MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study

• Published in: International immunopharmacology 2023-12, Vol.125 (Pt B), p.111155-111155, Article 111155
• Main Authors: Tosta, Bruna Ramos, de Almeida, Ingrid Marins, da Cruz Pena, Laiane, Dos Santos Silva, Hatilla, Reis-Goes, Fabiane S, Silva, Nívia N, Cruz, João Victor Andrade, Dos Anjos Silva, Mailane, de Araújo, Jéssica Francisco, Rodrigues, Juliana Lopes, Oliveira, Gabriella, Figueiredo, Ricardo Gassmann, Vaz, Sara Nunes, Montaño-Castellón, Iris, Santana, Daniele, de Lima Beltrão, Fabyan Esberard, Carneiro, Valdirene Leão, Campos, Gubio Soares, Brites, Carlos, Fortuna, Vitor, Figueiredo, Camila Alexandrina, Trindade, Soraya Castro, Ramos, Helton Estrela, Costa, Ryan Dos Santos
• Format: Article
• Language: English
• Subjects: Adult; Aged; Case-Control Studies; COVID-19 - genetics; COVID-19 - immunology; COVID-19 - mortality; COVID-19 - pathology; Cytokines - blood; Female; Genetic Variation; Humans; Male; Middle Aged; Patient Acuity; Survival Analysis; TOR Serine-Threonine Kinases - genetics
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.111155

The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.