Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy.

Lorenzo Cavagna,Alessandro Bertani,Emanuele Bozzalla-Cassione,Monica Morosini,Marilena Gregorini,Angela Di Matteo,Tiberio Oggionni,Carlo Vancheri,Valentina Zuccaro,Federica Meloni,Gianluca Sambataro,Patrizio Vitulo,Elena Ticozzelli,Carlo Marena,Annalisa Turco,Veronica Codullo,Stefano Pelenghi,Carlomaurizio Montecucco,Alessandro Biglia,Barbara Cattadori,Maria Cristina Monti,Carlo Pellegrini,Valentina Bonetto,Massimiliano Gnecchi,Elena Seminari,Giovanni Zanframundo,Eleonora Francesca Pattonieri,Teresa Rampino,F Bertuccio ,Angelo Guido Corsico

doi:10.3390/microorganisms8070977

Abstract

The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to 28 April 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48–69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low.

Highlights

Coronavirus disease 2019 (COVID-19) was first reported in China in 2019 and is related to a new strain of coronavirus, called “severe acute respiratory syndrome coronavirus-2” (SARS-CoV-2) [1]
Among the immunosuppressive drugs used for solid organ transplantation [20] and for systemic rheumatic disorders (RMDs) [21], we focused our attention on two calcineurin inhibitors (CNIs): cyclosporine A (Cys) and tacrolimus (TAC)
Most patients were solid organ transplantation recipients, while 54 patients (14%) suffered from RMDs: 42 patients had antisynthetase syndrome (ASSD) with interstitial lung disease (ILD) (78% of RMDs), 2 had idiopathic inflammatory myopathies (IIMs) (4%), 7 had systemic lupus erythematosus (SLE) (12%), and 3 had adult-onset still disease (AOSD) (6%)

Summary

Introduction

Coronavirus disease 2019 (COVID-19) was first reported in China in 2019 and is related to a new strain of coronavirus, called “severe acute respiratory syndrome coronavirus-2” (SARS-CoV-2) [1]. The results published so far are rather contradictory, with authors reporting either mild [6,7,8,9,10,11,12] or severe disease course with high mortality [13,14,15,16,17,18] These differences could be due to the different approaches adopted for therapy management (continuation or interruption of ISTs). Another confusing factor is that ISTs have been proposed as a treatment for the inflammatory phase of COVID-19 [19]. It is difficult to understand whether immunosuppression should be considered a risk factor for a bad prognosis or a possible treatment strategy, and its management in COVID-19 patients is yet to be established

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