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Comment
. 2020 May 27:11:1206.
doi: 10.3389/fimmu.2020.01206. eCollection 2020.

Could SARS-CoV-2-Induced Hyperinflammation Magnify the Severity of Coronavirus Disease (CoViD-19) Leading to Acute Respiratory Distress Syndrome?

A S Smiline Girija  1 , Esaki M Shankar  2 , Marie Larsson  3
Affiliations
Comment

Could SARS-CoV-2-Induced Hyperinflammation Magnify the Severity of Coronavirus Disease (CoViD-19) Leading to Acute Respiratory Distress Syndrome?

A S Smiline Girija et al. Front Immunol. .
No abstract available

Keywords: IL-1β; IL-6; TNF-α; corona virus disease 2019; cytokine storm.

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Figures

Figure 1
Figure 1
Proposed mechanism of induction of cytokine storm in coronavirus disease (CoViD-19). Following entry of SARS-CoV-2 into a susceptible host, the virus employs its spike protein to invade the respiratory airway epithelial cells via ACE2 receptors expressed on the cells causing damage to the upper respiratory epithelium. Several danger-associated molecular patterns, cellular stress factors (IL-1a, IL-33, HMGB1) and pro-inflammatory chemokines and chemoattractants (eg., CXCL8, CXCL10, C3a, C5a) are released that recruit several types of inflammatory cells (monocytes/macrophages, granulocytes and NK cells) that release IL-1β, IL-6, IL-18, TNF-α, IFN-γ and several other factors that can further trigger inflammation (also via NLRP3 and AIM2 inflammasome assembly and caspase-1 activation) especially in the lower respiratory tract. Mast cell, macrophage and endothelial activation also takes place to exaggerate the inflammatory cascade resulting in cytokine storm syndrome (or hypercytokinemia). Excessive cytokine release and binding to cytokine receptors lead to massive cytokine signaling that culminates in Fas-FasL/TRAIL-DR5-dependent signaling in endothelial cells causing their death, which erodes the blood vessel walls that results in vascular leakage. Intravascular coagulation also ensues leading to widespread damage of blood capillaries in the lungs. T cell death/depletion ensues via TNF-α and also expression of exhaustion molecules (PD-1) on CD4+ and CD8+ T cells (not shown) can result in poor anti-viral immune responses. Onset of acute respiratory distress syndrome can be fatal characterized by pneumonitis, pyrexia, myalgia, dyspnoea, loss of smell/taste and can lead to high mortality rates.
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