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

  • Sci Rep. 2024 Feb 29;14(1):4974. doi: 10.1038/s41598-024-55696-0.
Maria Alice Freitas Queiroz  1  2 ,  Wandrey Roberto Dos Santos Brito  3  4 ,  Keise Adrielle Santos Pereira  3  4 ,  Leonn Mendes Soares Pereira  3  4 ,  Ednelza da Silva Graça Amoras  3 ,  Sandra Souza Lima  3 ,  Erika Ferreira Dos Santos  4  5 ,  Flávia Póvoa da Costa  4  5 ,  Kevin Matheus Lima de Sarges  4  5 ,  Marcos Henrique Damasceno Cantanhede  4  5 ,  Mioni Thieli Figueiredo Magalhães de Brito  5 ,  Andréa Luciana Soares da Silva  5 ,  Mauro de Meira Leite  5 ,  Maria de Nazaré do Socorro de Almeida Viana  4  5 ,  Fabíola Brasil Barbosa Rodrigues  4  5 ,  Rosilene da Silva  4  5 ,  Giselle Maria Rachid Viana  6 ,  Tânia do Socorro Souza Chaves  6  7 ,  Adriana de Oliveira Lameira Veríssimo  8 ,  Mayara da Silva Carvalho  8 ,  Daniele Freitas Henriques  9 ,  Carla Pinheiro da Silva  9 ,  Juliana Abreu Lima Nunes  10 ,  Iran Barros Costa  10  11 ,  Izaura Maria Vieira Cayres-Vallinoto  3  4 ,  Igor Brasil-Costa  10  11 ,  Juarez Antônio Simões Quaresma  11  12 ,  Luiz Fábio Magno Falcão  12 ,  Eduardo José Melo Dos Santos  4  5 ,  Antonio Carlos Rosário Vallinoto  3  4  11
Affiliations
  • 1. Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil. [email protected].
  • 2. Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil. [email protected].
  • 3. Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.
  • 4. Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.
  • 5. Laboratory of Genetics of Complex Diseases, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.
  • 6. Laboratory of Basic Research On Malaria, Parasitology Section, Evandro Chagas Institute, Health and Environment Surveillance Secretariat, Brazilian Ministry of Health, Ananindeua, Brazil.
  • 7. School of Medicine, Institute of Medical Sciences, Federal University of Pará, Belém, Pará, Brazil.
  • 8. Belém Adventist Hospital, Belém, Brazil.
  • 9. Arbovirology and Hemorrhagic Fevers Section, Evandro Chagas Institute, Health and Environment Surveillance Secretariat, Brazilian Ministry of Health, Ananindeua, Brazil.
  • 10. Laboratory of Immunology, Section of Virology, Instituto Evandro Chagas, Health and Environment Surveillance Secretariat, Brazilian Ministry of Health, Ananindeua, Brazil.
  • 11. Graduate Program in Virology, Evandro Chagas Institute, Department of Science, Technology, Innovation and Strategic Health Inputs, Ministry of Health of Brazil, Ananindeua, Brazil.
  • 12. Center of Biological and Health Sciences, University of the State of Pará, Belém, Brazil.
PMID: 38424312 DOI: 10.1038/s41598-024-55696-0
Abstract

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.