الفهرس 
COVID-19
Increasing receptor-binding avidityOnly 14 pages are availabe for public view
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Abstract
The novel coronavirus (COVID-19) was declared as a global
pandemic by the World Health Organization (WHO) on March 11, 2020.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
pandemic has had a tremendous impact worldwide.
COVID-19 exhibits heterogeneous disease patterns due to variable
clinical factors, including age, gender, comorbidities, genetic makeup, and
acquired immune differences. Mapping virus-host interactions is critical to
understand disease progression. High mortality due to COVID-19 disease
has been a serious concern.
COVID-19 is a multisystemic disease regulated by an interplay of
immunological, inflammatory, and coagulative cascades. Patients with the
severe form of coronavirus disease have been frequently found to suffer
from both arterial and venous thrombotic events due to the presence of a
hypercoagulable state. This phenomenon, termed COVID-19–
associated coagulopathy.
At first, the vascular insults may be limited to the
pulmonary microvasculature, as the disease progresses, systemic
involvement occurs, culminating in distant organ thrombosis
and multiorgan dysfunction syndrome.
SARS-CoV-2 infection occurs through the interaction of the viral
protein Spike with the angiotensin II receptor (ACE 2), leading to an
increase of angiotensin II and activation of nicotinamide adenine
dinucleotide phosphate oxidase2 (NOX2), resulting in the release of both
reactive oxygen species (ROS) and inflammatory molecules. Also, NOX2
activated by the RNA viruse as consequence of upregulation of TLR-7.
The role of NOX2 in the promoting the coagulation state appeared
in upregulating endothelial- TF activation, activation of leucocytes induced
thrombomodulin oxidation, platelet activation and induction of vascular
wall inflammation.
Tissue factor (TF) is a high-affinity transmembrane protein
receptor and interact with factor (F)VII/VIIa. The TF-FVIIa complex is
Summary and Conclusion
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the primary initiator of blood coagulation and plays an essential role in
hemostasis.
TF-mediated extrinsic coagulation activation may be the
underlying cause of COVID-19 associated coagulopathy. Exposure to
pathogens results in rapid and transient upregulation of TF expression in
immune cells and non-immune cells (endothelial and epithelial cells).
Expression of TF on endothelial cells and leukocytes combined with
endothelial microinjuries (which expose subendothelial TF) results in
increased fibrin generation and formation of microthrombi.
The present study aimed to find out the relation between
NADPH oxidase and the thrombotic complications in COVID-19 infection
in Egyptian patients.
The current study was carried out on 180 subjects, 100 adult
hospital admitted COVID-19 patients and 80 apparently healthy subjects.
COVID-19 patients were classified into two groups; patients with TEEs
included 29 patients and patients without TEEs included 71 patients. They
were subjected to complete history taking, clinical examination and
assessment of hematological profile, biochemical profile, inflammatory
markers, coagulation profile, IL-6, tissue factor and NOX2.
The highest incidance of TEEs were appeared among criticaly ill
patients. COVID-19 patients with TEEs had significant higher levels of
WBCs count, neutrophil count, ALT, AST, urea, creatinine, LDH, CRP,
ferritin, procalcitonin, IL-6, INR, APTT, D-dimer, TF and NOX2 than
patients without TEEs. However, serum albumin level was significantly
lower in patients with TEEs.
NOX2 and TF were significantly positively correlated with each
other and positively correlated with laboratory variables such as IL-6,
procalcitonin, APTT and D-dimer. In contrast, they were significantly
negatively correlated with platelet count.
Patients who developed stroke complications had significant
higher levels of TF and NOX2 than other types of TEEs. ICU- admitted
patients and non- survived patients had significant higher levels of TF and
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NOX2. Also, patients with TEEs had lower survival rate when compared
with patients without TEEs.
It was found that the prognostic performance of NOX2 when
combined with IL-6 to predict thromboembolic events showed the highest
senstivity and specificity which were slightly higher than NOX2 alone.
It was found that the prognostic performance of NOX2 when
combined with IL-6 and TF when combined with IL-6 to predict mortality
showed the highest senstivity, while NOX2 level had the highest
specificity to predict mortality.
from this study, we concluded that:
High levels of NADPH oxidase2, tissue factor and IL-6 are
associated with increased incidances of the thromboembolic
complications, ICU admission and mortality rates in COVID-19 patients.
Therefore, they should be regularly investigated as predictor biomarkers of
COVID-19 bad outcome.