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

TL;DR

This study shows that severe and long-term effects of COVID-19 are linked to increased activity of the cGAS-STING pathway and inflammatory markers like IFN-α.

Contribution

The study identifies a potential role of the cGAS-STING pathway in both severe and long-term inflammation following SARS-CoV-2 infection.

Findings

Severe acute COVID-19 is associated with higher cGAS, STING, IFN-α, TNF-α, and IL-6 levels.

Long COVID is linked to elevated cGAS, STING, and IFN-α levels.

The cGAS-STING pathway may drive systemic inflammation in severe and post-COVID-19 conditions.

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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