Six weeks later, she was called for a deceased donor kidney transplant organ offer. As part of our workup upon admission to the hospital, a nasopharyngeal specimen was collected for SARS-CoV-2 testing, which was positive. Cycle threshold (CT) values on the Roche cobas SARS-CoV-2 assay for the ORF1a/b and E gene targets were 35.5 and 30.3, respectively (for our laboratory a CT of <38 and <45 is considered positive for the respective gene targets). It has been shown that CT values >30 indicate low viral load.6Westblade LF Brar G Pinheiro LC et al.SARS-CoV-2 viral load predicts mortality in patients with and without cancer who are hospitalized with COVID-19.Cancer Cell. 2020; 38 (661-671.e2.)Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Since she was asymptomatic for more than 6 weeks, negative chest X-ray, and had a high cycle threshold on PCR, we believe that this was a detection of residual SARS-CoV-2 RNA in the absence of active infectious viral particles. Given the assessment that active viral replication was unlikely, we proceeded with a kidney transplant with 3 mg/kg of thymoglobulin as induction. After the procedure, the patient was placed in the regular transplant floor without COVID-19 restrictions. She has been maintained on triple immunosuppression therapy as per our standard protocol with prednisone, mycophenolate mofetil, and tacrolimus. Our trough goals have been 7–10 ng/ml for the first month, and 5–7 ng/ml since then. She remains asymptomatic without any fever or signs of infections at a 4-month follow-up from the time of transplantation. This is the first case of a patient with a past history of COVID-19 and detectable SARS-CoV-2 RNA by PCR at the time of kidney transplantation with thymoglobulin induction. A similar scenario was reported in a liver transplant candidate with positive COVID-19 testing at the time of transplant. Patient was asymptomatic and had a prior COVID-19 exposure 6–10 weeks earlier. Patient underwent liver transplant without any reported infectious complications.7Rouphael C, D’Amico G, Ricci K, et al. Successful orthotopic liver transplantation in a patient with a positive SARS-CoV2 test and acute liver failure secondary to acetaminophen overdose. Am J Transplant. 2020. https://doi.org/10.1111/ajt.16330.Google Scholar Our case highlights kidney transplantation may be safely carried out in asymptomatic patients with a persistently positive SARS-CoV-2 PCR. A limitation of our case is the absence of a posttransplant COVID-19 PCR, and a relatively short 4-month follow-up. Based on this case and current literature, our transplant center changed its policy of re-testing patients who have been diagnosed with COVID-19. Patients are placed active on the list if they are 6 weeks from the initial positive COVID-19 and at least 4 weeks without symptoms. Patients will not be tested again with another PCR before transplant if they are within 3 months from the initial positive test. Additional experience in a larger patient group and non-kidney transplantation are needed to determine the safety of this approach. TA is supported by a Mid-America Transplant Clinical Innovation Award and the Foundation of Barnes Jewish Hospital Award. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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