Re-engaging Organ Transplantation in the COVID-19 Era

June 5, 2020

The novelty of the viral pandemic is over. The urge to “get back to normal” is gaining momentum and no less so in the field of transplantation. Living donation remains curtailed and deceased donor transplantation has not resumed pre-COVID activity. While the ASTS Strikeforce is equally fatigued with the current state of healthcare, we want to stress transplant specific observations relating to resumption of clinical transplantation.

The premise of all clinical care (not just transplantation) is to do more good than harm. Transplantation puts an emphasis upon the “gift of life” and its tremendous benefit, but we have also learned to live with the morbidity of a large surgical procedure and immunosuppression in very sick people. The SARS-CoV-2 virus adds an important wrinkle to the long list of risks in transplant recipients. Unfortunately, at this time a precise description of transplant COVID-19 risk to the recipient and the system in general is not known. Acquiring COVID-19 disease as a transplant recipient is reported to have increased mortality (15-30%), often atypical presentations and probably a longer duration of shedding/altered viral kinetics. (Pereira MR et al AJT 2020, Akalin E et al NEJM 2020).

It appears quite likely that COVID-19 disease is going to persist in our communities for the foreseeable future and we are going to have to adapt to its continued presence. With these caveats, the Strike Force gives the following considerations of performance of transplant related procedures for the membership:

PRE-TRANSPLANT SURGERY MANAGEMENT:       

  • Waitlist: Social distancing, hand hygiene, masks in public areas and usual preventive measures for avoidance of a respiratory infection continue to be the mainstay. When and how to broadly open clinics and out-patient facilities must occur in concert with community and hospital practice. Remaining uninfected while in a state with multiple morbidities should remain a priority. An inactivated waitlist candidate infected with COVID-19 should not be reactivated until the PCR is negative.
  • Pre-operative evaluation for a recipient of a deceased donor organ: When an organ becomes available, an individual with active COVID-19 infection should not be transplanted. Transplant surgery/immunosuppression is not advised in symptomatic or asymptomatic infected individuals with COVID-19. We have discussed issues related to organ donation in the COVID era in a prior statement. It is recommended that each program know the community prevalence of viral disease and assess a potential candidate’s risk of exposure and disease acquisition prior to transplantation. While no specific factor is exclusatory, the answers should be included in the decision making process.
    • Do they live/know anyone with COVID-19?
    • Do they have (had) a fever, cough, sore throat, diarrhea, change of smell or taste?
    • Been practicing social distancing? Stay at home? Work exposure?
    • Have they been using respiratory precautions (mask, frequent hand hygiene) when in public spaces? How often in public spaces?

    Informed consent is an important element of the waitlist management/ patient selection and reentry of surgical procedures. The people who will receive a transplant need to know that post-transplant avoidance of COVID-19 infection is required. Updated consent documents and processes should be provided.

    PCR testing for the SARS-CoV-2 virus immediately (within 12 hours) prior to organ transplantation should be performed and if positive, the procedure should be postponed until/if the recipient clears the virus.

  • Pre-operative evaluation of the live donor: The live donation procedure must be planned so the potential donor knows the medical and psychosocial risks associated with undergoing the donation procedure. Of course the live donor does NOT need to donate for health reasons and the procedure must performed in a manner to mitigate COVID-19 exposure and complications. The Wuhan experience of 34 asymptomatic, but PCR+ for SARS-CoV-2, patients who proceeded with general surgery procedures must make the donation team pause: 100% developed COVID-19 pneumonia, 40% ICU admission and 20% died. (Lei S et al Lancet https://doi.org/10.1016/j.eclinm.2020.100331). An individual who is PCR+ for COVID-19 should not be a live organ donor. The risk is unacceptable. Knowing the community prevalence of COVID-19 is central to decision-making and processes in the hospital, as there is probably a significant number of individuals in the community with subclinical infection. Specific strategies will be dependent upon risk of asymptomatic infection. There is some suggestion that individuals who have anti-COVID antibodies and are PCR negative are relatively immune to subsequent infection, although confirmation remains to be demonstrated. We would propose that a medically suitable, COVID-19 PCR- donor with no history of cough or exposures go into self-isolation for a minimum of 7 days, but preferably 7-14 days. Two days prior to proposed donation, another COVID-PCR should be negative, and on the day of surgery a rapid COVID-19 PCR, temperature check, and CXR should be normal. Use of local prevalence data, exposure, and precaution history is crucial to making “better” decisions. In the absence of data, judgment must rule. The duration of self-isolation may be a point of contention, and the donor team must balance the significant negative outcomes of operating upon an asymptomatic, infected person with donor inconvenience. However, donor protection is central to responsible evaluation and performance of live organ donation. It is recommended that a special informed consent form of COVID-19 risk appreciation be generated (sample being utilized Intermountain Medical Center in Salt Lake City).
  • Pre-operative evaluation of the recipient of a live donated organ: Unlike deceased donor recipients, knowledge of the transplant procedure date is known. As with the live donor, a negative COVID-19 PCR, self-isolation for 7-14 days followed by a pre-procedure negative PCR, CXR, and normal exam will provide support that the transplant procedure is performed on an uninfected individual.

POST-TRANSPLANT SURGERY MANAGEMENT:

  • Hospital Patient Placement: Nosocomial acquisition of COVID-19 has occurred in transplant patients. Strategies to minimize risk of transmission to patients (and hospital workers) should adhere to local protocols. Uninfected transplant patients should NOT be co-located with people hospitalized for COVID-19 infection. All patients admitted to a transplant floor should have a negative COVID PCR screen. This is particularly important for individuals admitted from the community for peri-transplant events, as asymptomatic infection is recognized. The ability to cohort a hospitalized “uninfected transplant patient” away from COVID-infected patients may not be possible in specialty areas such as ICU, step-down units, procedure suites, dialysis, etc. However, understanding and minimizing risk is central to the safe performance of transplant care. Depending upon community prevalence, screening of hospital staff is prudent. Barring repetitive, universal testing, adherence to respiratory barrier protection and hand hygiene is mandatory.
  • Immunosuppression regimens: There is no clear guidance to optimize immunosuppressive regimens. Severe COVID infection is associated with lymphopenia and an extreme proinflammatory response. This has formed the basis for immunomodulatory therapies (in contrast to antiviral therapy). The two issues for the transplant immunosuppression are:
    • Induction: In locales with a high prevalence of COVID-19, T cell depleting agents should be avoided, if possible. The major patient risk is the acquisition of COVID disease during the time of intense immunosuppression. Unfortunately, there is no good data, but the NY experience suggests that the duration of cell depletion (thymoglobulin vs alemtuzumab) acute infection is worse. The underlying recipient age and frailty must also be factored into the decision-making for the intensity of induction. Strategies and goals should provide for durable transplant engraftment and avoidance of infectious disease. Much of the latter involves non-immunosuppressive regimens and are social dependent.
    • COVID-19 Infection in the transplanted patient: When an immunosuppressed transplant recipient becomes infected with SARS-CoV-2, a variety of approaches to immunosuppression has been proposed. Severe COVID infection is associated with lymphopenia and significant proinflammation (IL-6 CRP, procalcitonin...). Reports from Europe and US have typically reduced or stopped antimetabolites when disease becomes severe. In less severe cases, little to no modulations have occurred. Treatment of rejection (cellular or humoral) with active COVID-19 infection has not been reported, but lymphocyte depletion seems like a bad idea. There has been little to suggest that one immunosuppressive strategy is more successful than another. There is room for significant investigation on the interface between alloimmunosuppression and the immune response induced by the virus. As it appears that the virus is going to part of the long-term landscape, it is crucial that the community develop rational strategies to address alloimmunosuppression in the context of antiviral responses.
  • Post-transplant care: The transplant patient is more likely to acquire COVID infection from the community and family than from within the hospital. Education relating to the need for prevention of respiratory infections requires repeated emphasis. Planning for disruption in immediate peri-transplant care is crucial depending upon the prevalence of disease in the recipient locale and the recipient’s living conditions. Early after transplant, a contingency plan should exist for the primary care provider. They may need to be especially cautious and self-isolate in order to provide necessary care.
  • Recipient testing COVID positive, outpatient: Transplant recipients have been observed to have a protracted period of PCR positive test results, often over a month of continual positivity. In order to minimize the risk to others, as long as a patient has detectable PCR product in the airway secretions, they should remain in self-isolation. The risk to the community of an asymptomatic viral shedder is considerable.

It is imperative that the transplant community find a way to provide safe transplant care in the age of a ubiquitous respiratory virus. We will cohabitate with this virus for the foreseeable future. Despite best attempts to prevent a live donor acquisition of COVID-19 and subsequent death, it is likely to happen. The Strike Force recommends that each program performing live donation update its donor disaster plan to include the possibility of death from COVID-19 infection. There are far too many unknowns in this clinical scenario, but there is enough known that we can proceed.