Mechanisms of CSS in COVID-19
The cytokine storm in COVID-19 may vary from the cytokine storms in
other clinical settings. It was revealed by autopsy findings, that the
lymphoid tissues were destroyed in COVID-19 patients, which is rare from
CSS in sepsis and CAR T-cell therapy. Spleen and lymph node atrophy are
observed in patients with COVID-19, while lymphadenopathy and
splenomegaly are more common in other CSS-related diseases. However, the
specific mechanisms for these differences remain unclear and need to be
further studied [9].
Coronaviruses (CoVs) are enveloped single-stranded RNA viruses, which
have caused two marked pandemics SARS and MERS [9]. Spike (S)
proteins of coronaviruses, including the SARS-CoV, facilitate entry into
their target cells via the interaction with angiotensin-converting
enzyme 2 (ACE2), a functional cellular receptor, which is highly
expressed in vascular endothelial cells, alveolar epithelial cells,
intestinal epithelial cells and renal proximal tubular cells. ACE2
suppresses angiotensin Ⅱ(AngⅡ) and activates the formation of
angiotensin 1–7, a which is a vasodilator heptapeptide. The binding of
the coronavirus spike protein to ACE2 leads to the down-regulation of
ACE2, which in turn results in excessive production of vasoconstrictor
AngⅡ and reduced production of vasodilator angiotensin 1–7.
Furthermore, AngⅡ binds to the angiotensin receptor 1 (AT1R) and plays a
role of proinflammatory cytokine. The AngⅡ-AT1R axis activates NF-κB and
metalloprotease 17 (ADAM17), which stimulates the production of the
epidermal growth factor receptor (EGFR) ligands and TNF-α, which
activate the IL-6 amplifier (IL-6 Amp), and lead to a hyperinflammatory
status, resulting in increased vascular permeability of the lungs
[10].
A retrospective study also found higher plasma concentrations of IL-2,
IL-7, IL-10, IP-10, MCP-1, and TNF-α in intensive care unit (ICU)
patients compared with nonsevere patients, suggesting a cytokine storm
in severe patients [11].