COVID-19 AMALGAM

 

Impact of COVID-19 pandemic on transplantation

 

 

E Steyn^{I, II}; S Al-Benna^III

^IDivision of Surgery, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, South Africa
^IIRenal Transplant Centre, Netcare Christiaan Barnard Memorial Hospital, South Africa
^IIIDivision of Plastic and Reconstructive Surgery, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, South Africa

 

 

End-stage organ failure is estimated to affect more than six million people worldwide.¹ More than one and a half million people live with a transplanted organ worldwide.¹ In 2018, transplant systems across the world enabled around 150 000 patients to benefit from a kidney, heart, lung, liver, or other solid organs.¹ In South Africa, over 500 patients receive a transplant every year, but 4 300 patients remain on waiting lists.² Only 0.2% of the population are registered organ donors and there are high death rates while on the waiting list for transplantation.² This vast discrepancy between need and provision is compounded by the fact that elective transplant programs were paused at the onset of the COVID-19 pandemic. Healthcare providers, institutions and patients are concerned about the potential effect the pandemic will have on organ donation and transplantation.³ The evolving epidemic has led to reduced activities in organ donation and transplantation across South Africa. Similarly, transplantation programmes have been suspended in other countries because of scarce resources (especially ICU beds) and concerns regarding immunosuppressive induction regimens.⁴ In the USA, 71.8% of surveyed physicians reported full suspension of live donation kidney transplant programmes, and 80.2% of deceased donor kidney transplant programmes were operating with restrictions.⁴

Transplant programs, like other surgical services, face a scarcity of critical care resources, healthcare personnel and the challenge of preventing in and out of hospital post-transplant COVID-19 infection.⁵ The already-complex risk and benefit assessment for each donor and transplant recipient is clouded by a paucity of data on the effects of contracting COVID-19 during the transplantation event or during follow-up. Transplant patients are among the highest risk groups for developing severe COVID-19 infection, due to comorbidities and immune suppression.³⁶

In our view, the following considerations should be born in mind as the transplant community adapts to the current situation and to the increased transplantation activity as lockdown eases.

Firstly, existing transplant patients should be cared for to the best of our ability. It is encouraging that reports suggest that transplant patients may not be at higher risk of contracting COVID-19 if proper social distancing and preventive measures are employed.⁶ A recent report of 87 heart transplant recipients in Wuhan, China, noted that social distancing coupled with other preventive measures led to a COVID-19 infection rate no higher than that of the general population.^6,7 Isolation and social distancing, however, may be problematic in certain low resourced, densely populated communities in South Africa.

Distance from a transplant centre has been associated with increased mortality, and prolonged lockdown will further hinder access to care, and amplify existing inequalities in the transplantation process.⁸ The increasing presence of COVID-19 in communities requires sustained efforts from transplant programmes to encourage ongoing post-transplant protective self-isolation. Transplant telehealth programmes may reduce costs, shorten time to initial evaluation and waitlist placement, improve quality of life, and decrease re-admissions following transplantation.⁸ As with any change in care delivery, virtual telemedicine services must not create or promote disparities for the most vulnerable populations.⁸

Secondly, there is limited information on if or how immunosuppression should be altered if the recipient becomes infected with COVID.^3,6,9-11 In the event of COVID-19, most clinicians would continue calcineurin inhibitors (CNI) and glucocorticoids but stop the antiproliferative drugs, while balancing the risk of rejection. However, in newly transplanted patients, or a graft rejection, this may not be possible. In-vitro studies show non-immunosuppressive derivatives of cyclosporine A inhibits the N-protein of human coronavirus 229E, preventing viral replication.⁹ Consequently, cyclosporin may be the preferred CNI during the COVID-19 pandemic. No data are available on whether tacrolimus derivatives or metabolites exhibit similar in-vitro activity However, the lymphopenia as well as T-lymphocyte dysfunction caused by CNIs may potentially enable viral invasion and proliferation. Similarly, due to their lymphocyte depletion effect, avoidance of anti-thymoglobulin or alemtuzumab induction regimens is prudent. Many patients with severe COVID-19 develop lymphopenia, which is a poor prognostic factor. Should transplant recipients develop severe COVID-19 requiring mechanical ventilation, CNIs and antiproliferative drugs should be immediately withdrawn and glucocorticoid doses should be increased.¹⁰

Significant efforts have been made by the health systems, industry and government, to strengthen the overall ICU capacity at national level to cope with severely ill COVID-19 patients.⁵ Despite this, access to critical care resources for non-COVID-19 cases remains based on local policy and resources. Transplantation and other disciplines may need to make the argument for access to the limited number of ICU beds (approximately 7 195 across the country) particularly for non-renal transplant patients who cannot be sustained on options such as dialysis.⁵ The lack of ICU resources will exacerbate the inability to accommodate brain dead potential donors, which will further reduce the donor pool. Assessment of potential donors would require a rapid and accurate test for the presence of COVID-19, with low false negatives. It is unclear with the varying waiting times for results in the state sector how this could be facilitated. Other detrimental factors are the logistic challenges for donor organ procurement and transplant surgery, due to containment measures, travel restrictions, and transplant healthcare professionals being engaged with the treatment of COVID-19 patients.

During the COVID-19 outbreak, transplant programmes should cautiously weigh up the value, sensitivity and costs of additional screening tests, the potential risk of postoperative complications and the unpredictability of outcomes, against the potential benefits of optimal organ utilisation, especially for high priority liver and heart recipients. At this time, supportive care is all we have to combat this virus in solid organ transplant recipients.³⁶¹⁰¹¹ Every effort should be undertaken to ensure that all transplant candidates and recipients may safely access healthcare systems and their resources in the current pandemic scenario. The pandemic will have ongoing effects in the long term such as increasing waiting lists, resulting in increased mortality and worse preoperative conditions.¹² It is therefore of great importance to identify the right time to re-open and re-establish transplant programmes. The considerations discussed in this article remain to be validated in future studies.

ORCID

Ε Steyn © https://orcid.org/0000-0002-8090-1559

S Al-Benna https://orcid.org/0000-0003-4079-9286

 

REFERENCES

1. WHO Task Force on Donation and Transplantation of Human Organs and Tissues. Transplantation. Available from: https://www.who.int/transplantation/donation/taskforce-transplantation/en/. Accessed 13 May 2020.         [ Links ]

2. Organ Donation Foundation. Statistics. Available from: https://www.odf.org.za/info-and-faq-s/statistics.html. Accessed 13 May 2020.         [ Links ]

3. Michaels MG, La Hoz RM, Danziger-Isakov L, et al. Coronavirus disease 2019: Implications of emerging infections for transplantation. Am J Transplant. 2020;20(7):1768-72. https://doi.org/10.1111/ajt.15832. [Epub ahead of print.         [ Links ]].

4. Boyarsky BJ, Po-Yu Chiang T, Werbel WA, et al. Early impact of COVID-19 on transplant centre practices and policies in the United States [published online ahead of print, 2020 Apr 13]. Am J Transplant. 2020. https://doi.org/10.1111/ajt.15915.         [ Links ]

5. Evans S. SA's healthcare system has only around 3 000 critical care hospital beds available ... and it is not enough. News24. Available from: https://m.news24.com/SouthAfrica/News/sas-healthcare-system-has-only-around-3-000-critical-care-hospital-beds-available-and-it-is-not-enough-20200320. Accessed 13 May 2020.         [ Links ]

6. Ren ZL, Hu R, Wang ZW, et al. Epidemiological and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China: a descriptive survey report. J Heart Lung Transplant. 2020 39(5): 412-117.. https://doi.org/10.1016/j. healun.2020.03.008.         [ Links ]

7. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.         [ Links ]

8. Ross K, Patzer RE, Goldberg DS, et al. Sociodemographic determinants of waitlist and post transplant survival among end-stage liver disease patients. Am J Transplant. 2017;17:2879-89. https://doi.org/10.1111/ajt.14421.         [ Links ]

9. Ma-Lauer Y, Zheng Y, Malesevic M, et al. Influences of cyclosporin A and non-immunosuppressive derivatives on cellular cyclophilins and viral nucleocapsid protein during human coronavirus 229E replication. Antiviral Res. 2020;173:104620.         [ Links ]

10. Kronbichler A, Gauckler P, Windpessl M, et al. COVID-19: implications for immunosuppression in kidney disease and transplantation. Nat Rev Nephrol. 2020;16:365-7. https://doi.org/10.1038/s41581-020-0305-6.         [ Links ]

11. Zhong Z, Zhang Q, Xia H, et al. Clinical characteristics and immunosuppressants management of coronavirus disease 2019 in solid organ transplant recipients. Am J Transplant. 2020 Apr. https://doi.org/10.1111/ajt.15928.         [ Links ]

12. Al-Benna S. Concepts of management of plastic surgery services during the coronavirus disease 2019 pandemic [published online ahead of print, 2020 Jul 13]. Eur J Plast Surg. 2020;1-2. https://doi.org/10.1007/s00238-020-01704-1.         [ Links ]