key: cord-1005757-2zsugq7m
authors: Koval, Christine E.; Poggio, Emilio D.; Lin, Yi‐Chia; Kerr, Hannah; Eltemamy, Mohamed; Wee, Alvin
title: Early success transplanting kidneys from donors with new SARS‐CoV‐2 RNA positivity: A report of 10 cases
date: 2021-07-23
journal: Am J Transplant
DOI: 10.1111/ajt.16765
sha: ae3e6138cf48e91f45f2803df74bacacdaa7049e
doc_id: 1005757
cord_uid: 2zsugq7m

Transplantation of solid organs from donors with active SARS‐CoV‐2 infection has been advised against due to the possibility of disease transmission to the recipient. However, with the exception of lungs, conclusive data for productive infection of transplantable organs do not exist. While such data are awaited, the organ shortage continues to claim thousands of lives each year. In this setting, we put forth a strategy to transplant otherwise healthy extrapulmonary organs from SARS‐CoV‐2‐infected donors. We transplanted 10 kidneys from five deceased donors with new detection of SARS‐CoV‐2 RNA during donor evaluation in early 2021. Kidney donor profile index ranged from 3% to 56%. All organs had been turned down by multiple other centers. Without clear signs or symptoms, the veracity of timing of SARS‐CoV‐2 infection could not be confirmed. With 8–16 weeks of follow‐up, outcomes for all 10 patients and allografts have been excellent. All have been free of signs or symptoms of donor‐derived SARS‐CoV‐2 infection. Our findings raise important questions about the nature of SARS‐CoV‐2 RNA detection in potential organ donors and suggest underutilization of exceptionally good extrapulmonary organs with low risk for disease transmission.

Since March 2020, over 33 million SARS-CoV-2 infections with more than a half million deaths have occurred in the United States. 1 Despite uncertainties and pandemic-related disruptions, most transplant centers and organ procurement organizations have continued to provide these lifesaving therapies supported by infection prevention practices. 2, 3 Nationwide, only a modest decrease in deceased donor transplantation occurred in 2020 compared to 2019. 4 However, the organ shortage persists with thousands of deaths on the transplant waitlist yearly, including over 4000 deaths while awaiting a kidney transplant in 2020. 5 Those dying from severe COVID-19 are not considered for organ donation. Given the prevalence of infection, however, it was expected that those dying from other causes might also have active SARS-CoV-2 infection. By April 2020, SARS-CoV-2 screening was required for all potential organ donors to avoid the possibility of virus transmission to recipients through transplanted organs and to the medical teams during organ procurement. Those with detectable SARS-CoV-2 RNA have generally not been considered for donation unless there is evidence for successfully resolved infection.

While SARS-CoV-2 infection in the airway of potential donors is prohibitive of lung donation, transplantation of the extrapulmonary organs has been more controversial. An editorial by Kates, et al. published in July 2020 put forth a well-considered argument for use of such organs. 6 Early in the pandemic, most organ procurement organizations considered SARS-CoV-2-infected donors to be ineligible for organ donation. Recent guidance from the Organ Procurement Transplant Network Disease Transmission Advisory Committee suggests balancing the risk for SARS-CoV-2 transmission possible effects on allograft quality and risk to procurement teams with the recipient's risk for mortality and other complications on the waitlist. 7 Still, many centers do not consider allografts from such donors.

Without convincing evidence to date for productive (or transmissible) infection of most transplantable extrapulmonary organs, we put forth a strategy at our center for transplanting such organs from selected donors with SARS-CoV-2 RNA detection on screening. While not restricted to kidneys, our strategy resulted in the following 10 kidney transplants from five deceased donors.

Our strategy included considering all SARS-CoV-2-positive deceased donors with otherwise acceptable donor characteristics and healthy appearing kidneys with good organ function. Lower airway testing was requested and considered reassuring when negative. We aimed to avoid donors with severe COVID-19 or with COVID-related inflammatory syndromes (Figure 1 ). A cycle threshold as a surrogate for viral load was requested but not required. The strategy was approved by our transplant center leadership.

There were no recipient selection criteria other than willingness to accept such an organ. All candidates were explained the risks and benefits of accepting a kidney from a SARS-CoV-2 RNA-positive donor and all provided clinical consent. None of our own center candidates declined an offer. Recipients received standard immunosuppression, including induction with rabbit antithymocyte globulin, prograf, mycophenolate mofetil, and prednisone, and posttransplant care. All were monitored closely for signs of COVID-like illness with plans for chest imaging and SARS-CoV-2 testing when present. Since circulated virus from the kidney would likely infect the lower airway prior to detection in the upper airway, we did not consider upper airway testing to be a helpful screening tool. COVID-specific infection prevention precautions (N95, eye protection in addition to universal surgical precautions) were recommended during organ recovery but not during organ implantation. Recipients were followed as for all our early organ transplant recipients with caregivers using routine surgical masking, eye protection, gloves, and hand hygiene. No added precautions were recommended by Infection Prevention at our institution. Approval from our Institutional Review Board was obtained for preparation and submission of this report.

Since February 2021, seven deceased donors from three different organ procurement organizations were considered by our program.

Two donors were not accepted due to bilateral ground glass pulmonary infiltrates and death from cerebrovascular accidents. Five were accepted for kidney donation. The donor details are summarized in Table 1 . All donors were tested positive for SARS-CoV-2 RNA by nasopharyngeal swab (NPS) polymerase chain reaction (PCR) by a variety of testing platforms after hospital admission and within 3 days of donation. All but donor 3 had additional tests during the index hospitalization that were negative, including three from lower airway specimens within 2 days of donation. None had record of recent COVID-19 or prior positive SARS-CoV-2 testing. However, donor 1 had a detectable SARS-CoV-2 IgG and a reported exposure to infected relatives the month before. None had reported COVID-like symptoms or signs prior to or during admission. None had infiltrates on chest X-ray or computed F I G U R E 1 Factors to consider when accepting extrapulmonary organs from SARS-CoV-2 RNA-positive organ donors to minimize the theoretical and unknown absolute risk for SARS-CoV-2 transmission to recipients and organ procurement teams and to minimize the potential subclinical effect on end organ function from SARS-CoV-2 infection and inflammatory syndromes. All such information may not be readily available or consistently reliable. The boxed region would be considered exceedingly low risk for most recipients by our program tomography scan suggestive of severe COVID-19. Donor 3 tested positive for hepatitis C RNA and had a terminal creatinine level higher than 1.5 mg/dl. A biopsy specimen showed no pathological change. The kidney donor profile index (KDPI) was extremely favorable for three donors. Organ offers were turned down by other transplant centers prior to allocation to our candidates. One donor was administered the SARS-CoV-2 monoclonal antibody on the day of donation. Two donors had other organs allocated elsewhere.

Ten kidneys were accepted for 10 adult recipients. Recipients consented to receive an organ from a "COVID-positive" donor with a low (but not zero) risk for disease transmission and unknown subclinical effects of SARS-CoV-2 infection on organ function. Recipient details are summarized in Table 2 . Transplantation for one recipient was preemptive and the remainder were on dialysis. Median waitlist time was 1251 days with two recipients having short wait times. influenza A outbreaks but the scope and duration of these outbreaks were limited. 16, 17 Nucleic acid from RNA respiratory viruses can be detected in extrapulmonary organs during infection, and influenza A has been shown to infect other organs during fatal infection. 18 However, evidence for donor-derived transmission of any RNA respiratory viruses from extrapulmonary organs is absent. 19 There are few published case reports of extrapulmonary organ transplants from donors with SARS-CoV-2 infection with none resulting in definitive organ-derived COVID-19. [20] [21] [22] Two were living donor liver transplants performed prior to routine testing of donors and recipients.

One donor was mildly symptomatic at donation. A donor recipient pair In this setting, one might also consider risk mitigation strategies.

For example, accepting these organs only for those recipients with some immunologic protection as a result of prior infection or vac- Figure 2 . However, this is not currently clinically practicable for reasons listed in the figure. Given current testing limitations and limited evidence, our approach and recommendations are to monitor our recipients for clinical signs and symptoms of COVIDlike illness and initiate appropriate testing at that time.

We aimed to avoid donors with a possibility of subclinical organ injury that might occur in the setting of severe COVID-19 and did not accept kidneys from two donors with more extensive pulmonary infiltrates and new onset ischemic stroke. Kidney pathologies from autopsy series of those dying from severe disease include endothelial damage, collapsing glomerulopathy, obstructive erythrocyte aggregates of capillaries, and inflammation. 28, 29 Since kidney injury is most likely due to effects of the inflammatory response, it is unlikely in the early phases of infection but not known if it could be present in later phases without common clinical markers. 30 In conclusion, we demonstrated successful short-term outcomes for kidney transplantation from selected donors with detectable SARS-CoV-2 RNA. Recipients experienced no clinical signs of donorderived SARS-CoV-2 infection, and there were no transmission events to organ procurement teams. Longer term follow-up is warranted. That many of our donors were on the exceedingly low end of the risk spectrum for transmissible virus and that other centers turned down, these organs for highly ranked candidates suggest that there is underutilization of otherwise excellent quality organs.

Scientific data that would support restricting or expanding the use of SARS-CoV-2-infected donor organs are eagerly awaited. In the meantime, we advocate for the cautious use of SARS-CoV-2 RNApositive donors for transplantation of most extrapulmonary organs.

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Early success transplanting kidneys from donors with new SARS-CoV-2 RNA positivity: a report of 10 cases