Remdesivir and COVID-19

Release time:2020-10-03

Impact Factor:202.731

DOI number:10.1016/S0140-6736(20)32019-5

Affiliation of Author(s):中南大学湘雅医院

Teaching and Research Group:临床药理研究所

Journal:Lancet

Key Words:Remdesivir,COVID-19, SARS-COV-2

Abstract:In a Chinese clinical trial by Yeming Wang and colleagues,1 remdesivird did not show significant benefits for patients with severe COVID-19. Shortly after their study was published, remdesivir was authorised in the USA by the US Food & Drug Administration2 and approved in Japan3 for patients with severe COVID-19 on the basis of preliminary phase 3 trial results.4 We find it puzzling that the discrepancy of results between China and the USA is merely justified by different study designs. Genetic factors can influence drugs' efficacy and toxicity. Therefore, it is reasonable to seek answers from the genetic backgrounds of patients with COVID-19 and of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China and the USA. From the GnomAD database, we collected: 9977 genomes from east Asia that represented Chinese people; and 64 603 genomes from Europeans, 17 720 from Latinx, and 12 487 from African Americans, which represented the three majority ethnicities in the USA.5 Genetic diversity was found in seven pharmacogenes that mainly related to pharmacokinetics and pharmacodynamics of remdesivir.6 Notably, the mutation frequency of CYP2D6 (rs1065852) in east Asia (57·7%) was much greater than that of the American ethnicities (12·3–21·7%), whereas the mutation frequency of SLCO1B3 (rs60140950) showed the opposite result (appendix). Meanwhile, we also collected 432 SARS-CoV-2 samples from China and 2754 SARS-CoV-2 samples from the USA using an online database.7 The frequency of potential functional variations such as p.P4715L (c.14144C>T) in polyprotein 1ab, which is the target of remdesivir, were largely different in the genomes from the USA (63·0%) and China (11·2%). These variations could generate the efficacy discrepancy of remdesivir among these clinical trials. Similar to remdesivir, ethnic diversity was also found in pharmacogenes related to other drugs, such as chloroquine, in COVID-19 treatment. In summary, pharmacogenomic studies for COVID-19 therapy seem to be needed urgently.

Co-author:Guo CX, Zhan Y, Ouyang QY, Cui JJ

First Author:Wang LY

Indexed by:Other

Correspondence Author:Yin JY

Discipline:Medicine

First-Level Discipline:Pharmaceutical Science

Volume:396

Issue:10256

Page Number:953–954

ISSN No.:1474-547X

Translation or Not:no

Date of Publication:2020-10-03

Included Journals:SCI