IL-6 signalling biomarkers in hospitalised patients with moderate to severe SARS-CoV-2 infection in a single centre study in Sweden. (November 2022)

• Record Type: Journal Article
• Authors: Ziegler, Louise; Lundström, Annika; Havervall, Sebastian; Thålin, Charlotte; Gigante, Bruna
• Is Part Of: Cytokine. Volume 159(2022)
• Publication Date: 2022-11
• Subjects: COVID-19 -- Inflammation -- Cytokine/IL-6 -- Biomarker -- Epidemiology; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2022.156020
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: This figure was created with images from BioRender.com . Highlights: Severe COVID-19 is associated with elevated interleukin 6 (IL-6) levels. Establishing which IL-6 pathway is active enables targeted treatment. Classical signalling was the dominating IL-6 pathway in severe COVID-19. Treatment with monoclonal IL-6 receptor antibodies is thus suitable. Abstract: Background: COVID-19 disease severity and need for intensive care has been associated with profound immune disturbances in which interleukin 6 (IL-6) is central. IL-6 signals through two pathways: classical IL-6 signalling with C-reactive protein (CRP) as a product is pivotal in the acute immune response against pathogens while IL-6 trans -signalling is involved in prolonged inflammation. We measured biomarkers of the IL-6 classical and trans -signalling pathways in patients with moderate or severe COVID-19 in the first wave of the COVID-19 pandemic. Method: In a longitudinal cohort study including patients admitted to Danderyd hospital, Stockholm, Sweden, with COVID-19 (n = 112), plasma IL-6 mirroring activity in both pathways, CRP as marker of classical signalling and the soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) as markers of trans -signalling were analysed at baseline. Potential differences in biomarker levels between groups of moderate and severe COVID-19 defined by care level, level of respiratory support and one-month mortality was analysed, as was correlations between biomarkers. In addition, levels 4 months after hospital admission were compared to those at baseline. Results: Levels of IL-6 and CRP were increased in severe COVID-19 whereas IL-6 trans -signalling markers (sIL-6R, sgp130) did not differ between the groups. CRP correlated positively with IL-6 in all patients while correlation with IL-6 could not be demonstrated for sIL-6R and sgp130 in either group. Levels of IL-6, CRP and sIL-6R were significantly decreased after 4 months whereas sgp130 levels increased. Conclusion: Classical signalling is the dominating IL-6 pathway in moderate-severe COVID-19.