Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes - a multicentric observational study

• Published in: Frontiers in immunology Vol. 15; p. 1422349
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08-10-2024
• Subjects: Adult; Aged; AKT1; COVID-19; COVID-19 - genetics; COVID-19 - immunology; COVID-19 - mortality; Cytokines - blood; Cytokines - genetics; Female; Fibrin Fibrinogen Degradation Products - analysis; Fibrin Fibrinogen Degradation Products - metabolism; Humans; immunogenetics; Immunology; Male; Middle Aged; polymorphism; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-akt - genetics; SARS-CoV-2 - physiology; severity; Severity of Illness Index; COVID-19; severity; AKT1; immunogenetics; polymorphism
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1422349

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
gene associated with severe COVID-19 outcomes.
Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the
variants.
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.
Our findings contribute to understanding the influence of the
gene variants on the immunological damage in individuals infected with SARS-CoV-2.