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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1422349
This article is part of the Research Topic Immunogenetics in times of COVID-19 pandemic View all 17 articles

Genetic Signatures of AKT1 Variants Associated with Worse COVID-19 Outcomes -A Multicentric Observational Study

Provisionally accepted
Ingrid M. Almeida Ingrid M. Almeida 1Bruna R. Tosta Bruna R. Tosta 1Laiane D. Pena Laiane D. Pena 1Hatilla d. Silva Hatilla d. Silva 1Fabiane d. Goes Fabiane d. Goes 2Nívia N. Silva Nívia N. Silva 2João Victor A. Cruz João Victor A. Cruz 1Mailane d. Silva Mailane d. Silva 1Jéssica F. Araújo Jéssica F. Araújo 1Juliana Rodrigues Juliana Rodrigues 1Gabriella Oliveira Gabriella Oliveira 3Ricardo G. Figueiredo Ricardo G. Figueiredo 4Sara VAZ Sara VAZ 5Iris Montaño-Castellón Iris Montaño-Castellón 5Daniele Santana Daniele Santana 5Alex J. Torres Alex J. Torres 2Fabyan E. Beltrao Fabyan E. Beltrao 6Valdirene Leão Carneiro Valdirene Leão Carneiro 7Gubio Campos Gubio Campos 2CARLOS BRITES CARLOS BRITES 5Vitor Fortuna Vitor Fortuna 2Camila A. Figueiredo Camila A. Figueiredo 1Soraya C. Trindade Soraya C. Trindade 2,4Helton E. Ramos Helton E. Ramos 2Ryan D. Costa Ryan D. Costa 1*
  • 1 Laboratory of Immunopharmacology and Molecular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil
  • 2 Other, Salvador, Brazil
  • 3 Instituto Couto Maia, Salvador, Brazil
  • 4 State University of Feira de Santana, Feira de Santana, Bahia, Brazil
  • 5 Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Bahia, Brazil
  • 6 Lauro Wanderley University Hospital, Federal University of Paraíba, Joao Pessoa, Brazil
  • 7 Department of Life Sciences, State University of Bahia, Salvador, Brazil

The final, formatted version of the article will be published soon.

    Introduction: The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes. Methods: Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants. Results: The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. Discussion: Our findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

    Keywords: AKT1, COVID-19, severity, polymorphism, Immunogenetics

    Received: 23 Apr 2024; Accepted: 18 Sep 2024.

    Copyright: © 2024 Almeida, Tosta, Pena, Silva, Goes, Silva, Cruz, Silva, Araújo, Rodrigues, Oliveira, Figueiredo, VAZ, Montaño-Castellón, Santana, Torres, Beltrao, Carneiro, Campos, BRITES, Fortuna, Figueiredo, Trindade, Ramos and Costa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ryan D. Costa, Laboratory of Immunopharmacology and Molecular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.