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. alicefarma@hotmail.com.
2 Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil. alicefarma@hotmail.com.
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.

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