Severity Tomographic Score as a Predictor of Mortality in Patients With Covid-19 Pneumonia From a Third-level Hospital in Peru (preprint)

Objective: Determine whether the tomographic characteristics of patients with COVID-19 pneumonia at the hospital admission and the initial tomographic severity score (TSS) as well as some laboratory tests or clinical characteristics predict mortality. Methods: Retrospective analytical study that included patients with a clinical diagnosis of SARSCoV2 virus infection, performed by reverse transcriptase polymerase chain reaction (RT-PCR), serologic reactive test (IgM/IgG) and/or thoracic computed tomography (CT). Patients were divided into two groups: recovered and deceased. Two radiologists (blind evaluators) described the tomographic findings. TSS, clinical and laboratory parameters in relation to mortality were analyzed. Mortality predictions were made by binary logistic regression. Results: Hypertension was the most frequent associated disease, the most common clinical presentation included cough, discomfort, fever, and dyspnea. The ground glass opacity pattern was the most frequent, followed by consolidation and distortion of the architecture; however, they were not associated with higher mortality. The pattern of pleural effusion and bronchial dilation showed a significant difference from mortality (p <0.05). The binary logistic regression model showed that a moderate and high TSS (≥ 8), as well as a higher degree of lymphopenia, history of asthma and age were associated with an increased risk of death (p< 0.05). Conclusions: TSS is useful in the initial and comprehensive diagnostic evaluation of COVID-19 pneumonia, in conjunction with markers such as lymphopenia that can predict a poor short-term outcome. A high TSS score is a predictor of mortality.

A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019 (preprint)

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro.Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396.Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m2, and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses.Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.