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<p>The COVID-19 caused by SARS-CoV-2 has resulted in widely variable clinical outcomes. The virus relies on host metabolic pathways particularly the PI3K/AKT/mTOR axis, which regulate cell survival, metabolism, and viral replication. Genetic variants whitin this pathway may influence disease severity. This study evaluated variants in PI3K genes among 216 mild and 291 severe COVID-19 patients, focusing on rs3730089 (PIK3R1), rs785468 (PIK3R3), and rs11121484 (PIK3CD). Genotypes were evaluted in peripheral blood samples, inflammatory cytokines (IL-6 and TNF) were measured in plasma samples and immune cell profiles were assessed in peripheral blood mononuclear cells. The C allele of rs11121484 was associated with susceptibility to severe COVID-19, while rs785468 and rs3730089 were correlated with higher mortality risk. The presence of multiple risk alleles showed a cumulative effect on disease outcome. Patients with the GG genotype of rs3730089 had increased IL-6 levels, and carriers of risk alleles displayed reduced non-classic monocytes and CD4 + memory T cells. These findings indicate that PI3K single-nucleotide variants (SNVs) may exacerbate inflammation and immune dysregulation in COVID-19, contributing to severe outcomes. Overall, these results highlight a potential pathological role for PI3K SNVs in driving hyperinflammation in COVID-19 patients and may contributes to predicting the severe outcome of COVID-19 and better disease prognosis.</p>

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PI3K gene variants are associated with elevated IL-6 levels and COVID-19 severe outcomes in a multicenter study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Bruna Ramos Tosta,
  • João Victor Andrade Cruz,
  • Ingrid Marins de Almeida,
  • Laryssa Cardoso Calmon,
  • Laiane da Cruz Pena,
  • Hatilla dos Santos Silva,
  • Dyjaene de Oliveira Barbosa,
  • Isa Rita Brito de Morais,
  • Fabiane S. Reis-Goes,
  • Nívia N. Silva,
  • Gabriella Oliveira,
  • Sara Nunes Vaz,
  • Iris Montaño-Castellón,
  • Daniele Santana,
  • Ricardo Gassmann Figueiredo,
  • Fabyan Esberard de Lima Beltrão,
  • Valdirene Leão Carneiro,
  • Gubio Soares Campos,
  • Carlos Brites,
  • Vitor Fortuna,
  • Alex José Leite Torres,
  • Camila Alexandrina Figueiredo,
  • Soraya Castro Trindade,
  • Helton Estrela Ramos,
  • Ryan dos Santos Costa

摘要

The COVID-19 caused by SARS-CoV-2 has resulted in widely variable clinical outcomes. The virus relies on host metabolic pathways particularly the PI3K/AKT/mTOR axis, which regulate cell survival, metabolism, and viral replication. Genetic variants whitin this pathway may influence disease severity. This study evaluated variants in PI3K genes among 216 mild and 291 severe COVID-19 patients, focusing on rs3730089 (PIK3R1), rs785468 (PIK3R3), and rs11121484 (PIK3CD). Genotypes were evaluted in peripheral blood samples, inflammatory cytokines (IL-6 and TNF) were measured in plasma samples and immune cell profiles were assessed in peripheral blood mononuclear cells. The C allele of rs11121484 was associated with susceptibility to severe COVID-19, while rs785468 and rs3730089 were correlated with higher mortality risk. The presence of multiple risk alleles showed a cumulative effect on disease outcome. Patients with the GG genotype of rs3730089 had increased IL-6 levels, and carriers of risk alleles displayed reduced non-classic monocytes and CD4 + memory T cells. These findings indicate that PI3K single-nucleotide variants (SNVs) may exacerbate inflammation and immune dysregulation in COVID-19, contributing to severe outcomes. Overall, these results highlight a potential pathological role for PI3K SNVs in driving hyperinflammation in COVID-19 patients and may contributes to predicting the severe outcome of COVID-19 and better disease prognosis.