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Published Erratum
. 2020 Sep 18;134(17):2315-2317.
doi: 10.1042/CS-20200904_COR.

Correction: Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission

No authors listed
Published Erratum

Correction: Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission

No authors listed. Clin Sci (Lond). .
No abstract available

Keywords: COVID-19; Coronavirus; SARS-CoV-2; signaling pathway.

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Figures

Figure 2
Figure 2. Canonical ACE2 pathway links multiple organ damage in COVID-19
SARS-CoV-2 infection down-regulates ACE2 expression and leads to the production of pro-inflammatory mediators, such as IL-6 [1]. Angiotensin-I (Ang-I) is converted into Ang-II by the ACE in the extracellular space. ACE2 is able to further cleave Ang-II to Ang(1-7), which binds MasR receptors on the cell surface and promotes anti-inflammatory, vasodilation and anti-fibrotic effects [1]. Since ACE2 is down-regulated during viral infection, this event will lead to the accumulation of Ang-II and binding to AT1R receptors on cellular membrane. AT1R signals through JAK-STAT and induces fibrosis, pro-inflammatory gene expression and vasoconstriction [2,3]. Multiple organs express ACE2 and are target for SARS-CoV-2. As they lose ACE2-mediated protection, Ang-II signaling contributes to the pathological findings observed in COVID-19 patients, such as disseminated coagulopathy and acute tissue damage [4].
Figure 3
Figure 3. Signaling pathways involved in COVID-19 pathophysiology
Toll-like receptors (TLRs) 3 and TLR 7/8 recognize SARS-CoV-2 RNA and initiate the inflammatory cascade via type I and type II IFN gene expression and NF-κB nuclear translocation [5,6]. Via NF-κB, the expression of multiple pro-inflammatory genes is stimulated, including pro-IL-1β, pro-IL-18, TNF and IL-6 [7–9]. The virus is also recognized by cytoplasmic NLRP3, which forms, together with ASC and caspase-1 (Casp-1), the inflammasome complex that will cleave and release mature forms of IL-1β and IL-18 [10]. The cytokines IL-1β, IL-18 and TNF bind to specific receptors and promote further NF-κB nuclear translocation and phosphorylation of p38 MAPK, which will lead to great expression of pro-inflammatory cytokines and chemokines [11,12]. IL-6, an important player in COVID-19, binds IL-6R and gp130 receptors to activate JAK/STAT-3 pathway and then contribute to the CRS observed in COVID-19 patients [13].
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