# The therapeutic landscape for COVID-19 and post-COVID-19 medications from genetic profiling of the Vietnamese population and a predictive model of drug-drug interaction for comorbid COVID-19 patients

## TL;DR

This study explores how genetic differences in the Vietnamese population affect responses to and interactions between drugs used for treating and managing post-COVID-19 conditions.

## Contribution

The paper introduces a pharmacogenomic analysis of Vietnamese individuals for both current and post-COVID-19 therapies and a predictive model for drug interactions.

## Key findings

- Vietnamese individuals commonly carry genetic variants affecting responses to tolicizumab, ritonavir, and antithrombotic drugs.
- Drugs for mental health show the most clinical annotated variants in the Vietnamese population for post-COVID-19 treatment.
- Comorbid patients face increased drug-drug interaction risks during and after COVID-19 due to multiple potential interactions.

## Abstract

Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.