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

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2022-11, Vol.159, p.156020-156020, Article 156020
• Main Authors: Ziegler, Louise, Lundström, Annika, Havervall, Sebastian, Thålin, Charlotte, Gigante, Bruna
• Format: Article
• Language: English
• Subjects: Biomarker; Biomarkers; C-Reactive Protein; COVID-19; Cytokine Receptor gp130 - metabolism; Cytokine/IL-6; Epidemiology; Humans; Hyperplasia; Inflammation; Interleukin-6; Longitudinal Studies; Medicin och hälsovetenskap; Pandemics; Receptors, Interleukin-6 - metabolism; SARS-CoV-2; Sweden - epidemiology
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2022.156020

This figure was created with images from BioRender.com. [Display omitted] •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. 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. 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. 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. Classical signalling is the dominating IL-6 pathway in moderate-severe COVID-19.