Abstract
BackgroundHyperinflammation with dysregulated production of galectins and cytokines may develop in COVID-19 or adult-onset Still’s disease (AOSD). Given the similar clinical features in both diseases, it is necessary to identify biomarkers that can differentiate COVID-19 from AOSD. However, the related data remain scarce currently.MethodsIn this cross-sectional study, plasma levels of galectin-3, galectin-9, and soluble TIM-3 (sTIM-3) were determined by ELISA in 55 COVID-19 patients (31 non-severe and 24 severe), 23 active AOSD patients, and 31 healthy controls (HC). The seropositivity for SARS-CoV-2 was examined using an immunochromatographic assay, and cytokine profiles were determined with the MULTIPLEX platform.ResultsSignificantly higher levels of galectin-3, galectin-9, IL-1β, IL-1Ra, IL-10, IFN-α2, IL-6, IL-18, and TNF-α were observed in severe COVID-19 and active AOSD patients compared with HC (all p<0.001). AOSD, but not COVID-19, showed significantly higher IFN-γ and IL-17A compared with HC (both p<0.01). Moreover, active AOSD patients had 68-fold higher IL-18 levels and 5-fold higher ferritin levels than severe COVID-19 patients (both p<0.001). IL-18 levels at the cut-off value 190.5pg/mL had the highest discriminative power for active AOSD and severe COVID-19, with AUC 0.948, sensitivity 91.3%, specificity 95.8%, and accuracy of 91.5% (p<0.005). Multivariate regression analysis revealed IL-18 as a significant predictor of active AOSD (p<0.05).ConclusionActive AOSD patients share features of hyperinflammation and cytokine storm with severe COVID-19 patients but possess a distinct cytokine profile, including elevated IL-18, IL-6, IFN-γ, and IL-17A. IL-18 is a potential discriminator between AOSD and COVID-19 and may significantly predict active AOSD.
Highlights
More than 120 million people had been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 2 million people had died of coronavirus disease 2019 (COVID-19) by March 2021
COVID-19 patients had a higher proportion of pulmonary involvement (56.4% vs. 0.0%, p
Gal-9 levels were significantly higher in non-severe COVID-19, severe COVID19, and active AOSD patients compared with healthy controls (HC)
Summary
More than 120 million people had been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 2 million people had died of coronavirus disease 2019 (COVID-19) by March 2021. COVID-19 patients tend to have elevated acute phase reactants and ferritin levels, and lymphocytopenia [1, 2]. In response to SARS-COV-2 infection, cytokine production may be rapidly dysregulated, leading to a systemic hyperinflammation status, the so-called cytokine storm [3, 4]. A variety of inflammatory or anti-inflammatory cytokines, such as interleukin (IL)-1b, IL-6, IL-8, IL-10, and interferon (IFN)-g, were elevated in severe COVID-19 patients [3, 4]. Hyperinflammation with dysregulated production of galectins and cytokines may develop in COVID-19 or adult-onset Still’s disease (AOSD).
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