ABSTRACT
Background: Hyperinflammation 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. Methods: In 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. Results: Significantly higher levels of galectin-3, galectin-9, IL-1ß, 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). Conclusion: Active 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.
Subject(s)
COVID-19 , Interleukin-18 , SARS-CoV-2 , Still's Disease, Adult-Onset , Adult , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , Cross-Sectional Studies , Female , Humans , Interleukin-18/blood , Interleukin-18/immunology , Male , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Still's Disease, Adult-Onset/blood , Still's Disease, Adult-Onset/immunologyABSTRACT
The COVID-19 pandemic has raised many issues not the least of which is the reason for its high variability in consequences to the infected person. In this opinion letter, we advocate that the dose and presentation of the infecting virus is a major factor that affects whether the outcome is subclinical, tissue damaging or even lethal following infection. We briefly describe the known effects of virus dose on the course COVID-19 and discuss practical maneuvers as well as largely untested procedures that can raise the threshold dose needed to break through barriers of resistance.