A new global pandemic of coronavirus disease 2019 (COVID-19) has resulted in high mortality and morbidity. Currently numerous drugs are under expedited investigations without well-established safety or efficacy data. Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety. In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We searched PubMed, reviewed the Pharmacogenomics Knowledgebase (PharmGKB ® ) website, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the U.S. Food and Drug Administration (FDA) pharmacogenomics information in the product labeling, and the FDA pharmacogenomics association table. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). We also identified other variants, that are associated with adverse effects, most notable in hydroxychloroquine/chloroquine (G6PD; hemolysis), ribavirin (ITPA; hemolysis), and interferon β -1b (IRF6; liver toxicity). We also describe the complexity of the risk for QT prolongation in this setting because of additive effects of combining more than one QT-prolonging drug (i.e., hydroxychloroquine/chloroquine and azithromycin), increased concentrations of the drugs due to genetic variants, along with the risk of also combining therapy with potent inhibitors. In conclusion, although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies. Clinical studies in COVID-19 patients are deemed warranted to assess potential roles of these markers.
【저자키워드】 viral infection, Genetic markers, 【초록키워드】 COVID-19, coronavirus disease, Efficacy, Baricitinib, Corticosteroids, therapy, Chloroquine, Hydroxychloroquine, Tocilizumab, variant, interferon, Remdesivir, Favipiravir, risk, Toxicity, pharmacogenetics, drug, FDA, ribavirin, inhibitors, global pandemic, QT prolongation, adverse effects, Hemolysis, clinical, morbidity, CYP2D6, ruxolitinib, Efficacy and safety, genetic variants, information, pharmacogenomics, liver, Therapies, association, food, Evidence, Concentration, Interferon beta-1b, COVID-19 patient, website, other variants, high mortality, ABCC2, CYP2C8, SLCO1B1, labeling, hydroxychloroquine/chloroquine, Effect, Alter, genetic marker, searched, notable, SLC28A2, SLC29A1, SLCO1A2, 【제목키워드】 COVID-19, therapy, pharmacogenomics,