Understanding the Impacts of COVID-Positive Organ Transplants

Transplants Throughout the Pandemic

“Back in March of 2020, sectors all over society shut down, and we experienced that in transplantation,” said Jason Goldman, MD, MPH, and infectious disease physician at the Organ Transplant and Liver Disease Center at Providence Swedish Hospital in Seattle, WA. “Transplant volumes dipped considerably. But thankfully, they recovered relatively quickly by that summer. Healthcare across many different therapeutic areas also suffered, and elective or semi-elective care got deferred.”

A study published in Transplant Proceedings in 2022 noted an overall 17.5% decline in deceased donations worldwide. While these rates varied for each organ and in each country, kidney transplants had the most significant reduction at 20.9%, and heart transplants had a minor decline at 8%. The lags caused unfavorable outcomes for many of those awaiting organs.

Goldman explained that these delays in care contributed to delayed assessments for transplants and overall transplant delays. In turn, these transplant delays contributed to higher wait-list mortality rates.

“There are higher death rates among transplant recipients from COVID compared to the general population, and that's been shown in multiple different ways as well,” noted Goldman. “Throughout the pandemic, programs have been wary of handling it and have done different mitigation strategies to try to serve the wait list population that needs transplants, but it's been curtailed in different ways during the pandemic.”

Early pandemic policies urged providers to avoid solid organ transplants (SOT) from donors with active or recent COVID-19 due to the uncertainty surrounding the virus’s transmissibility. In 2021, the CDC and the Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network (OPTN) noted three cases of SARS-CoV-2 transmission through a lung transplant due to a lower respiratory tract infection in the donor that was not identified by the upper respiratory tract testing — such as a nasal swab — that was conducted before transplant.

Goldman explained that this only occurred from lung donors to transplant recipients, accounting for two cases. After identifying these cases, in May 2021, the OTPN recommended lower respiratory testing for all potential lung donors.

“At that point, the OPTN and the DTAC committee recommended an emergency policy where any lung donor had to have a lower respiratory tract test because what happened in those cases is the upper respiratory tract, or the nasal swab, was negative, but the lower respiratory tract, like a bronchoscopy with a wash, was positive. At that time, there was no mandatory policy on any SARS-CoV-2 testing,” he added.

In their publication, Goldman and his colleagues state, “From the three sentinel donors who transmitted SARS-CoV-2 to the lung recipients, none of the six nonlung organ recipients developed COVID-19, opening the possibility to utilize SAR-CoV-2 infected donors for non-lung SOT.” This conclusion was the baseline of their retrospective study on COVID-positive transplants.

Impacts of COVID-Positive Transplants

Goldman and his colleagues conducted a retrospective study analyzing available data from the national OTPN registry and organ procurement organizations (OPOs). This study set out to determine whether a SARS-CoV-2 can be transmitted through transplants, clarifying whether transplanting organs from a donor who had a recent positive SARS-CoV-2 nucleic acid test (NAT) could have more benefits than the risk of donor-derived transmission events (DDTE).

Study Design

“This study analyzed all cases where the donor had a positive SARS-CoV-2 test in either the upper or lower respiratory tract,” explained Goldman. They looked at testing 21 days before donation and compared that to all donors who did not have a positive test.

The donor populations were divided into two categories: those with a recent positive test and those without. The researchers did not account for a positive test more than 21 days before donation, meaning that the negative group may have included patients with a positive test before the 21-day threshold. The researchers then examined significant outcomes after the transplant, including death and graft loss, which often requires a repeat transplant or — for kidney patients — returning to dialysis.

Study Results

“My team and I looked at over a thousand transplant recipients from donors testing positive. So that's a sizable number where I think we can get some accurate estimates from that big group,” noted Goldman.

As part of the study, the researchers looked at 776 SARS-CoV-2 NAT+ transplants and 11,730 SARS-CoV-2 NAT– transplants. The positive kidney transplants resulted in two deaths (0.3%) and six graft losses (0.8%). Comparatively, NAT-negative kidney transplants resulted in 0.7% of patients dying and 1.6% of patients experiencing graft loss.

For liver transplants, the researchers looked at 316 positive transplants and 5,483 negative transplants. According to the publication, the difference in the rates of graft loss between the two groups was insignificant — 3.8% for positive transplant patients and 3.5% for negative transplant patients. Additionally, the death rate was only 0.9% higher in NAT+ recipients than NAT– recipients.

NAT+ heart transplant patients had a death rate of 2.8% and a graft loss rate of 3.8% after 30 days. Meanwhile NAT– heart transplant patients had a death rate of 2.7% and a graft loss rate of 2.9% after 30 days.

Finally, the 11 NAT+ recipients had no deaths or graft losses for lung transplants. Conversely, the 1,597 NAT– recipients had a 2.6% death rate and a 2.8% graft loss rate.

Goldman revealed that the study did not include enough small bowels to accurately understand whether a small bowel transplant could be a transmission source.

“But at least for kidney, liver, and heart transplants, it does not seem to be transmitted through transplantation,” said Goldman. “Hopefully, that will encourage more OPOs to continue to pursue the donors of people who are testing positive for SARS-CoV-2. We hope to see more transplants from SARS-CoV-2-positive donors in the future because we think the outcomes will likely be quite equivalent.”

Caveats

Despite the promising data collected through this study, Goldman discussed multiple limitations with LifeSciencesIntelligence. First, he notes that the study only examined patients 30 days after transplantation instead of a more extended period. “The research doesn’t clarify, for instance, if there's higher graft loss beyond 30 days,” remarked Goldman.

Additionally, he explained that, because of time constraints and other limitations, the research could not determine whether receiving an organ from a SARS-CoV-2 NAT+ donor could cause post-COVID conditions to manifest in the recipient.

“Clinicians care about many things other than death and graft loss, such as people's overall health and general well-being. There are still some theoretical risks to this kind of transplant. SARS-CoV-2 can cause some clotting disorders or endothelial dysfunction where the virus attacks the lining of the blood vessels,” continued Goldman. “It's possible that there are some more subtle outcomes that we're not measuring. Further research needs to happen in this area to understand if there are other longer-term outcomes that we haven't identified related to the use of donors with SARS-CoV-2 or recent SARS-CoV-2.”

The threats of long-COVID or post-COVID conditions are a critical concern. They can contribute to a worsened quality of life. Additionally, a CDC report published in December 2022 estimated that 3,544 deaths throughout the pandemic had been related to long-COVID. With these concerns in mind, future research may include a follow-up with those who had a NAT+ transplant.

Despite these concerns and limitations, Goldman concluded, “People are dying on the transplant wait list all the time, so that might be an acceptable risk to assume because the alternatives of staying on the wait list are frequently worse.”