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BACKGROUNDThe effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir, and of their combined use in hospitalized patients with coronavirus disease 2019 (Covid-19) pneumonia is unclear. METHODSIn each hospital, hospitalized adults with Covid-19 pneumonia, were randomly assigned, in a 1:1 ratio, to receive: a) standard of care; or b) emtricitabine/tenofovir; or c) colchicine + rosuvastatin; or d) emtricitabine/tenofovir + colchicine + rosuvastatin. The primary outcome was all-cause mortality within the first 28 days after randomization. Severe adverse events (SAE) were those with a high probability of being treatment-related. RESULTS633 patients were randomized in 6 hospitals in Bogota, Colombia. Overall, 98% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death through day 28 was 10.7% in the emtricitabine/tenofovir + colchicine + rosuvastatin arm, 14.4% in the colchicine + rosuvastatin arm, 13.8% in the emtricitabine/tenofovir arm, and 17.4% in the standard of care arm, with adjusted risk differences (aRD) against the standard treatment of -0.07 (95% confidence interval [CI], -0.17 to 0.04), aRD -0.03 (95%CI: -0.11 to 0.05) and aRD: -0.05 (95%CI: -0.15 to 0.05), respectively. Need for invasive mechanical ventilation was lower in the emtricitabine/tenofovir + colchicine + rosuvastatin arm compared to the standard treatment arm, aRD: -0.06 (95%CI: -0.11 to -0,01), but no differences were found between the other comparisons. SAE occurred in 3 patients distributed in the 3 treatment arms. CONCLUSIONSAmong patients hospitalized with moderate and severe SARS Covid-19, the use of the emtricitabine/tenofovir + colchicine + rosuvastatin combination emerges as a treatment alternative. ClinicalTrials.gov number: NCT04359095
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BackgroundThe unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and FindingsWe develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. ConclusionsThere is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.
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Background@#Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E. @*Methods@#We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression. @*Results@#Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression. @*Conclusions@#In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.
