key: cord-1000150-eshws03z
authors: Belli, Luca S.; Conti, Sara; Polak, Wojciech
title: Reply to the Editor's letter: Tacrolimus use and COVID-19 infection in patients after solid organ transplantation
date: 2021-04-20
journal: Gastroenterology
DOI: 10.1053/j.gastro.2021.04.033
sha: ed184272f8730f7f7544ebea85dcd61d77057d9f
doc_id: 1000150
cord_uid: eshws03z

nan

We read with great interest the letter by Yin et al. [1] where the authors comment the results of our recently published study [2] .

The authors raised some methodological issues on our study design, suggesting a possible selection bias as we included both patients receiving homecare (survival rate of 100.0%, 82.1% received tacrolimus) and those requiring hospitalization (survival rate of 76.0%, 63.7% received tacrolimus) in the analysis. Against this argument we remind that 'place of management' indicates the place with the highest intensity of care required by symptomatic patients during their disease course, and it should be considered as an intermediate outcome between onset of COVID-19 and death/recovery or a proxy for disease progression. If we selected patients based on 'place of management' we would, on the contrary, introduce a selection bias that would affect the assessment of any protective effect of the baseline use of tacrolimus. In the end, tacrolimus was more frequently used in patients receiving homecare who never experienced a worsening of the disease, clearly supporting our finding of a protective effect particularly in younger patients without comorbidities.

A second issue refers to changes of the calcineurin inhibitors (CNI) doses in hospitalized patients.

Of the 57 inpatients who underwent withdrawal of CNI or a 25-50% dose reduction, 18 (31.5%) were on lopinavir therapy, dose modifications being justified by the interference between the two drugs. For the remaining 39 patients the modifications of CNI doses were proportionally distributed between cyclosporine and tacrolimus making any selection bias unlikely. Further 12 of 13 patients who stopped tacrolimus had interstitial pneumonitis requiring O2 supplementation.

An additional issue points to the discordant results between our study and the only other study published on COVID-19 liver transplant patients by Colmenero et al. [3] . In this latter study from We therefore believe that pooling results from various types of solid organ transplants (SOT) may bias the interpretation of the results Having clarified all this, we agree with the conclusions of Yin e al. that tacrolimus is not a risk factor for mortality among all SOT patients with COVID-19. For liver transplant patients, however, the evidence emerging from the only 2 studies published to date, is that there may be some additional benefit. We hope further studies will better clarify this point.

Additional relevant comments come by Ruiz I et al, who suggest that the lack of beneficial effect of Cyclosporin-A/Other group may be explained by the higher prevalence of many confounders such as male gender, older age, longer interval from LT, more comorbidities and MMF use. However, the protective effect of TAC persisted after including all the fore-mentioned confounders in the multivariable analysis, the biological explanation for this finding remaining unclear. In the end we J o u r n a l P r e -p r o o f agree with the conclusions from Ruiz et al that Tacrolimus has a beneficial effect in SARS CoV-2 infection and therefore TAC doses should not be modified. For the time being there is no evidence that shifting from CyclosporineA/other to TAC could be of any benefit, thus it should not be done.

Tacrolimus use and COVID-19 infection in patients after solid organ transplantation

ELITA-ELTR COVID-19 Registry. Protective role of tacrolimus, deleterious role of age and comorbidities in liver transplant recipients with Covid-19: results from the ELITA/ELTR multi-center European study

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients