Remdesivir Administration in COVID-19 Patients With Renal Impairment: A Systematic Review.

BACKGROUND: Remdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time to clinical improvement of COVID-19 and mortality benefits in patients receiving RDV. The patients with renal disease were excluded from large clinical trials of RDV, and the probable nephrotoxicity of the drug, its metabolites, and the vehicle (sulfobutylether-ß-cyclodextrin) have led to the recommendation against using RDV in patients with an estimated glomerular filtration rate of <30 mL/min. AREAS OF UNCERTAINTY: This systematic review aimed to collect data about the necessity and safety administration of RDV in the setting of renal impairment. DATA SOURCES: Search through databases including MEDLINE, ScienceDirect, Cochrane Library, and PubMed was performed. The studies were carried out in adults and enrolled patients with different types of renal impairment (ie, acute kidney injury, chronic kidney disease, kidney transplant, and renal replacement therapy) were included. Eligible studies were assessed, and required data were extracted. RESULTS: Twenty-two cross-sectional studies, cohorts, case reports, and case series were included in this review. The mortality rate was between 7.3% and 50%, and various severity of COVID-19 was included in the studies. None of them reported an increase in adverse effects attributed to RDV administration. A decrease in inflammatory mediators and other benefits were obvious. CONCLUSIONS: Although the manufacturer's labeling does not recommend RDV administration in patients with severe renal impairment, it seems that nephrotoxicity is less concerning in the population of these patients. Moreover, RDV may be helpful in acute kidney injury induced by the viral invasion of COVID-19. To the best of our knowledge, this is the first systematic review of the use of RDV in kidney failure. Larger, well-designed, and pharmacokinetic studies are required to have a safe and logical recommendation about the use of RDV in patients with renal disorders.

Melatonin as adjunctive therapy in patients admitted to the Covid-19.

Objective: Coronavirus has disrupted the natural order of the world since September 2019 with no specific medication. The beneficial effects of melatonin on sepsis and viral influenza were demonstrated previously, but its effects on covid-19, especially COVID -19 ICU, is unclear. Therefore, our aim was to determine the effects of melatonin in COVID-19 ICU patients. Methods: This is a retrospective cohort study in which the records of patients admitted to COVID -19 ICU of (XXX) during March to June 2020 were reviewed. According to inclusion criteria, patients who received 15 mg of melatonin daily were called MRG and the rest were called NMRG. Results: Thirty-one patients were included and analyzed, of which twelve patients were in MRG. Demographic and clinical characteristics, and laboratory data were similar between two groups at ICU admission. Melatonin had no significant effect on ICU duration, CRP and ESR, also the trend of changes was in favor of melatonin. Nevertheless, melatonin significantly reduced the NLR (OR = -9.81, p = 0.003), and also declined mortality marginally (p = 0.09). Melatonin was well tolerated with no major adverse effects, moreover the thrombocytopenia occurrence was significantly lower in MRG (p = 0.005). In MRG, survival increased and mortality risk decreased, although the difference between groups wasn't significant (p = 0.37), which might be related to the small sample-size. Conclusion: Our study showed that melatonin is unlikely to reduce mortality among COVID19 patients and with no significant effect on disease-specific biochemical parameters.

Pentoxifylline effects on hospitalized patients with COVID19: A randomized, double-blind clinical trial.

Pentoxifylline (PTX) has broad-spectrum properties such as anti-inflammatory, anticoagulant, and antiviral effects. The aim of this study was to evaluate the efficacy and safety of PTX in hospitalized patients with COVID-19. This double-blind, placebo-controlled randomized clinical trial was conducted on hospitalized patients with COVID-19. The recruited patients were randomly (1:1) assigned to the PTX group and the placebo group. The intervention group received PTX capsules at a dose of 400 mg three times a day for 10 days along with the national regimen, including interferon plus lopinavir/ritonavir and hydroxychloroquine. The primary outcome was the improvement of clinical scores. The secondary outcomes, on the other hand, were improvement in inflammatory and oxidative stress factors and hospital complications. From a total of 102 patients who met the inclusion criteria, 72 individuals completed the study and were analyzed. No significant differences were shown in demographics and baseline clinical characteristics. Clinical scores was not significant between the two groups (P = 0.31 and 0.07 for day 5 and 11, respectively). Although the mean serum levels of interleukin-6 (IL-6) and glutathione changed significantly after 5 days in the PTX group (P = 0.03 and p = 0.04), ICU admission, intubation, and hospital stay did not differ between the two groups. The results of our study did not show any superiority of PTX over placebo in improving the clinical outcomes of patients with COVID-19. Although PTX had a beneficial effect on IL-6 and showed an acceptable safety profile, it did not offer any clinical benefit for COVID-19 complications.