Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications

Abstract

Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.

Keywords: Coronavirus; Cytokine storm; Immune escape; Inflammation; SARS-CoV-2.

Graphical abstract

Fig. 1

Schematic diagram of the role IL-6 played in CD4⁺T cell differentiation. IL-6 incites näive CD4⁺T cells to differentiate into both Th2 cells, instead of Th1 cells, and Th17 cells, instead of Treg. Together with TGF-β, IL-6 leads to the activation of STAT3; thus relieving the repression of RORγt and promoting the Th17 cells transcriptional program. It has also been established that IL-17 produced by activated Th17 cells are able to trigger a positive-feedback loop of IL-6 expression through NF-κB and STAT3 signaling. Additionally, IL-6 prevents T cells from differentiating into Th1 cells through the inhibition of TNF-γ signaling by the upregulation of suppressor of cytokine signaling (SOCS1). IL-6 can also induce the production of endogenous IL-4, consequently driving the T cells to differentiate into Th2 cells. This, in turn, inhibits the differentiation and function of Th1 cells due to the cytokines produced from Th2 cells.