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

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

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Serra-Llovich A
  • Cullell N
  • Maroñas O
  • Cruz R
  • Almoguera B
  • Ayuso C
  • López-Rodríguez R
  • Domínguez-Garrido E
  • Ortiz-Lopez R
  • Barreda-Sánchez M
  • Corton M
  • Dalmau D
  • Calbo E
  • Boix-Palop L
  • Dietl B
  • Sangil A
  • Gil-Rodriguez A
  • Guillén-Navarro E
  • Mancebo E
  • Lira-Albarrán S
  • Minguez P
  • Paz-Artal E
  • Recarey-Rama S
  • Zucchet EG
  • López de Heredia M
  • Flores C
  • Riancho JA
  • Rojas-Martinez A
  • Lapunzina P
  • Carracedo Á
  • Arranz MJ
  • Scourge Cohort Group

Grupos

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-1a, 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.

Datos de la publicación

ISSN/ISSNe:
2227-9059, 2227-9059

Biomedicines  MDPI

Tipo:
Article
Páginas:
-
PubMed:
40149530
Factor de Impacto:
0,874 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 4

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Keywords

  • SARS-CoV-2; corticoids; immunomodulators; pharmacogenetics; precision medicine

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