ABSTRACT
Kidney transplant recipients (KTRs) are at increased risk for a more severe course of COVID-19, due to their pre-existing comorbidity and immunosuppression. Consensus protocols recommend lowering immunosuppression in KTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the optimal combination remains unclear. Calcineurin inhibitors (CNIs) are cornerstone immunosuppressants used in KTRs and some have been reported to possess antiviral activity against RNA viruses, including coronaviruses. Here, we evaluated the effect of the CNIs tacrolimus, cyclosporin A, and voclosporin (VCS), as well as other immunosuppressants, on SARS-CoV-2 replication in cell-based assays. Unexpected, loss of compound due to plastic binding and interference of excipients in pharmaceutical formulations (false-positive results) complicated the determination of EC50 values of cyclophilin-dependent CNI's in our antiviral assays. Some issues could be circumvented by using exclusively glass lab ware with pure compounds. In these experiments, VCS reduced viral progeny yields in human Calu-3 cells at low micromolar concentrations and did so more effectively than cyclosporin A, tacrolimus or other immunosuppressants. Although, we cannot recommend a particular immunosuppressive regimen in KTRs with COVID-19, our data suggest a potential benefit of cyclophilin-dependent CNIs, in particular VCS in reducing viral progeny, which warrants further clinical evaluation in SARS-CoV-2-infected KTRs.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Calcineurin Inhibitors/pharmacology , Calcineurin Inhibitors/therapeutic use , Cell Culture Techniques , Cyclophilins , Cyclosporine/pharmacology , Humans , Immunosuppressive Agents/adverse effects , Tacrolimus/pharmacologyABSTRACT
Purpose>This case study aims to explore the appropriateness of an adaptive riding program for persons living with dementia through examining family members’ (care partners) reported outcomes.Design/methodology/approach>Using convenience sampling, persons living with dementia and their care partners were recruited in Northern Colorado;after meeting inclusion criteria, they were invited to participate in the adaptive riding program. The program occurred for weekly, hour-long sessions for eight weeks. Field notes were collected during each session, and semi-structured interviews were conducted with five care partners after the program and analyzed by using theoretical thematic analysis.Findings>Care partners found the adaptive riding program appropriate. Reported outcomes comprised three themes: well-being, meaning through social connections and function in daily life and aligned with the positive emotions, engagement, relationships, meaning, accomplishment (PERMA) theory of well-being.Originality/value>To the best of the authors’ knowledge, this is the first study to explore the appropriateness of an adaptive riding program for persons living with dementia and their care partners who broadened understandings of the emotional, social and physical benefits. Findings support the inclusion of care partners in adaptive riding and may inform health-care providers’ recommendations for such programs.