Pharmacogenetic Markers of Favipiravir Safety in COVID-19 Treatment

Abstract

The aim of the study was to evaluate the associations of different variants of AOX1 and CYP1A2 genes with safety parameters of favipiravir therapy in patients with COVID-19. Material and Methods. The study included 86 patients hospitalized at Moscow Clinical Hospital No. 15 with a COVID-19 diagnosis who received favipiravir as etiotropic therapy. Frequency of adverse reactions (bradycardia, dyspeptic disorders, increased transaminase levels) and various laboratory parameters (levels of ALT, AST, leukocytes) were compared between the carriers of «wild» and polymorphic variants of the genes studied after administration of the drug. The dynamics of these indicators before and after the therapy depending on the carriage of the variants of the genes studied were also compared. Results. There was no significant difference in the frequency of ad- verse reactions and laboratory parameters between the carriers of various variants of the studied genes. Haplotype analysis of the combination of different gene variants also did not reveal associations with therapy safety parameters. Upon the comparison of the parameters before and after treatment, an increase in the level of AST was noted in carriers of the AA genotype for both studied loci of the AOX1 gene (P=0.018 и P=0.009). At the same time, the level of AST increased in carriers of polymorphic variants of the CYP1A2*F1 gene (P=0.024). Leukocyte number increase was noted in carriers of polymorphic variants of AOX1 (rs10931910) (P=0.044), as well as «wild» genotypes AOX1 (rs55754655) (P=0.002) and CYP1A2*F1 (P=0.05). Conclusion. The associations of carriers of different AOX1 and CYP1A2 gene variants on the dynamics of AST and leukocytes in patients with COVID-19 after favipiravir therapy were revealed.

Keywords

• favipiravir
• pharmacogenetics
• safety
• polymorphisms
• personalization
• covid-19
• aox1
• cyp1a2
• rs55754655
• rs10931910
• rs762551