COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?

Willicombe, Michelle; Thomas, David; McAdoo, Stephen P.

doi:10.1681/asn.2020030348

Cited by 93 publications

(109 citation statements)

References 17 publications

(29 reference statements)

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“…In contrast, Cyclosporin A is an approved immunosuppressant that we found is also antiviral at concentrations achieved in vivo (110). Therefore, it may be useful to implement clinical trials using Cyclosporin A as an immunosuppressant as it would potentially ameliorate symptoms by two mechanisms (111).…”

Section: Discussionmentioning

confidence: 84%

Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2

Dittmar

Lee

Whig

et al. 2020

Preprint

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There are an urgent need for antivirals to treat the newly emerged SARS-CoV-2. To identify new candidates we screened a repurposing library of ~3,000 drugs. Screening in Vero cells found few antivirals, while screening in human Huh7.5 cells validated 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we found that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH-independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. These antivirals reveal essential host targets and have the potential for rapid clinical implementation.

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Section: Discussionmentioning

confidence: 84%

Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2

Dittmar

Lee

Whig

et al. 2020

Preprint

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“…It has been hypothesized that CNIs can lead to immune modulation against the virus and thus may be beneficial in reducing the cytokine release storm that is frequently seen with COVID-19. 61 Thus, cautious reduction rather than complete elimination of immunosuppression may avoid precipitation of severe complications like ARDS. This, however, remains to be proven in clinical studies.…”

Section: Managementmentioning

confidence: 99%

COVID-19 in Kidney Transplantation: Epidemiology, Management Considerations, and the Impact on Kidney Transplant Practice

Kataria

Yakubu

Winstead

et al. 2020

Transplantation Direct

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The novel severe acute respiratory syndrome coronavirus 2 was identified in the late 2019 as the cause of coronavirus disease 2019 (COVID-19), an acute respiratory viral illness. Patients with chronic underlying conditions may have an increased risk of morbidity and mortality from COVID-19. Kidney transplant recipients may be at a uniquely increased risk of serious complications from COVID-19 as compared to the general population because of a chronically immunosuppressed state and a high prevalence of comorbidities like diabetes, heart disease, and lung disease. Early data suggest that the mortality of patients on dialysis may be comparable to those with kidney transplants, although more research is needed. This concise review aims to describe the epidemiology of COVID-19 in kidney transplant recipients, manifestations, appropriate management, and clinical outcomes based on the available literature. Current evidence on many of the specific antiviral measures against COVID-19 has not shown a clear-cut benefit in smaller studies and the results of several ongoing larger clinical trials are awaited. In addition, we also highlight the impact of COVID-19 on kidney transplant center practice and volumes; potential living or deceased donors, recipients; and induction immunosuppression and surgical strategies.

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“…Immunosuppressive drugs may prolong viral shedding, have beneficial anti-inflammatory effects, or even have anti-viral properties [ 70 ]. Little is known about the exact role of cyclophilin in coronavirus replication, but it has been reported that cyclosporine, which also binds cyclophilin, may inhibit the replication of coronaviruses at noncytotoxic concentrations [ 71 , 72 ]. In vitro, tacrolimus inhibited the replication of SARS-CoV, suggesting the requirement of FK506-binding proteins for virus growth [ 73 ].…”

Section: Outpatient Management For Transplant Recipientsmentioning

confidence: 99%

General Approach to the Clinical Care of Solid Organ Transplant Recipients with COVID-19 Infection

2020

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Purpose of Review Insufficient knowledge about COVID-19 and the potential risks of COVID-19 are limiting organ transplantation in wait-listed candidates and deferring essential health care in solid organ transplant recipients. In this review, we expand the understanding and present an overview of the optimized management of COVID-19 in solid organ transplant recipients. Recent Findings Transplant recipients are at an increased risk of severe COVID-19. The unique characteristics of transplant recipients can make it more difficult to identify COVID-19 . Based on the COVID-19 data to date and our experience, we present testing, management, and prevention methods for COVID-19. Comprehensive diagnostic tests should be performed to determine disease severity, phase of illness, and identify other comorbidities in transplant recipients diagnosed with COVID-19. Outpatients should receive education for preventative measures and optimal health care delivery minimizing potential infectious exposures. Multidisciplinary interventions should be provided to hospitalized transplant recipients for COVID-19 because of the complexity of caring for transplant recipients. Summary Transplant recipients should strictly adhere to infection prevention measures. Understanding of the transplant specific pathophysiology and development of effective treatment strategies for COVID-19 should be prioritized.

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COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?

Cited by 93 publications

References 17 publications

Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2

Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2

COVID-19 in Kidney Transplantation: Epidemiology, Management Considerations, and the Impact on Kidney Transplant Practice

General Approach to the Clinical Care of Solid Organ Transplant Recipients with COVID-19 Infection

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