@article{10902/36691,
year = {2025},
url = {https://hdl.handle.net/10902/36691},
abstract = {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-1, 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.},
organization = {This work was supported by the Instituto de Salud Carlos III (COV20_00622 to A.C.
and PI20/00876 to C.F.; stop-coronavirus: COV20/00181; BioFRAM project (PMP22/00056)) and
cofounded by the European Union (ERDF) ‘A way of making Europe’ and the Fundación Amancio
Ortega, Banco de Santander (to A.C.); Fundación Canaria Instituto de Investigación Sanitaria de
Canarias (PIFIISC23/05 to C.F.); ERA PerMed (JTC_2021; AC21_2/00039 from the Instituto de Salud
Carlos III to C.F.); Xunta de Galicia (Predoctoral Fellowship Programme 2024); and funds from
Next Generation EU as part of the actions of the Recovery Mechanism and Resilience (MRR). The
genotyping service was carried out at CEGEN-PRB3-ISCIII, supported by grant PT17/0019, of the PE
I+D+i 2013−2016, funded by ISCIII and ERDF.},
publisher = {Biomedicines, 2025,13(3), 553},
title = {Pharmacogenomic study of SARS-CoV-2 treatments: identifying polymorphisms associated with treatment response in COVID-19 patients},
author = {Serra Llovich, Alexandre and Cullell, Natalia and Maroñas, Olalla and José Herrero, María and Cruz, Raquel and Almoguera, Berta and Ayuso, Carmen and López Rodríguez, Rosario and Domínguez Garrido, Elena and Ortiz Lopez, Rocio and Barreda Sánchez, María and Corton, Marta and Dalmau, David and Calbo, Esther and Boix Palop, Lucía and Dietl, Beatriz and Sangil, Anna and Gil Rodriguez, Almudena and Riancho Moral, José Antonio and Guillén Navarro, Encarna},
}