key: cord-0913900-l5ryl69x
authors: García-Juárez, I.; Campos-Murguía, A.; Tovar-Mendez, V. H.; Gabutti, A.; Ruiz, I.
title: Unexpected better outcome in a liver transplant recipient with COVID-19: a beneficial effect of tacrolimus?
date: 2020-10-10
journal: nan
DOI: 10.1016/j.rgmxen.2020.08.001
sha: e3a22e534edc156185a81b5715e41aad43f4a85e
doc_id: 913900
cord_uid: l5ryl69x

nan

Paradoxically, the LT recipient presented with a better outcome ( fig. 1 ), raising the question of the potentially beneficial effect of tacrolimus.

A 41-year-old man, with no past medical history, arrived at the emergency department swab test for SARS-CoV-2 was positive and treatment with hydroxychloroquine and azithromycin was started. Fever was present during the first two days of hospitalization, and supplemental oxygen delivered by nasal cannula was required for three days. The patient became asymptomatic after the third day and was discharged.

A 64-year-old woman underwent LT in 2018 due to liver cirrhosis secondary to hepatitis C virus (HCV) that was treated with velpatasvir/sofosbuvir. She had a medical history of which is a key player in T cell activation. [5] [6] The interaction with calcineurin inhibits its J o u r n a l P r e -p r o o f phosphatase activity, preventing the nuclear translocation of its substrate, the nuclear factor of activated T cells, and the consequent expression of immunity genes, such as IL-2 and IL-4. In this manner, tacrolimus suppresses the activation of T cells. 5, 7 In addition, tacrolimus has an antiviral effect by binding to the FKBP proteins, with the subsequent inhibition of their peptidyl-prolyl isomerase activity, whose enzymatic activities are posited to promote coronavirus replication. 6, [8] [9] The present proof of concept observation states that liver transplantation recipients may not have worse outcomes, when compared with other patients that have COVID-19 risk factors. We recognize that the intrinsic limitation of this case report is the small sample size, but its originality lies in the fact that it provides evidence of the mechanisms underlying the potentially beneficial effect of immunosuppressants. Said clinical observation must be confirmed in multicenter trials and real-life cohorts. Additional data are needed to better define the group of patients that would receive a strong benefit from immunosuppressive strategies, and in turn, provide better management of transplant recipients through said strategies, during this epidemic.

The present scientific letter fulfills the current bioethical research regulations. It was authorized by the ethics committee of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán". The patients cannot be recognized or identified through the images or data presented in the article. The authors declare that patient anonymity was preserved at all times, and that patient consent was obtained for the publication of the present article. 

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Coronaviruses and immunosuppressed patients. The facts during the third epidemic

COVID-19 in long-term liver transplant patients: preliminary experience from an Italian transplant centre in Lombardy

Epub ahead of print

Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study

Calcineurin is a common target of cyclophilincyclosporin A and FKBP-FK506 complexes

The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors

Inhibitors of the calcineurin/NFAT pathway

Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506

Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir

The authors wish to thank Dr. Oscar Arturo Lozano-Cruz, Dr. José Luis Cardenas-Fragoso, Dr. Daniel Alberto Carrillo-Vazquez, Dr. Alan G. Contreras, and Dr. Nayelli C.Flores-García. The authors also wish to thank Dr. Quentin Nevers and Flora Donati for the critical rereading of the manuscript.Isaac Ruiz is a recipient of fellowship grants from the CHUM Foundation, Montreal,