September 3, 2020
Dr. Jasmine Luzum
The goal of Dr. Luzum’s research is to use precision medicine, particularly genetics, to improve cardiovascular outcomes from medications. Adverse cardiac outcomes from drugs used to treat COVID-19 have recently been a major concern.

The COVID-19 pandemic continues to impact global health and safety. Numerous drugs are under expedited investigations, without well-established safety or efficacy data. Jasmine Luzum, PharmD, PhD, BCPS, assistant professor of clinical pharmacy, has published a review of pharmacogenomics for COVID-19 therapies in a Nature journal.

The goal of Dr. Luzum’s research is to use precision medicine, particularly genetics, to improve cardiovascular outcomes from medications. Adverse cardiac outcomes from drugs used to treat COVID-19 have recently been a major concern. 

“Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety,” explains Dr. Luzum. “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.”

Dr. Luzum and collaborators 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). They 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).

The team describes in the paper 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.

“Although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies,” notes Dr. Luzum. “Clinical studies in COVID-19 patients are warranted to assess potential roles of these markers.”