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Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α

  • Maria Alice Freitas Queiroz,
  • Wandrey Roberto dos Santos Brito,
  • Keise Adrielle Santos Pereira,
  • Leonn Mendes Soares Pereira,
  • Ednelza da Silva Graça Amoras,
  • Sandra Souza Lima,
  • Erika Ferreira dos Santos,
  • Flávia Póvoa da Costa,
  • Kevin Matheus Lima de Sarges,
  • Marcos Henrique Damasceno Cantanhede,
  • Mioni Thieli Figueiredo Magalhães de Brito,
  • Andréa Luciana Soares da Silva,
  • Mauro de Meira Leite,
  • Maria de Nazaré do Socorro de Almeida Viana,
  • Fabíola Brasil Barbosa Rodrigues,
  • Rosilene da Silva,
  • Giselle Maria Rachid Viana,
  • Tânia do Socorro Souza Chaves,
  • Adriana de Oliveira Lameira Veríssimo,
  • Mayara da Silva Carvalho,
  • Daniele Freitas Henriques,
  • Carla Pinheiro da Silva,
  • Juliana Abreu Lima Nunes,
  • Iran Barros Costa,
  • Izaura Maria Vieira Cayres-Vallinoto,
  • Igor Brasil-Costa,
  • Juarez Antônio Simões Quaresma,
  • Luiz Fábio Magno Falcão,
  • Eduardo José Melo dos Santos,
  • Antonio Carlos Rosário Vallinoto

摘要

The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.