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).