Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Abstract

The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients' outcomes with this complex disease; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. We aimed to describe the pharmacogenetic variants reported for drugs used for COVID-19 treatment (remdesivir, oseltamivir, lopinavir, ritonavir, azithromycin, chloroquine, hydroxychloroquine, ivermectin, and dexamethasone). In addition, other factors relevant to the design of pharmacogenetic studies were mentioned. Variants in CYP3A4, CYP3A5, CYP2C8, CY2D6, ABCB1, ABCC2, and SLCO1B1, among other variants, could be included in pharmacogenetic studies of COVID-19 treatment. Besides, nongenetic factors such as drug-drug interactions and inflammation should be considered in the search for personalized therapy of COVID-19.

Keywords: ABCB1; COVID-19; CYP2D6; CYP3A4; NR1I2; pharmacogenetics.

Figure 1

Pharmacogenetics of COVID-19 treatment. The identification of pharmacogenetic biomarkers of relevance in drugs used for COVID-19 treatment and nongenetic factors could provide the information to make dosages adjustments or the selection of the optimal treatment for the patient. Achieving a personalized therapy would assure drug plasma concentrations within the therapeutic range, leading to several advantages in the disease’s clinical outcome. Created with BioRender.com, accessed on 19 February 2021.

Figure 2

Schematic summary of drug-metabolizing enzymes and transporters of drugs used for the COVID-19 treatment. A yellow-star has been added in drugs with relevant pharmacogenetic knowledge considering if the enzyme or transporter meets the following: (1) it is considered as a Pharmacogenomic Biomarker according to the FDA (https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling, accessed on 19 February 2021); (2) it is included as pharmacogene variant in Pharmgkb (https://www.pharmgkb.org/, accessed on 19 February 2021); and/or (3) it has been associated with the pharmacokinetics and/or pharmacodynamics of the corresponding drug in a scientific report. AZT, azithromycin; CHL, chloroquine; DEX, dexamethasone; HCL, hydroxychloroquine; IVE, ivermectin; LOP, lopinavir; OSE, oseltamivir; REM, remdesivir; RIT, ritonavir. Created with BioRender.com, accessed on 19 February 2021.