Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

There are reports of several respiratory viruses identified in the lung. However, the existence of dengue virus (DENV) particle is still in its infancy. We have thoroughly discussed the several components and traits of lung cells’ involvement in DENV infection in detail. In this chapter, our goal is to focus on unraveling the key elements of the epithelial microenvironment, microbiota of the lung niche and their participation in the spread of DENV infection and patient outcome. We also talked about the crucial aspect of the lung-gut axis, host and mosquito variables that may influence how a DENV infection progresses, and a potential connection between sepsis and lung damage after a DENV infection. We natively concentrate on the existence of dengue virus (DENV) in lung niche microbiota and aimed to emphasize the incidence of lung manifestations in dengue-infected individuals, their correlation with patient outcomes and the spread of DENV’s in the lung microenvironment. This report will introduce a new field of inquiry in finding critical underlying unknown cause of DENV infection and solving the puzzle of dengue diagnosis.