Metformin shows promising antiviral activity against SARS-CoV-2 COVID19 Treatment MetforminResearch ViralLoadReduction OutpatientTrial SARSCoV2 Ivermectin Fluvoxamine AntiviralTherapy MedicalResearch PublicHealth medrxivpreprint
By Neha MathurJun 12 2023Reviewed by Benedette Cuffari, M.Sc. In a recent article posted to the medRxiv* preprint server, researchers present the results of severe acute respiratory coronavirus 2 load quantification obtained during the COVID-OUT clinical trial.
In vitro experiments, consistent with model predictions, have shown that metformin, a widely available and inexpensive oral medication for diabetes, exhibits antiviral activity of RNA viruses, including SARS-CoV-2. Moreover, metformin appears to reduce the growth of SARS-CoV-2 and improve host cell viability, thus emerging as an ideal drug candidate for drug repurposing and combating COVID-19.
As a quadruple-blinded trial, study participants, investigators, and laboratory personnel processing the trial samples were blinded to study drug allocation. COVID-19 was also decentralized to prevent the person-to-person spread of SARS-CoV-2. Ivermectin or fluvoxamine exhibited no antiviral activity by days five or 10. Comparatively, metformin reduced the average SARS-CoV-2 viral load by -0.56 log10 copies/ml more than the placebo across all follow-up evaluations of day one samples.
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Systems genetics identifies miRNA-mediated regulation of host response in COVID-19 - Human GenomicsBackground Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. Results We combined multi-omics profiling—genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms—with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. Conclusions This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.
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