Neuronal, gastrointestinal, hepatic system and COVID-19
COVID-19 leads to lung injury, ARDS, and respiratory failure. The
respiration is mainly regulated by the respiratory center, which is
located in the medulla oblongata and pons, in the brain stem
(Ikeda et al., 2017). Reports show that
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and SARS-CoV
infect the brain stem leading to neurological complications
(Algahtani, Subahi & Shirah, 2016;
Arabi et al., 2015;
Hwang, 2006;
McCray et al., 2007;
Tsai et al., 2004). Growing evidence
shows that patients infected with SARS-CoV-2 present neurological
symptoms like headache, nausea, vomiting, cerebrovascular disease,
skeletal muscle injury and impaired consciousness
(Li, Bai & Hashikawa, 2020;
Mao et al., 2020). The consciousness is
regulated by the reticular activating system via activation of the
cerebral cortex and here arises a question that could SARS-CoV-2 alter
the reticular activating system and as well, brain stem function.
Aforementioned, SARS-COV-2 induces lung injury, alters RAAS system in
the pneumocytes which leads to the production of cytokines and cytokine
storm has been observed in patients underlying with pre-existing
diseases such as diabetes, myocardial injury. Yarlagadda et al. reported
that cytokines can cross the blood-brain barrier and cause significant
brain damage (Yarlagadda, Alfson &
Clayton, 2009). Further, circulating cytokines alters the hypothalamus
function which regulates body temperature and causes high fever; a
common symptom in COVID-19 patients
(Netea, Kullberg & Van der Meer, 2000).
Xia et al. reported that neuronal ACE 2 plays an important role in the
compensatory regulation of neurogenic hypertension in mice due to
dysregulated RAAS (Feng et al., 2010).
Hence, if SARS-CoV-2 crosses the blood-brain barrier then it might
interact with neuronal ACE 2 which can affect the brain functions and
capable enough to induce fatal neurological changes. Further fever,
pneumonia is a common symptom among COVID-19 disease but patients are
also reporting with gastrointestinal issues like abdominal pain,
anorexia, vomiting and diarrhea (Pan et
al., 2020; Song et al., 2020;
Wong & Lui, 2020;
Zhang et al., 2020a). Wang et al.
reported that respiratory influenza virus infection induces injury in
intestine cells, altered the intestinal microbiota composition, enhances
the production of the pro-inflammatory cytokine, altered immune cells
functions and induces Th17 cell-dependent inflammation
(Wang, Li, Wei, Lian, Sun & Tian, 2014).
Hamming et al. reported that ACE 2 is most profusely present in the
epithelial cells of the intestine, duodenum, jejunum and ileum which is
a pivotal entry point of SARS-CoV-2 and may infect the intestinal cells,
alter the functioning of immune cells, imbalance the microbiota
composition, impaired the intestinal function and causes diarrhea
(Hamming, Timens, Bulthuis, Lely, Navis &
van Goor, 2004b). Further, several reports are advocating that
detection of SARS-CoV-2 in the stools samples of COVID-19 patients which
may strengthen the fact that invasion of the virus to the intestine and
incidence of diarrhea. Hence, there would be chances of virus
transmission through the fecal-oral route
(Wang et al., 2020a;
Wu et al., 2020;
Zhang et al., 2020b).
Non-alcoholic steatohepatitis (NASH), which is characterized by liver
cell injury with high levels of pro-inflammatory cytokines that makes
COVID-19 patients more prone to additive cytokine burden leading to
severe liver damage that amplify the risk for liver fibrosis and
carcinogenesis (Syn, Choi & Diehl,
2009). Further, patients with non-alcoholic fatty liver diseases
(NAFLD) and NASH have impaired intestinal permeability with a disrupted
tight junction in the intestine, altered gut microbiota, increased
production of endotoxins (Lau, Carvalho &
Freitas, 2015; Takaki, Kawai & Yamamoto,
2013). Lau et al. reported that liver received about 70% of blood
supply from the intestine and this enhance the endotoxin translocation
from gut to the liver, which in turn to activates toll-like receptors
which further promotes inflammation and fibrosis in the liver
(Lau, Carvalho & Freitas, 2015).
Further, there is evidence of SARS-CoV-2 infection in the intestine and
is presence in faecal samples. Therefore, due to impaired permeability
of intestinal tight junction virus may invade the hepatic tissue and may
further aggravate the cytokine release in NASH patients. Moreover,
reports show that ACE 2 is expressed in the epithelial cells of the bile
duct and hepatic tissue with lower abundance but the chronic liver
injury upregulates the hepatic ACE 2 expression which is a key entry
point for SARS-CoV-2 (Huang et al., 2009;
Paizis et al., 2005). Hence, NAFLD and
NASH patients with the high level of cytokines are more prone to the
cytokine storm and this may induce irreversible damage of hepatic tissue
and at later stage liver transplantation can only be viable option.
Further, careful monitoring is needed among patients on the drugs that
have a potential to upregulates the ACE 2.