Clinical limitations
comorbidity
PATHOLOGY, SARS-COV-2 INFECTION, STILL
While our clinical results are highly encouraging, baseline differences between the groups and lack of randomization must be noted. Therefore, confounding and/or random error cannot be excluded. For instance, the higher comorbidity burden in the fenofibrate group may have conditioned a lower threshold for the initial hospital admission, with consequent favorable differences in outcomes relative to controls.In addition, it must be noted that the study controls were assigned from neighboring clinical centers serving the same diverse and mixed ethnic population, as clinical outcomes of non-consenting patients at the Barzilai Medical Center were significantly worse than the treatment group as these patients often refused or had difficulties in adhering to treatment. Thus, the best control that replicated the clinical characteristics of the patients and course of treatment, were patients that were qualified for the study but were not included simply because they were in another local hospital. Standard of care during this time period was identical for all clinical centers in Israel.Our work demonstrates the importance of weaving primary human cells, with clinical samples, and observational data for the rapid clinical translation of new metabolic interventions. Additional work is needed to confirm the specific activation of biochemical pathways and validate our findings in pathology samples. Still, this mechanistic understanding allowed us to design an ad hoc preliminary prospective clinical study and showed significant differences from the control group despite the small number of patients.Our work charts the metabolic response of human lung epithelium to SARS-CoV-2 infection. Our data suggest that the up-regulation of lipid oxidation might be an effective therapeutic target in the treatment of COVID-19. A definitive answer regarding the efficacy of fenofibrate for the treatment of COVID-19 will require the execution of large randomized controlled clinical trials with meaningful clinical outcomes. Two randomized placebo-controlled trials are ongoing, including a large international trial in the US, Mexico, Greece, and several South American countries (FERMIN trial; NCT04517396), and a clinical trial in Israel (FENOC trial; NCT04661930).