Drug-related Problems in Solid-Organ Transplant Recipients Hospitalized for COVID-19: An Experience of a Referral Tertiary Center in Iran.

Background: Transplanted patients receiving immunosuppressive agents are at a higher risk of Coronavirus-disease-2019 (COVID-19), and their polypharmacy state makes the choice of treatment challenging. This study aimed to assess the drug-related problems (DRP) and clinical pharmacists' interventions to manage transplanted patients and candidates for transplantation with COVID-19. Methods: This cross-sectional study was conducted in the COVID-19 intensive care unit of Shiraz Organ Transplantation Center (Iran), from March 2020 to April 2021. Patients were admitted to the COVID-19 intensive care unit based on clinical symptoms or positive polymerase chain reaction (PCR) tests. The clinical pharmacist reviewed all medications and physicians' orders on a daily basis and evaluated DRPs in accordance with the pharmaceutical care network of Europe (PCNE) classification (V 8.01). The treatment team was informed of the DRPs, and the acceptance or rejection of the intervention was also documented. Data were analyzed using SPSS (Version 25.0). In order to determine the proportion and determinants of drug-related problems, descriptive statistics and logistic regression were applied, respectively. Results: A clinical pharmacist reviewed 631 individuals with 11770 medication orders, and 639 DRPs were found in 69% of them with an average of 1.01±1 per patient. The most commonly reported DRPs were treatment efficacy issues followed by adverse drug reactions (ADRs). A total of 982 interventions were provided at prescriber, patient, and drug levels, of which 801 were accepted, and 659 (82.27%) were fully implemented. Conclusion: There have been considerable drug-related issues in managing transplanted patients with COVID-19. DRPs are more common in people with polypharmacy, more than three comorbidities, and hydroxychloroquine regimens.

Inflammation: A bridge between diabetes and COVID-19, and possible management with sitagliptin.

Patients with SARS-CoV-2 infections experience lymphopenia and inflammatory cytokine storms in the severe stage of the disease, leading to multi-organ damage. The exact pattern of immune system changes and their condition during the disease process is unclear. The available knowledge has indicated that the NF-kappa-B pathway, which is induced by several mediators, has a significant role in cytokine storm through the various mechanisms. Therefore, identifying the state of the immune cells and the dominant mechanisms for the production of cytokines incorporated in the cytokine storm can be a critical step in the therapeutic approach. On the other hand, some studies identified a higher risk for diabetic patients. Diabetes mellitus exhibits a close association with inflammation and increases the chance of developing COVID-19. Patients with diabetes mellitus have shown to have more virus entry, impaired immunity response, less viral elimination, and dysregulated inflammatory cytokines. The parallel analysis of COVID-19 and diabetes mellitus pathogenesis has proposed that the control of the inflammation through the interfering with the critical points of major signaling pathways may provide the new therapeutic approaches. In recent years, the role of Dipeptidyl Peptidase 4 (DPP4) in chronic inflammation has been proved. Numerous immune cells express the DPP4 protein. DPP4 regulates antibody production, cytokine secretion, and immunoglobulin class switching. DPP4 inhibitors like sitagliptin reduce inflammation intensity in different states. Following the accumulating data, we hypothesize that sitagliptin might reduce COVID-19 severity. Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients. It reduces the inflammation mostly by affecting on NF-kappa-B signaling pathway. Under the fact that inflammatory mediators are active in individuals with COVID-19, blocking the predominant pathway could be helpful.