tacrolimus and Coronavirus-Infections

Human coronaviruses (HCoVs) seriously affect human health by causing respiratory diseases ranging from common colds to severe acute respiratory diseases. Immunophilins, including peptidyl-prolyl isomerases of the FK506-binding protein (FKBP) and the cyclophilin family, are promising targets for pharmaceutical inhibition of coronavirus replication, but cell-type specific effects have not been elucidated. FKBPs and cyclophilins bind the immunosuppressive drugs FK506 and cyclosporine A (CsA), respectively.. Primary human bronchial epithelial cells (phBECs) were treated with CsA, Alisporivir (ALV), FK506, and FK506-derived non-immunosuppressive analogs and infected with HCoV-229E. RNA and protein were assessed by RT-qPCR and immunoblot analysis. Treatment with the same compounds was performed in hepatoma cells (Huh-7.5) infected with HCoV-229E expressing. Both CsA and ALV robustly inhibited viral replication in all models; both compounds decreased HCoV-229E RNA in phBECs and reduced luminescence in HCoV-229E-RLuc-infected Huh7.5 and SARS-CoV-1-RLuc replicon-transfected HEK293. In contrast, FK506 showed inconsistent and less pronounced effects in phBECs while strongly affecting coronavirus replication in Huh-7.5 and HEK293. Two non-immunosuppressive FK506 analogs had no antiviral effect in any infection model.. The immunophilin inhibitors CsA and ALV display robust anti-coronaviral properties in multiple infection models, including phBECs, reflecting a primary site of HCoV infection. In contrast, FK506 displayed cell-type specific effects, strongly affecting CoV replication in Huh7.5 and HEK293, but inconsistently and less pronounced in phBECs.

Topics: Coronavirus; Coronavirus 229E, Human; Coronavirus Infections; Cyclophilins; Cyclosporine; HEK293 Cells; Humans; Immunosuppressive Agents; Luciferases, Renilla; Pharmaceutical Preparations; RNA; Tacrolimus; Tacrolimus Binding Proteins

Topics: Aged; Betacoronavirus; Cobicistat; Colchicine; Coronavirus Infections; COVID-19; Cytokines; Darunavir; Drug Combinations; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lopinavir; Male; Middle Aged; Mycophenolic Acid; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tacrolimus; Transplant Recipients; Treatment Outcome

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.

Topics: Betacoronavirus; Ceftriaxone; Coronavirus Infections; COVID-19; Cytokines; Glomerulonephritis, IGA; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tacrolimus; Treatment Outcome

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.

Topics: Adult; Antiviral Agents; Betacoronavirus; C-Reactive Protein; Ciliopathies; Cobicistat; Common Cold; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A Inhibitors; Darunavir; Deprescriptions; Drug Combinations; Drug Interactions; Enzyme Inhibitors; Fatigue; Female; Glucocorticoids; Graft Rejection; Humans; Hydroxychloroquine; Immunocompromised Host; Immunosuppressive Agents; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Transplantation; Leber Congenital Amaurosis; Lopinavir; Methylprednisolone; Optic Atrophies, Hereditary; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severity of Illness Index; Tacrolimus

Coronavirus Disease 2019 (COVID-19) is currently a pandemic with a mortality rate of 1%-6% in the general population. However, the mortality rate seems to be significantly higher in elderly patients, especially those hospitalized with comorbidities, such as hypertension, diabetes, or coronary artery diseases. Because viral diseases may have atypical presentations in immunosuppressed patients, the course of the disease in the transplant patient population is unknown. Hence, the management of these patients with COVID-19 is an area of interest, and a unique approach is warranted. Here, we report the clinical features and our treatment approach for a kidney transplant patient with a diagnosis of COVID-19. We believe that screening protocols for SARS-Cov-2 should be re-evaluated in patients with solid-organ transplants.

Topics: Adult; Antiviral Agents; Betacoronavirus; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Disease Management; Female; Fever; Glucocorticoids; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lupus Nephritis; Oseltamivir; Pandemics; Pneumonia, Viral; Prednisone; SARS-CoV-2; Severity of Illness Index; Tacrolimus

The fatality of novel coronavirus disease 2019 (COVID-19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID-19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36-year-old man who underwent KT 3 years ago. He was diagnosed with COVID-19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID-19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug-to-drug interaction. The second case was developed in a 56-year-old man without any symptoms. He received a second KT from an ABO-incompatible donor 8 years ago. He was diagnosed with COVID-19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.

Topics: Adult; Antiviral Agents; Azithromycin; Betacoronavirus; Calcineurin Inhibitors; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Interactions; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tacrolimus; Transplant Recipients

Topics: Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Spain; Tacrolimus; Transplant Recipients

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Cross-Sectional Studies; Datasets as Topic; Drug Prescriptions; England; Geography; Graft Rejection; Health Services Accessibility; Humans; Infection Control; Organ Transplantation; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tacrolimus; Vulnerable Populations

Kidney transplant recipients have been reported at a particularly high risk of severe COVID-19 illness due to chronic immunosuppression and coexisting conditions. Yet, here we describe a remarkably mild case of COVID-19 in a 62-year-old female who had a kidney transplantation 10 years earlier due to autosomal dominant polycystic kidney disease. The patient was admitted for 1 day; immunosuppressive therapy with tacrolimus and low-dose prednisolone was continued; and the patient recovered successfully without the use of antiviral agents or oxygen therapy. The case demonstrates that kidney transplant recipients are not necessarily severely affected by COVID-19. Withdrawal of immunosuppressive therapy could be associated with poorer outcomes and should not be implemented thoughtlessly.

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Female; Glucocorticoids; Hospitalization; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Pandemics; Pneumonia, Viral; Prednisolone; SARS-CoV-2; Tacrolimus; Transplant Recipients; Treatment Outcome

Topics: Acute Kidney Injury; Adult; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Darunavir; Drug Interactions; Drug Monitoring; Humans; Hydroxychloroquine; Immunosuppressive Agents; Liver Transplantation; Male; Pandemics; Pneumonia, Viral; Prednisone; Risk Adjustment; Ritonavir; SARS-CoV-2; Tacrolimus; Transplant Recipients; Treatment Outcome

Topics: Anti-Infective Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Monitoring, Immunologic; Mycophenolic Acid; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Prednisolone; SARS-CoV-2; Tacrolimus; Treatment Outcome

Recent research has shown that Coronavirus (CoV) replication depends on active immunophilin pathways. Here we demonstrate that the drug FK506 (Tacrolimus) inhibited strongly the growth of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E at low, non-cytotoxic concentrations in cell culture. As shown by plaque titration, qPCR, Luciferase- and green fluorescent protein (GFP) reporter gene expression, replication was diminished by several orders of magnitude. Knockdown of the cellular FK506-binding proteins FKBP1A and FKBP1B in CaCo2 cells prevented replication of HCoV-NL63, suggesting the requirement of these members of the immunophilin family for virus growth.

Topics: Caco-2 Cells; Coronavirus 229E, Human; Coronavirus Infections; Coronavirus NL63, Human; Humans; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Tacrolimus; Tacrolimus Binding Proteins; Virus Replication