4.1 The respiratory system damaged in COVID-19
The lung is the most preliminary target organ for SARS-Cov-2 infection,
and pneumonia is the most common complication seen in COVID-19 patients
with the occurrence of 79.1%(Xie et al. , 2020). As reported,
ARDS is one of the most severe complications in COVID-19 patients(Wanget al. , 2020). The down-regulation of ACE2 plays an important
role in the pathogenesis of severe lung failure after SARS-CoV
infection(Kuba et al. , 2005). Recent data showed that COVID-19
patients with COPD as coexisting disorder were more likely to progress
into severe cases, which may be related with the decrease of ACE2. It
has been reported that ACE2 exerted protective effects against multiple
organs injury via degrading Ang Ⅱ to Ang (1-7)(Kuba et al. ,
2010). For example, ACE2 knockout mice showed severe ARDS-like injury
pathology in the lungs comparing to the wild type controls. At the same
time, the respiratory symptoms can be alleviated by the treatment of
rhACE2 protein(Imai et al. , 2005). Meanwhile, a phase Ⅱ clinical
study found that the level of Ang Ⅱ decreased rapidly in serum and
Ang(1-7) increased after patients with ARDS treated with rhACE2(Khanet al. , 2017). Administration of rhACE2 could ameliorate
H5N1-induced lung injury in mice(Zou et al. , 2014). Furthermore,
previous studies of ACE insertion/deletion (I/D) polymorphism
correlation with severity of ARDS in humans(Jerng et al. , 2006;
Marshall et al. , 2002) and ACE inhibitors treatments in rodent
ARDS(Raiden et al. , 2002) have suggested that the RAAS could have
role in ARDS/acute lung injury (ALI). In addition to the treatment of
rhACE2 and ACEI/ARB, Ang (1-7) also has a positive effect on the
process. The ratio of ACE/ACE2 was positively correlated with the ARDS
and Ang (1-7) could prevent the symptoms due to the increase of
ACE2(Wösten-van et al. , 2011). Infusions of Ang (1-7) prevented
rats from acute lung lesions after oleic acid administration as seen
through a decrease in lung edema, myeloperoxidase activity, histological
lung injury score, and pulmonary vascular resistance(Klein et
al. , 2013). The same results could be observed in a pulmonary injury
model based on lipopolysaccharide (LPS)(Chen et al. , 2013). These
results convincingly proved that ACE2 is protective against lung injury
and upregulation of the ACE2/Ang (1-7) axis may be a therapeutic target
for patients with COVID-19.