Pharmacogenomic Study of SARS-CoV-2 Treatments: Identifying Polymorphisms Associated with Treatment Response in COVID-19 Patients

<b>Background/Objectives</b>: The COVID-19 pandemic resulted in 675 million cases and 6.9 million deaths by 2022. Despite substantial declines in case fatalities following widespread vaccination campaigns, the threat of future coronavirus outbreaks remains a concern. Current treatments for COVID-19 have been repurposed from existing therapies for other infectious and non-infectious diseases. Emerging evidence suggests a role for genetic factors in both susceptibility to SARS-CoV-2 infection and response to treatment. However, comprehensive studies correlating clinical outcomes with genetic variants are lacking. The main aim of our study is the identification of host genetic biomarkers that predict the clinical outcome of COVID-19 pharmacological treatments. <b>Methods</b>: In this study, we present findings from GWAS and candidate gene and pathway enrichment analyses leveraging diverse patient samples from the Spanish Coalition to Unlock Research of Host Genetics on COVID-19 (SCOURGE), representing patients treated with immunomodulators (<i>n</i> = 849), corticoids (<i>n</i> = 2202), and the combined cohort of both treatments (<i>n</i> = 2487) who developed different outcomes. We assessed various phenotypes as indicators of treatment response, including survival at 90 days, admission to the intensive care unit (ICU), radiological affectation, and type of ventilation. <b>Results</b>: We identified significant polymorphisms in 16 genes from the GWAS and candidate gene studies (TLR1, TLR6, TLR10, CYP2C19, ACE2, UGT1A1, IL-1α, ZMAT3, TLR4, MIR924HG, IFNG-AS1, ABCG1, RBFOX1, ABCB11, TLR5, and ANK3) that may modulate the response to corticoid and immunomodulator therapies in COVID-19 patients. Enrichment analyses revealed overrepresentation of genes involved in the innate immune system, drug ADME, viral infection, and the programmed cell death pathways associated with the response phenotypes. <b>Conclusions</b>: Our study provides an initial framework for understanding the genetic determinants of treatment response in COVID-19 patients, offering insights that could inform precision medicine approaches for future epidemics.

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Journal
Biomedicines
Published
2025-02-21
DOI
https://doi.org/10.3390/biomedicines13030553
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Pharmacogenomic Study of SARS-CoV-2 Treatments: Identifying Polymorphisms Associated with Treatment Response in COVID-19 Patients

Gladys G. Olivera, Marta Cortón, Raquel Cruz, Marí­a José Herrero et al.
Biomedicines
COVID-19 Clinical Research Studies
article

Pharmacogenomic Study of SARS-CoV-2 Treatments: Identifying Polymorphisms Associated with Treatment Response in COVID-19 Patients

Gladys G. Olivera, Marta Cortón, Raquel Cruz, Marí­a José Herrero, Berta Almoguera, Rocio Ortı́z-López, Pablo Mínguez, Pablo Lapunzina, Maria Jesús Arranz, Rosario López‐Rodríguez, Anna Sangil, José A. Riancho, Natàlia Cullell, Esther Calbo, Olalla Maroñas, Carlos Flores, Estela Paz‐Artal, Miguel López de Heredia, Carmen Ayuso, Esther Mancebo, Encarna Guillén‐Navarro, Ángel Carracedo, Óscar Martínez-Nieto, María Barreda‐Sánchez, Beatriz Dietl, Alex Serra-Llovich, Luis Sendra, Almudena Gil-Rodríguez, David Dalmau, Elena Domínguez-Garrido, Lucía Boix-Palop, Saul Lira-Albarán, Sheila Recarey-Rama, Enrique G. Zucchet
article en

Abstract

<b>Background/Objectives</b>: The COVID-19 pandemic resulted in 675 million cases and 6.9 million deaths by 2022. Despite substantial declines in case fatalities following widespread vaccination campaigns, the threat of future coronavirus outbreaks remains a concern. Current treatments for COVID-19 have been repurposed from existing therapies for other infectious and non-infectious diseases. Emerging evidence suggests a role for genetic factors in both susceptibility to SARS-CoV-2 infection and response to treatment. However, comprehensive studies correlating clinical outcomes with genetic variants are lacking. The main aim of our study is the identification of host genetic biomarkers that predict the clinical outcome of COVID-19 pharmacological treatments. <b>Methods</b>: In this study, we present findings from GWAS and candidate gene and pathway enrichment analyses leveraging diverse patient samples from the Spanish Coalition to Unlock Research of Host Genetics on COVID-19 (SCOURGE), representing patients treated with immunomodulators (<i>n</i> = 849), corticoids (<i>n</i> = 2202), and the combined cohort of both treatments (<i>n</i> = 2487) who developed different outcomes. We assessed various phenotypes as indicators of treatment response, including survival at 90 days, admission to the intensive care unit (ICU), radiological affectation, and type of ventilation. <b>Results</b>: We identified significant polymorphisms in 16 genes from the GWAS and candidate gene studies (TLR1, TLR6, TLR10, CYP2C19, ACE2, UGT1A1, IL-1α, ZMAT3, TLR4, MIR924HG, IFNG-AS1, ABCG1, RBFOX1, ABCB11, TLR5, and ANK3) that may modulate the response to corticoid and immunomodulator therapies in COVID-19 patients. Enrichment analyses revealed overrepresentation of genes involved in the innate immune system, drug ADME, viral infection, and the programmed cell death pathways associated with the response phenotypes. <b>Conclusions</b>: Our study provides an initial framework for understanding the genetic determinants of treatment response in COVID-19 patients, offering insights that could inform precision medicine approaches for future epidemics.

BiomedicinesVol. 13(3)
Universidad Complutense de Madrid (ES), Universidad de Cantabria (ES), Universitat de València (ES), Universidade de Santiago de Compostela (ES), Instituto de Salud Carlos III (ES), Universitat Internacional de Catalunya (ES), Research Institute Hospital 12 de Octubre (ES), Hospital Universitario Nuestra Señora de Candelaria (ES), Universidad Fernando Pessoa Canarias (ES), University Hospital Mútua de Terrassa (ES), Marqués de Valdecilla University Hospital (ES), Hospital Universitario 12 De Octubre (ES), Instituto Tecnológico y de Energías Renovables (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Center for Research in Molecular Medicine and Chronic Diseases (ES), Instituto de Investigación Marqués de Valdecilla (ES), Centro de Investigación Biomédica en Red (ES), Fundación Pública Galega de Medicina Xenómica (ES), Universidad José Cecilio del Valle (HN), Hospital Universitario Fundación Jiménez Díaz (ES), Mútua Terrassa (ES), Instituto Murciano de Investigación Biosanitaria (ES), Servicio Murciano de Salud (ES), Instituto de Investigación Sanitaria de Santiago (ES), Servicio Gallego de Salud (ES), Instituto de Investigación de Enfermedades Raras (ES), Instituto de Investigación Sanitaria La Fe (ES), Universidad Autónoma de Madrid (ES), Universidad Católica de Murcia (ES), Universidad de Murcia (ES), Tecnológico de Monterrey (MX)
Fundación Canaria de Investigación y Salud, European Commission, Xunta de Galicia, Instituto de Salud Carlos III, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 95%
COVID-19 Clinical Research Studies
DOIOpen Access PDFOpenAlex
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