RESUMO
We investigated Favipiravir (FPV) efficacy in mild cases of COVID-19 without pneumonia and its effects towards viral clearance, clinical condition, and risk of COVID-19 pneumonia development. PCR-confirmed SARS-CoV-2-infected patients without pneumonia were enrolled (2:1) within 10 days of symptomatic onset into FPV and control arms. The former received 1800 mg FPV twice-daily (BID) on Day 1 and 800 mg BID 5-14 days thereafter until negative viral detection, while the latter received supportive care only. The primary endpoint was time to clinical improvement, which was defined by a reduced National Early Warning Score (NEWS) or score of [≤]1. 62 patients (41 female) comprised the FPV arm (median age: 32 years, median BMI: 22 kg/m{superscript 2}) and 31 patients (19 female) comprised the control arm (median age: 28 years, median BMI: 22 kg/m{superscript 2}. The median time to sustained clinical improvement by NEWS was 2 vs 14 days for FPV and control arms respectively (adjusted hazard ratio (aHR) of 2.77, 95% CI 1.57-4.88, P <0.001). The FPV arm also had significantly higher likelihoods of clinical improvement within 14 days after enrolment by NEWS (79% vs 32% respectively, P <0.001), particularly female patients (aOR 6.35, 95% CI 1.49-27.07, P <0.001). 8 (12.9%) and 7 (22.6%) patients in FPV and control arms developed mild pneumonia at a median (range) 6.5 (1-13) and 7 (1-13) days after treatment, respectively (P = 0.316); all recovered well without complications. We can conclude that early treatment of FPV in symptomatic COVID-19 patients without pneumonia was associated with faster clinical improvement.
RESUMO
Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic??hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 microg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.
