On February 19, 2020, the first confirmed case of Coronavirus disease 2019, known as COVID-19, was identified in Iran. Afterward, the disease spread rapidly throughout the country. Some of the cases were asymptomatic, some had mild to severe symptoms, and some of them died. Transplant patients are highly at risk due to long-term immunosuppressive therapy, and precise treatment approaches are needed to not only cure the disease but also protect graft function.
This study reports two kidney transplant patients with COVID-19 pneumonia, both of whom showed respiratory and gastrointestinal symptoms. High cyclosporine and tacrolimus trough levels were observed despite initial dose reduction. After a treatment program containing reduced immunosuppressant dose and the addition of pulsatile hydrocortisone, these patients recovered effectively. We also discuss the importance of drug-drug interactions related to COVID-19 treatment protocol medications, especially with immunosuppressants, in these patients.
In conclusion, frequent monitoring of the trough levels of calcineurin and mammalian target of rapamycin inhibitors during hospitalization is recommended since it helps to determine the ideal treatment and prevent serious clinical toxicity.
- Michaels MG, La Hoz RM, Danziger-Isakov L, Blumberg EA, Kumar D, Green M, et al. Coronavirus disease 2019: implications of emerging infections for transplantation. Am J Transplant. 2020;20(7):1768-72. doi: 10.1111/ajt.15832. [PubMed: 32090448].
- Naesens M, Kuypers DRJ, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009;4(2):481-508. doi: 10.2215/cjn.04800908. [PubMed: 19218475].
- Cossart AR, Cottrell WN, Campbell SB, Isbel NM, Staatz CE. Characterizing the pharmacokinetics and pharmacodynamics of immunosuppressant medicines and patient outcomes in elderly renal transplant patients. Transl Androl Urol. 2019;8(Suppl 2):S198-213. doi: 10.21037/tau.2018.10.16. [PubMed: 31236338].
- Ju CR, Lian QY, Zhang JH, Qiu T, Cai ZT, Jiang WY, et al. Recommended prophylactic and management strategies for severe acute respiratory syndrome coronavirus 2 infection in transplant recipients. Chronic Dis Transl Med. 2020;6(2):87-97. doi: 10.1016/j.cdtm.2020.02.003. [PubMed: 32363045].
- Meziyerh S, Zwart TC, van Etten RW, Janson JA, van Gelder T, Alwayn IP, et al. Severe COVID‐19 in a renal transplant recipient: A focus on pharmacokinetics. Am J Transplant. 2020;20(7):1896-901. doi: 10.1111/ajt.15943. [PubMed: 32337790].
- Bartiromo M, Borchi B, Botta A, Bagalà A, Lugli G, Tilli M, et al. Threatening drug‐drug interaction in a kidney transplant patient with Coronavirus Disease 2019 (COVID‐19). Transpl Infect Dis. 2020;22(4):e13286. doi: 10.1111/tid.13286. [PubMed: 32279418].
- Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395(10223):473-5. doi: 10.1016/S0140-6736(20)30317-2. [PubMed: 32043983].
- Clarke A, Stein C, Townsend M. Drug-drug interactions with HIV antiretroviral therapy. US Pharm. 2008;33(4): HS-3-21.
- Ventura-Aguiar P, Campistol JM, Diekmann F. Safety of mTOR inhibitors in adult solid organ transplantation. Expert Opin Drug Saf. 2016;15(3):303-19. doi: 10.1517/14740338.2016.1132698. [PubMed: 26667069].
- Jain AB, Venkataramanan R, Eghtesad B, Marcos A, Ragni M, Shapiro R, et al. Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients. Liver Transpl. 2003;9(9):954-60. doi: 10.1053/jlts.2003.50171. [PubMed: 12942457].
- van Maarseveen EM, Rogers CC, Trofe-Clark J, Van Zuilen AD, Mudrikova T. Drug–drug interactions between antiretroviral and immunosuppressive agents in HIV-infected patients after solid organ transplantation: a review. AIDS Patient Care STDS. 2012;26(10):568-81. doi: 10.1089/apc.2012.0169. [PubMed: 23025916].
- Vogel M, Voigt E, Michaelis HC, Sudhop T, Wolff M, Türler A, et al. Management of drug‐to‐drug interactions between cyclosporine A and the protease‐inhibitor lopinavir/ritonavir in liver‐transplanted HIV‐infected patients. Liver Transpl. 2004;10(7):939-44. doi: 10.1002/lt.20165. [PubMed: 15237382].
- Finielz P, Gendoo Z, Chuet C, Guiserix J. Interaction between cyclosporin and chloroquine. Nephron. 1993;65(2):333. doi: 10.1159/000187506. [PubMed: 8247209].
- Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis. 2020;34:101623. doi: 10.1016/j.tmaid.2020.101623. [PubMed: 32179124].
- Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99. doi: 10.1056/NEJMoa2001282. [PubMed: 32187464].