Abstract
AimsCoronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Drug therapy is one of the major treatments, but contradictory results of clinical trials have been reported among different individuals. Furthermore, comprehensive analysis of personalized pharmacotherapy is still lacking. In this study, analyses were performed on 47 well-characterized COVID-19 drugs used in the personalized treatment of COVID-19.MethodsClinical trials with published results of drugs use for COVID-19 treatment were collected to evaluate drug efficacy. Drug-to-Drug Interactions (DDIs) were summarized and classified. Functional variations in actionable pharmacogenes were collected and systematically analysed. “Gene Score” and “Drug Score” were defined and calculated to systematically analyse ethnicity-based genetic differences, which are important for the safer use of COVID-19 drugs.ResultsOur results indicated that four antiviral agents (ritonavir, darunavir, daclatasvir and sofosbuvir) and three immune regulators (budesonide, colchicine and prednisone) as well as heparin and enalapril could generate the highest number of DDIs with common concomitantly utilized drugs. Eight drugs (ritonavir, daclatasvir, sofosbuvir, ribavirin, interferon alpha-2b, chloroquine, hydroxychloroquine (HCQ) and ceftriaxone had actionable pharmacogenomics (PGx) biomarkers among all ethnic groups. Fourteen drugs (ritonavir, daclatasvir, prednisone, dexamethasone, ribavirin, HCQ, ceftriaxone, zinc, interferon beta-1a, remdesivir, levofloxacin, lopinavir, human immunoglobulin G and losartan) showed significantly different pharmacogenomic characteristics in relation to the ethnic origin of the patient.ConclusionWe recommend that particularly for patients with comorbidities to avoid serious DDIs, the predictive, preventive, and personalized medicine (PPPM, 3 PM) strategies have to be applied for COVID-19 treatment, and genetic tests should be performed for drugs with actionable pharmacogenes, especially in some ethnic groups with a higher frequency of functional variations, as our analysis showed. We also suggest that drugs associated with higher ethnic genetic differences should be given priority in future pharmacogenetic studies for COVID-19 management. To facilitate translation of our results into clinical practice, an approach conform with PPPM/3 PM principles was suggested. In summary, the proposed PPPM/3 PM attitude should be obligatory considered for the overall COVID-19 management.
Highlights
The results presented below we are very important for practical application of the principles of predictive, preventive and personalized medicine in the clinical practice of COVID-19 management
We focused on three aspects including Drug-to-Drug Interactions (DDI), variations in pharmacogenes and the differences in drug utility arising from the ethnic differences
We recommended that antiviral agents, immune regulators, heparin and enalapril which could generate the most DDIs with commonly concomitantly utilized drugs should be under higher supervision to avoid potential DDIs
Summary
2020, the World Health Organization (WHO) reported a new disease caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 and declared a Public Health Emergency of International Concern [1,2,3,4]. A large number of patients have been infected and died due to this disease The virus is mainly spread by respiratory droplets. Millions of COVID19 cases could progress rapidly to acute respiratory distress syndrome (ARDS), shock, multiple organ failure and even death [6,7,8]. A large number of patients needed to be appropriately treated without delay in this situation
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