PI3K gene variants are associated with elevated IL-6 levels and COVID-19 severe outcomes in a multicenter study
9 affiliations
- 1Laboratório de Imunofarmacologia e Biologia Molecular, Instituto de Ciências da Saúde, Universidade Federal da Bahia
- 2Laboratório de Imunologia e Biologia Molecular, Instituto de Ciências da Saúde, Universidade Federal da Bahia
- 3Instituto Couto Maia
- 4Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia
- 5Universidade Estadual de Feira de Santana
- 6Hospital Universitário Lauro Wanderley, Universidade Federal da Paraíba
- 7Departamento de Ciências da Vida, Universidade do Estado da Bahia
- 8Laboratório de Virologia, Instituto de Ciências da Saúde, Universidade Federal da Bahia
- 9Programa de Pós-Graduação em Processos Interativos de Órgãos e Sistema, Instituto de Saúde e Ciência, Universidade Federal da Bahia
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.
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BibTeX
@article{tosta2026pi3k,
title = {{PI3K gene variants are associated with elevated IL-6 levels and COVID-19 severe outcomes in a multicenter study}},
author = {Bruna Ramos Tosta and João Victor Andrade Cruz and Ingrid Marins de Almeida and Laryssa Cardoso Calmon and Laiane da Cruz Pena and Hatilla dos Santos Silva and Dyjaene de Oliveira Barbosa and Isa Rita Brito de Morais and Fabiane S. Reis-Goes and Nívia N. Silva and Gabriella Oliveira and Sara Nunes Vaz and Iris Montaño-Castellón and Daniele Santana and Ricardo Gassmann Figueiredo and Fabyan Esberard de Lima Beltrão and Valdirene Leão Carneiro and Gubio Soares Campos and Carlos Brites and Vitor Fortuna and Alex José Leite Torres and Camila Alexandrina Figueiredo and Soraya Castro Trindade and Helton Estrela Ramos and Ryan dos Santos Costa},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-57773-y},
url = {https://doi.org/10.1038/s41598-026-57773-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - PI3K gene variants are associated with elevated IL-6 levels and COVID-19 severe outcomes in a multicenter study
AU - Bruna Ramos Tosta
AU - João Victor Andrade Cruz
AU - Ingrid Marins de Almeida
AU - Laryssa Cardoso Calmon
AU - Laiane da Cruz Pena
AU - Hatilla dos Santos Silva
AU - Dyjaene de Oliveira Barbosa
AU - Isa Rita Brito de Morais
AU - Fabiane S. Reis-Goes
AU - Nívia N. Silva
AU - Gabriella Oliveira
AU - Sara Nunes Vaz
AU - Iris Montaño-Castellón
AU - Daniele Santana
AU - Ricardo Gassmann Figueiredo
AU - Fabyan Esberard de Lima Beltrão
AU - Valdirene Leão Carneiro
AU - Gubio Soares Campos
AU - Carlos Brites
AU - Vitor Fortuna
AU - Alex José Leite Torres
AU - Camila Alexandrina Figueiredo
AU - Soraya Castro Trindade
AU - Helton Estrela Ramos
AU - Ryan dos Santos Costa
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-57773-y
UR - https://doi.org/10.1038/s41598-026-57773-y
AB - 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.
SN - 2045-2322
ER -