Management of kidney transplant recipients with coronavirus disease 2019.

Abstract

To the Editors, Severe acute respiratory syndrome coronavirus 2 is the formidable viral pathogen of β-coronavirus family that causes coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. It has thus far infected over seven million individuals, and over 0.4 million patients have already succumbed to complications as per the World Health Organization (WHO) situation report – 142 (June 10, 2020).[1] Competent immune system is crucial in determining the prognosis of COVID-19 infection; however, this might not be true for kidney transplant recipients receiving immuno-suppressive regimen. A substantial number of COVID-19 patients demonstrate lymphopenia, and reduced lymphocyte count has been shown to be associated with COVID-19 severity.[2] Pro-inflammatory cytokines such as interleukin-6 (IL-6)and tumor necrosis factor-alpha, part of cytokine storm, are reportedly elevated in critically ill COVID-19 patients, reemphasizing the notion that heightened immune activity might affect morbidity and mortality in COVID-19 and underlining the importance of fine balance between defensive and aggressive host immune activity.[3] Immunosuppressive drugs possess intrinsic ability to impede the physiological function of lymphocytes and/or precipitate lymphopenia. Owing to lack of definite treatment for COVID-19 infection, most of the kidney transplant societies endorse moderation in immunosuppression considering the patient safety. However, this might not be a pragmatic approach for patients with imminent transplant rejection. In the present commentary, we aim to summarize the potential management approaches used in transplant centers for kidney transplant patients diagnosed with COVID-19. Kidney transplant recipients necessitate longterm maintenance immunosuppressive therapy. To prevent kidney allograft rejection at slightly higher risk of transplant infection, the standard clinical practice is to perform therapeutic drug monitoring to ensure safety and efficacy. Given the scarcity of data on management of kidney transplant recipients with confirmed COVID-19, it is plausible to minimize maintenance immunosuppressive therapy. Nonetheless, how much reduction in maintenance immuno-suppressive therapy is needed to contain COVID-19 and simultaneously avoid allograft rejection is yet to be established. Immuno-suppressive drugs, especially calcineurininhi-bitors (CNIs), significantly condense the T-lymphocyte immune response and thereby enhance the risk of unrestrained viral shedding and invasion. Lately, it has been reported in an in vitro study that nonimmunosuppressive derivatives of cyclosporinA can reduce the N protein expression, required for viral reproductive cycle, of human coronavirus 229E.[4] This underscores the possible implication of cyclos-porin A as the ideal CNI for kidney transplant recipients with COVID-19 infection. In vitro data regarding tacrolimus for the aforementioned activity is unavailable. Research reports on kidney transplant recipients with COVID-19 infection are now accumulating.[56789101112] In accordance with the recent literature, elderly kidney transplant patients are at an increased predisposition to develop severe COVID-19 and progress toward death.[13] The initiation and management of patients with immunosup-pressive, immunomodulatory, and antiviral therapy drastically fluctuate between published research reports Table 1. The data related to the use of anticytokine therapy, for instance, anti-IL-6 or complement inhibitors, are also uncertain. Of late, a mega SOLIDARITY trial (ISRCTN83971151) by the WHO is underway that will examine remdesivir, lopinavir-ritonavir, lopinavir-ritonavir + interferon-β1a, and chloroquine or hydroxychloroquine treatment options for COVID-19 patients. Kidney transplant patients are also part of the SOLIDARITY trial, and we are optimistic that something groundbreaking will show up soon. It is noteworthy to mention here that a number of antiviral medicines interact with CNIs, and meticulous drug monitoring for cyclosporin A or tacrolimus would be required. Finally, transplant physicians need to be wary of patient characteristics while making decisions regarding treatment of COVID-19 in kidney transplant recipients.Table 1: Case reports of immunosuppressive and COVID-19 treatment regimen used in kidney transplant recipients with COVID-19 infection.In summary, evidence on optimal treatment regimen for kidney transplant recipients to treat COVID-19 and avoid transplant rejection is not well-established. The present commentary was based on recent case reports evidence and warranted further substantiation in future work. Conflict of interest None declared.