IL-18: The Forgotten Cytokine in Dengue Immunopathogenesis.

Dengue fever is an infection by the dengue virus (DENV) transmitted by vector mosquitoes. It causes many infections in tropical and subtropical countries every year, thus posing a severe disease threat. Cytokine storms, one condition where many proinflammatory cytokines are mass-produced, might lead to cellular dysfunction in tissue/organ failures and often facilitate severe dengue disease in patients. Interleukin- (IL-) 18, similar to IL-1ß, is a proinflammatory cytokine produced during inflammation following inflammasome activation. Inflammatory stimuli, including microbial infections, damage signals, and cytokines, all induce the production of IL-18. High serum IL-18 is remarkably correlated with severely ill dengue patients; however, its possible roles have been less explored. Based on the clinical and basic findings, this review discusses the potential immunopathogenic role of IL-18 when it participates in DENV infection and dengue disease progression based on existing findings and related past studies.

Monocyte Distribution Width, Neutrophil-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio Improves Early Prediction for Sepsis at the Emergency.

(1) Background: Sepsis is a life-threatening condition, and most patients with sepsis first present to the emergency department (ED) where early identification of sepsis is challenging due to the unavailability of an effective diagnostic model. (2) Methods: In this retrospective study, patients aged ≥20 years who presented to the ED of an academic hospital with systemic inflammatory response syndrome (SIRS) were included. The SIRS, sequential organ failure assessment (SOFA), and quick SOFA (qSOFA) scores were obtained for all patients. Routine complete blood cell testing in conjugation with the examination of new inflammatory biomarkers, namely monocyte distribution width (MDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), was performed at the ED. Propensity score matching was performed between patients with and without sepsis. Logistic regression was used for constructing models for early sepsis prediction. (3) Results: We included 296 patients with sepsis and 1184 without sepsis. A SIRS score of >2, a SOFA score of >2, and a qSOFA score of >1 showed low sensitivity, moderate specificity, and limited diagnostic accuracy for predicting early sepsis infection (c-statistics of 0.660, 0.576, and 0.536, respectively). MDW > 20, PLR > 9, and PLR > 210 showed higher sensitivity and moderate specificity. When we combined these biomarkers and scoring systems, we observed a significant improvement in diagnostic performance (c-statistics of 0.796 for a SIRS score of >2, 0.761 for a SOFA score of >2, and 0.757 for a qSOFA score of >1); (4) Conclusions: The new biomarkers MDW, NLR, and PLR can be used for the early detection of sepsis in the current sepsis scoring systems.

Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods.

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.