Pharmacogenomic Study of SARS-CoV-2 Treatments: Identifying Polymorphisms Associated with Treatment Response in COVID-19 Patients
Alexandre Serra-Llovich, Natalia Cullell, Olalla Maroñas, María José Herrero, Raquel Cruz, Berta Almoguera, Carmen Ayuso, Rosario López-Rodríguez, Elena Domínguez-Garrido, Rocio Ortiz-Lopez, María Barreda-Sánchez, Marta Corton, David Dalmau, Esther Calbo, Lucía Boix-Palop, Beatriz Dietl, Anna Sangil, Almudena Gil-Rodriguez, Encarna Guillén-Navarro, Esther Mancebo, Saúl Lira-Albarrán, Pablo Minguez, Estela Paz-Artal, Gladys G Olivera, Sheila Recarey-Rama, Luis Sendra, Enrique G Zucchet, Miguel López De Heredia, Carlos Flores, José A Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Ángel Carracedo, María J Arranz
Biomedicines, doi:10.3390/biomedicines13030553
Background/Objectives: 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. Methods: 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 (n = 849), corticoids (n = 2202), and the combined cohort of both treatments (n = 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. Results: 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. Conclusions: 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.
Conflicts of Interest: The authors declare no conflicts of interest.
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"DOI": "10.3390/biomedicines13030553",
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"abstract": "<jats:p>Background/Objectives: 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. Methods: 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 (n = 849), corticoids (n = 2202), and the combined cohort of both treatments (n = 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. Results: 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. Conclusions: 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.</jats:p>",
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