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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.
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1 Federal University of Pará, Laboratory of Virology, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249); Federal University of Pará, Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249)
2 Federal University of Pará, Laboratory of Virology, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249)
3 Federal University of Pará, Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249); Federal University of Pará, Laboratory of Genetics of Complex Diseases, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249)
4 Federal University of Pará, Laboratory of Genetics of Complex Diseases, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249)
5 Brazilian Ministry of Health, Laboratory of Basic Research On Malaria, Parasitology Section, Evandro Chagas Institute, Health and Environment Surveillance Secretariat, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442)
6 Brazilian Ministry of Health, Laboratory of Basic Research On Malaria, Parasitology Section, Evandro Chagas Institute, Health and Environment Surveillance Secretariat, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442); Federal University of Pará, School of Medicine, Institute of Medical Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249)
7 Belém Adventist Hospital, Belém, Brazil (GRID:grid.271300.7)
8 Brazilian Ministry of Health, Arbovirology and Hemorrhagic Fevers Section, Evandro Chagas Institute, Health and Environment Surveillance Secretariat, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442)
9 Brazilian Ministry of Health, Laboratory of Immunology, Section of Virology, Instituto Evandro Chagas, Health and Environment Surveillance Secretariat, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442)
10 Brazilian Ministry of Health, Laboratory of Immunology, Section of Virology, Instituto Evandro Chagas, Health and Environment Surveillance Secretariat, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442); Ministry of Health of Brazil, Graduate Program in Virology, Evandro Chagas Institute, Department of Science, Technology, Innovation and Strategic Health Inputs, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442)
11 Ministry of Health of Brazil, Graduate Program in Virology, Evandro Chagas Institute, Department of Science, Technology, Innovation and Strategic Health Inputs, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442); University of the State of Pará, Center of Biological and Health Sciences, Belém, Brazil (GRID:grid.419134.a)
12 University of the State of Pará, Center of Biological and Health Sciences, Belém, Brazil (GRID:grid.419134.a)
13 Federal University of Pará, Laboratory of Virology, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249); Federal University of Pará, Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Belém, Brazil (GRID:grid.271300.7) (ISNI:0000 0001 2171 5249); Ministry of Health of Brazil, Graduate Program in Virology, Evandro Chagas Institute, Department of Science, Technology, Innovation and Strategic Health Inputs, Ananindeua, Brazil (GRID:grid.419134.a) (ISNI:0000 0004 0620 4442)