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  • Rosa Emilia Moraes

Covid-19 and Immunosuppression



Different drugs used in the maintenance immunosuppressive regimen of patients undergoing kidney transplantation were analyzed using evidence currently available in the literature. Results indicate that treatment management in the context of Sars-Cov-2 infection must be carefully individualized, as immunosuppression has an independent effect on outcomes.


 

Article: Sandes-Freitas TV, Requião-Moura L, Tedesco-Silva H. Impacto da Imunossupressão na Gravidade da Infecção por Sars-CoV-2 em Transplantados Renais. BJT. 2022.25(04):e0122. https://doi.org/10.53855/bjt.v25i4.474_IN

 

Covid-19 and Immunosuppression: drugs to prevent rejection in kidney transplants influence the outcome of the disease


Patients undergoing a kidney transplant procedure, in the context of infection with the new coronavirus (Sars-CoV-2) generally have a high mortality rate, transmit the virus for a longer time, and have a smaller and less durable immune response to vaccines (REQUIÃO- MOURA et al., 2021).


Immunosuppression is essential to prevent rejection of the transplanted organ, but the drugs used in the treatment directly interfere with the dynamics of any infectious process. This interference varies according to a series of factors related to the mode of action of the pharmaceutical, the stage of infection and the level of severity of the disease, and may even mitigate some cases of lung damage, inhibiting the production of pro-inflammatory cytokines (SANDAL et al., 2021).


Aiming to gather and discuss the findings available in the current literature on the effects of immunosuppressive drugs in modulating the outcomes of infection by Sars-CoV-2 in kidney transplant recipients, researchers from the Federal University of Ceará and the University of São Paulo, linked to reference hospitals in kidney transplants in Brazil, elaborated a narrative review of the current literature, analyzing the results presented in several studies. The article “Impacto da imunossupressão na gravidade da infecção por Sars-CoV-2 em transplantados renaispublished in vol. 25, n. 4, of the Brazilian Journal of Transplantation includes more than seventy references covering the most commonly used immunosuppressive drugs among kidney transplant patients.


Among the aggregate evidence, it remains demonstrated that calcineurin inhibitors (CI) such as cyclosporine and tacrolimus can bring benefits in relation to viral replication and modulation of the inflammatory response, but on the other hand, they have a potential negative effect on the vaccine immune response. Regarding corticoids, the results understood by the surveyed literature indicated controversies. Rabbit antithymocyte globulin, or thymoglobulin (ATG), was considered safe and its application as an anti-rejection treatment should not be postponed.


The mTOR inhibitors (sirolimus and everolimus) have a well-known antiviral effect. In vitro studies have also observed potentially beneficial effects for patients affected by viruses from the Coronaviridae family, in addition to speculation about a potential antifibrotic effect. However, this class of drugs has known pulmonary toxicity, which calls for caution.


Results also point out that the Covid-19 lethality rate in kidney transplant patients undergoing treatment with mycophenolic acid was higher than those using azathioprine and mTOR inhibitors. However, the three substances are considered to be related to the incidence of lymphopenia.

The vaccine-induced immune response and demonstrated or potential drug interactions between immunosuppressants and drugs with proven efficacy in combating Covid 19 were also appreciated in the review, with emphasis on the antiretroviral Ritonavir, which can interfere with the concentration levels of CI and imTOR, as well as high doses of steroids can act to reduce the concentration of tacrolimus.


The study also includes a list of guidelines for the management of immunosuppression during the Sars-CoV-2 pandemic, which summarizes the research findings. As a general conclusion, it appears that the modulatory effects of pharmacological immunosuppression in Covid infection is a subject that still requires clarification, and any change in the treatment regimen that prevents rejection of the transplanted organ must be done with caution, considering all aspects of the evolution of the infectious condition and its prognosis.


 

Read more (References):


Requião-Moura LR, Sandes-Freitas TV, Viana LA, Cristelli MP, Andrade LGM, Garcia VD, et al. High mortality among kidney transplant recipients diagnosed with coronavirus disease 2019: Results from the Brazilian multicenter cohort study. PLoS One. 2021;16(7):e0254822. https://doi.org/10.1371/journal.pone.0254822


Sandal S, Boyarsky BJ, Massie A, Chiang TP, Segev DL, Cantarovich M. Immunosuppression practices during the COVID-19 pandemic: A multinational survey study of transplant programs. Clin Transplant. 2021;35(8):e14376. https://doi.org/10.1111%2Fctr.14376

 

Links


Hospital do Rim (Fundação Oswaldo Ramos)


Hospital Geral de Fortaleza


Brazilian Journal of Transplantation

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