Pharmacogenomics of COVID-19 therapies

Takuto Takahashi; Jasmine A Luzum; Melanie R Nicol; Pamala A Jacobson

doi:10.1038/s41525-020-00143-y

Pharmacogenomics of COVID-19 therapies

NPJ Genom Med. 2020 Aug 18:5:35. doi: 10.1038/s41525-020-00143-y. eCollection 2020.

Authors

Takuto Takahashi^{1

2}, Jasmine A Luzum³, Melanie R Nicol¹, Pamala A Jacobson¹

Affiliations

¹ Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota, Minneapolis, MN USA.
² Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN USA.
³ Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI USA.

Abstract

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.

Keywords: Genetic markers; Viral infection.

Publication types

Review

Abstract

Publication types

Grants and funding