Introduction

The effect of COVID-19 infection was initially profound worldwide, reducing the number of organ transplants in all countries with organ transplant services. In the United States, the reduction of deceased and living donors initially in 2020 exceeded 50%. The fear was the transmission of COVID-19 as a passenger with the transplanted organ.

However, as time elapsed, experience and the appropriate collection of data have enabled organs to be recovered from deceased donors and transplanted successfully without the evidence of COVID-19 transmission to the recipient.

Importantly, testing all donors for SARS-CoV-2 by nucleic acid amplification tests (NATs) from a donor respiratory sample within 72 hours, but ideally as close as possible to organ recovery, was a key component for detection of genetic viral material by NATs, RNA tests, and polymerase chain reaction (PCR) tests. As testing availability increased, molecular testing of donor respiratory samples was universally performed in the United States as of the end of April 2020.¹ Universal SARS-CoV-2 testing of donor respiratory samples could decrease the risk of unrecognized infection and therefore minimize the risk of donor transmission.

The Center for Disease Control Review

Utilizing this approach, the initial Center for Disease Control (CDC) investigations (between March 2020 and March 2021) evaluated 40 potential deceased donors who had positive NAT results of the upper respiratory tract without prior known history of COVID-19.² The upper respiratory sample was derived from the airway above the trachea, inclusive of a nasopharyngeal swab, nasal midturbinate swab, or oropharyngeal swab.

Three of these 40 donors were infected with SARS-COV-2; 5 non-lung transplant recipients of organs from these donors did not develop clinical evidence of SARS-Cov-2.

The initial CDC investigations during this period also evaluated 3 deceased donors who tested negative for SARS-CoV-2 in an upper respiratory tract sample, but 2 donors were subsequently determined, retrospectively, to be positive for SARS-CoV-2 in a lower respiratory tract sample, and 1 donor prospectively tested positive for SARS-CoV-2 in a lower respiratory tract sample at the time of organ implantation.^2-4 The lower respiratory tract sample was obtained from the trachea or below, inclusive of sputum, tracheal aspirate, bronchial suction or wash, and bronchoalveolar lavage.

The lung recipients from these donors developed COVID-19 severe infection after transplant, 1 of whom died. There were 6 non-lung organ recipients, none of whom developed evidence of COVID-19 infection.

As a result of these CDC investigations, the Organ Procurement and Transplantation Network (OPTN) implemented a policy effective at end of May 2021 to require all organ procurement organizations of the United States to test lower respiratory samples for SARS-CoV-2 for all potential lung donors and report those results prior to the transplant of deceased donor lungs.⁵ Viral testing by NAT of at least 1 sample from the respiratory tract was also to be obtained within 3 days of procurement.

The use of NAT of samples from blood, urine, or stool was not recommended. There was insufficient evidence to support its use, so SARS-CoV-2 antibody testing of donors was not recommended as a marker for assessment of safety or potential transmission risk of COVID-19 to recipients.

International Experience

In November 2020, the Italian Transplant Authority allowed donors with COVID-19 infection to be considered for urgent-need transplant candidates who were known to be positive for SARS-CoV-2 infection or who had a history of COVID-19. Five of the donors had a positive lower respiratory tract NAT result for SARS-CoV-2 at the time of organ recovery without a history of COVID-19.⁶ There was no evidence of SARS-CoV-2 infection in the recipients after transplant.

The United Kingdom National Health Service Blood and Transplant body mandates testing for SARS-CoV-2 RNA in upper respiratory and lower respiratory specimens in all potential deceased donors.⁷ Between April 2020 and January 2021, there were 987 deceased donors who enabled 2469 transplants, of which 75 were lung transplants, with no evidence of donor-derived COVID-19.

The apprehension of the transmission of COVID through organ transplant was mitigated as a result of these reports.

Review by the Ad Hoc Disease Transmission Advisory Committee of the Organ Procurement and Transplantation Network

The OPTN Ad Hoc Disease Transmission Advisory Committee developed a summary of evidence on donor SARS-CoV-2 testing and organ recovery from donors with a history of COVID-19 in 2021, which was last updated in April 2022.⁸ This summary of evidence was based on published literature as well as OPTN and CDC data. The guidance includes taking into account the recipient’s risk of mortality as well as the risk of transmission to the surgical procurement and implantation teams. In terms of donor characteristics, the guidance recommends assessment of the timing of when the donor first developed COVID-19 infection to determine whether the donor’s positive test for SARS-CoV-2 represents active infection compared with resolved infection, the severity of infection, the risk of microvascular events in the allograft secondary to COVID-19, and whether the cause of the donor’s death is attributable to COVID-19.

Donors with active COVID-19 infection carry an unknown risk of disease transmission and other noninfectious sequelae in the allograft such as microvascular disease. The US Food and Drug Administration in December 2020 permitted laboratories to report the cycle threshold values for molecular diagnostic tests for SARS-CoV-2. A cycle threshold value indicates the number of amplification cycles needed for detection of the nucleic acid target during the amplification process. High cycle threshold values generally correlate indirectly with lower SARS-CoV-2 viral loads and low cycle threshold values with higher viral loads. However, the CDC and Food and Drug Administration currently recommend against the use of cycle threshold values for assessment of an individual’s risk of infectivity.^9,10

Recovery of Organs from Deceased Donors with a History of Resolved COVID-19

There were 5 important points to acknowledge:

(1) Deceased donors with resolved COVID-19 and a negative NAT result for SARS-CoV-2 at the time of donor evaluation are not known to transmit infection.

(2) Donors with resolved COVID-19 and a positive NAT result for SARS-CoV-2 at the time of donor evaluation are unlikely to transmit COVID-19 to non-lung organ recipients.

(3) Donors with a history of mild COVID-19 more than 10 days and less than 21 days after the date of disease onset and resolution of symptoms are unlikely to transmit COVID-19 to non-lung organ recipients.

(4) Donors with resolved COVID-19 and a positive NAT result for SARS-CoV-2 at 21 to 90 days after the date of disease onset are unlikely to transmit infection. A positive NAT result for SARS-CoV-2 in this scenario likely represents nonviable virus.

(5) Donors with resolved COVID-19 and a positive NAT result for SARS-CoV-2 more than 90 days after the date of disease onset may reflect reinfection which may place the recipient at risk for disease transmission.

Organ Utilization

Ongoing efforts to optimize protocols for donor SARS-CoV-2 testing and organ evaluation are critical to support safe transplants and increase organ utilization during this ongoing pandemic. Multiple case reports and case series have shown a lack of transmission of SARS-CoV-2 from donors with resolved COVID-19 infection. Sixty-five recipients received a kidney (n = 45), liver (n = 14), or heart (n = 6) transplant from 55 donors with a positive PCR test for SARS-CoV-2, whose first positive test was a median of 54 days (range, 3-140 days) prior to organ procurement.^11-22 None of these transplant recipients developed symptomatic COVID-19 transmission.

Although it has not been eliminated, the effect of COVID-19 on transplant activity has lessened with time in 2021 and early 2022. Deceased donor transplants have continued during more recent COVID-19 surges.23 Forty-nine organs from 18 deceased donors with a PCR test positive for SARS-CoV-2 from LiveOnNY were transplanted between March 2020 and November 2021.24 New England Donor Services has recovered 43 organs from 18 donors with a PCR test positive for SARS-CoV-2 between January and March 2022, of which 34 organs were transplanted (28 kidneys, 4 livers, and 2 hearts).

The OPTN Ad Hoc Disease Transmission Advisory Committee compared donors who were positive for SARS-CoV-2 by PCR test within 21 days of procurement versus donors without a positive PCR test for SARS-CoV-2 between May 27, 2021, and January 31, 2022.25 Organs from a  total of 617 COVID-19-positive donors were recovered. COVID-19-positive donors recovered represented only 1.7% to 3.5% of donors between end of May and August 2021 as contrasted by COVID-19-positive donors representing 5% to 7% of donors between September 2021 and December 2021. In January 2022, 21% of donors recovered had a positive SARS-CoV-2 PCR test. For non-lung organs, the utilization and discard rates were similar for donors who had tested positive for COVID-19 compared with all other donors.

Conclusions

As the prevalence of individuals with recovered COVID-19 infection increases, determining when organs from these donors can be safely transplanted is an urgent priority. Donor organs from patients whose NAT results are positive for SARS-CoV-2 are increasingly being used over time, and presently more than 90% of organ procurement organizations in the United States are offering organs from deceased donors who test positive for COVID-19 infection with similar outcomes in recipients to non-COVID-19-positive donor organs. The guidelines presented in this review will facilitate the safe recovery and transplant of organs from donors with a prior history of COVID-19 or active COVID-19 infection.

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