3.4 Inflammatory sepsis in COVID-19
In response to high neutrophilia with progressive lymphopenia
established in COVID-19, viral sepsis may be promoted as a result of
systemic uncontrolled inflammation induced by neutrophils with further
worsening of tissue injury (Li et al., 2020a), that is in consistence
with the final diagnosis emphasized the existence of a septic shock
among COVID-19 patients with profound lymphopenia (Dallan et al., 2020).
Sepsis is a syndrome that has attracted the attention worldwide because
of its high mortality rate of about 50–80 %. It is widely recognized
as a kind of systemic inflammatory response that caused by severe
bacterial infections and tissue injuries (Annane et al., 2005). Sepsis
itself may share in the subsequent release of inflammatory factors (IL-6
and TNF-α) that could eventually aggravate the existing inflammation
(Molano Franco et al., 2019).
Developing sepsis could lead to multiple organ dysfunction, shock, and
even death, which are not caused directly by the invading pathogens; but
as a result of inflammation (Crowther, 2001; Mantzarlis et al., 2017).
During sepsis, there is an extensive crosslink between increased
inflammation, endothelial dysfunction and hyper-coagulopathy, in which
the microvascular dysfunction was documented to be one of important
sepsis hallmarks (Schouten et al., 2008).
3.5 TGF-β1-induced
pulmonary fibrosis in COVID-19
Giving the reported evidence of induced endothelial
dysfunction, pulmonary fibrosis
may be also prompted as a substantial problem during COVID-19 infection,
to the extent that pulmonary post-mortem findings in fatal cases of
COVID-19 revealed the presence of extensive fibrotic features as
myofibroblastic proliferation or organizing pneumonia (George et al.,
2020). The vascular endothelial dysfunction could stimulate the fibrotic
consequences via secreting a peptide, namely endothelin-1 (ET-1)
(Elshazly et al., 2013), which could induce the release of transforming
growth factor- β1 (TGF-β1), a fibrogenic cytokine mainly implicated in
driving the pulmonary fibrosis development (Wermuth et al., 2016).