AUTHOR=de Almeida Ingrid Marins , Tosta Bruna Ramos , Pena Laiane da Cruz , Silva Hatilla dos Santos , Reis-Goes Fabiane S. , Silva Nívia N. , Cruz João Victor Andrade , Silva Mailane dos Anjos , de Araújo Jéssica Francisco , Rodrigues Juliana Lopes , Oliveira Gabriella , Figueiredo Ricardo Gassmann , Vaz Sara Nunes , Montaño-Castellón Iris , Santana Daniele , Torres Alex , Beltrão Fabyan Esberard de Lima , Carneiro Valdirene Leão , Campos Gubio Soares , Brites Carlos , Fortuna Vitor , Figueiredo Camila Alexandrina , Trindade Soraya Castro , Ramos Helton Estrela , Costa Ryan dos Santos TITLE=Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes – a multicentric observational study JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422349 DOI=10.3389/fimmu.2024.1422349 ISSN=1664-3224 ABSTRACT=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.