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

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.

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Publication Details

Journal
Scientific Reports
Published
2026-07-17
DOI
https://doi.org/10.1038/s41598-026-57773-y
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Ricardo G. Figueiredo, Laiane da Cruz Pena, Soraya Castro Trindade, Ryan dos Santos Costa et al.
Scientific Reports
COVID-19 Clinical Research Studies
article

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

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

Abstract

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.

Scientific Reports
Universidade Federal da Bahia (BR), Universidade do Estado da Bahia (BR), Universidade Federal da Paraíba (BR), Universidade Estadual de Feira de Santana (BR), Complexo Hospitalar Universitário Professor Edgard Santos (BR), Hospital Universitário Lauro Wanderley (BR)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Fundação de Amparo à Pesquisa do Estado da Bahia
Good health and well-being
Openalex Percentile: Top 8%
COVID-19 Clinical Research Studies
DOIOpen Access PDFOpenAlex
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