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

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

doi:10.3390/microorganisms8070977

Cited by 46 publications

(47 citation statements)

References 28 publications

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“…Experimental evidence suggested that CNIs, both cyclosporine and tacrolimus, inhibited viral replication of SARS-CoV through the inhibition of peptidyl-prolyl cis-trans isomerases [ 38 , 39 ]. A study of 14 patients with organ transplantation in Italy showed that clinical course of COVID-19 patients who received CNIs was generally mild and CNIs did not negatively affect the patients' outcome [ 40 ]. In our cohort, all patients received CNIs as maintenance immunosuppressants.…”

Section: Discussionmentioning

confidence: 99%

Severe acute kidney injury in COVID-19 patients is associated with in-hospital mortality

et al. 2020

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Although the lungs are major targets for COVID-19 invasion, other organs—such as the kidneys—are also affected. However, the renal complications of COVID-19 are not yet well explored. This study aimed to identify the incidence of acute kidney injury (AKI) in patients with COVID-19 and to evaluate its impact on patient outcomes. This retrospective study included 704 patients with COVID-19 who were hospitalized at two hospitals in Daegu, Korea from February 19 to March 31, 2020. AKI was defined according to the serum creatinine criteria in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The final date of follow-up was May 1, 2020. Of the 704 patients, 28 (4.0%) developed AKI. Of the 28 patients with AKI, 15 (53.6%) were found to have AKI stage 1, 3 (10.7%) had AKI stage 2, and 10 (35.7%) had AKI stage 3. Among these patients, 12 (42.9%) recovered from AKI. In the patients with AKI, the rates of admission to intensive care unit (ICU), administration of mechanical ventilator (MV), and in-hospital mortality were significantly higher than in patients without AKI. Multivariable analysis revealed that old age (Hazard ratio [HR] = 4.668, 95% confidence interval [CI] = 1.250–17.430, p = 0.022), high neutrophil-to-lymphocyte ratio (HR = 1.167, 95% CI = 1.078–1.264, p < 0.001), elevated creatinine kinase (HR = 1.002, 95% CI = 1.001–1.004, p = 0.007), and severe AKI (HR = 12.199, 95% CI = 4.235–35.141, p < 0.001) were independent risk factors for in-hospital mortality. The Kaplan-Meier curves showed that the cumulative survival rate was lowest in the AKI stage 3 group (p < 0.001). In conclusion, the incidence of AKI in patients with COVID-19 was 4.0%. Severe AKI was associated with in-hospital death.

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Section: Discussionmentioning

confidence: 99%

Severe acute kidney injury in COVID-19 patients is associated with in-hospital mortality

et al. 2020

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“…Anti-inflammatory drugs have been proposed as possible approaches and it has been suggested that immunosuppressive therapy may mitigate the manifestations of COVID-19. 5,6 Mesenchymal stem cells (MSCs) possess immunomodulatory properties as demonstrated by numerous in vitro and animal model studies. These effects are mediated by cytokines and soluble factors able to modulate the systemic but also the tissue inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

“…As there are no specific therapeutics for treating COVID‐19, in particular for the most severe cases complicated by ARDS or acute fulminant myocarditis, new innovative therapeutic approaches are urgently needed. Anti‐inflammatory drugs have been proposed as possible approaches and it has been suggested that immunosuppressive therapy may mitigate the manifestations of COVID‐19 5,6 . Mesenchymal stem cells (MSCs) possess immunomodulatory properties as demonstrated by numerous in vitro and animal model studies.…”

Section: Introductionmentioning

confidence: 99%

Human mesenchymal stromal cells do not express ACE2 and TMPRSS2 and are not permissive to SARS-CoV-2 infection

Avanzini

Mura

Percivalle

et al. 2021

Stem Cells Translational Medicine

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Anti‐inflammatory and immune‐modulatory therapies have been proposed for the treatment of COVID‐19 and its most serious complications. Among others, the use of mesenchymal stromal cells (MSCs) is under investigation given their well‐documented anti‐inflammatory and immunomodulatory properties. However, some critical issues regarding the possibility that MSCs could be infected by the virus have been raised. Angiotensin‐converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) are the main host cell factors for the Severe Acute Respiratory Syndrome‐Coronavirus 2 (SARS‐CoV‐2) entry but so far it is unclear if human MSCs express or do not these two proteins. To elucidate these important aspects, we evaluated if human MSCs from both fetal and adult tissues constitutively express ACE2 and TMPRSS2 and, most importantly, if they can be infected by SARS‐CoV‐2. We evaluated human MSCs derived from amnios, cord blood, cord tissue, adipose tissue and bone marrow. ACE2 and TMPRSS2 were expressed by the SARS‐CoV‐2‐permissive human pulmonary Calu‐3 cell line but not by all the MSCs tested. MSCs were then exposed to SARS‐CoV‐2 wild strain without evidence of cytopathic effect. Moreover, we also excluded that the MSCs could be infected without showing lytic effects since their conditioned medium after SARS‐CoV‐2 exposure did not contain viral particles. Our data, demonstrating that MSCs derived from different human tissues are not permissive to SARS‐CoV‐2 infection, support the safety of MSCs as potential therapy for COVID‐19. © AlphaMed Press 2020 Significance statement Human mesenchymal stromal cells (hMSCs) are currently under investigation for the treatment of COVID‐19. However, the potential safety profile of hMSCs in this context has never been defined since none has described if they express ACE2 and TMPRSS2, the main host cell factors for SARS‐CoV‐2 entry, and if they can be infected by SARS‐CoV‐2. We provide the first evidence that ACE2 and TMPRSS2 are not expressed in hMSCs derived from both adult and fetal human tissues and, most importantly, that hMSCs are not permissive to SARS‐CoV‐2 infection. These results support the safety of MSCs as potential therapy for COVID‐19.

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“…Since overactivated immune responses can be one of the causes of organ damage, the anti-inflammatory effects of immunosuppression can be protective, reducing the cytokine storm related to complications in COVID-19 [ 26 ]. In this context, it has been described that immunosuppressive therapy with calcineurin inhibitors in patients with solid organ transplantation or systemic rheumatic diseases promotes a clinical course in SARS-CoV-2 infection, which is generally mild, and with an apparently low risk of superinfection [ 27 ]. In addition, immunosuppression has not been evaluated as a risk factor for SARS or MERS [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report

Gozzi-Silva

Benard²,

Alberca³

et al. 2021

TropicalMed

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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.

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

Cited by 46 publications

References 28 publications

Severe acute kidney injury in COVID-19 patients is associated with in-hospital mortality

Severe acute kidney injury in COVID-19 patients is associated with in-hospital mortality

Human mesenchymal stromal cells do not express ACE2 and TMPRSS2 and are not permissive to SARS-CoV-2 infection

SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report

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