Discussion
In our study, it was observed that laboratory parameters that have been
observed to have prognostic importance in COVID-19 patients increased in
correlation with the severity of the disease. In the evaluation of suPAR
and KIM-1 levels, it was observed that suPAR level was low compared to
moderate patients in severe patients, while KIM-1 level increased in
line with the severity of the disease. In the correlation of PaO2/FiO2
level with the parameters subject to our research, positive directional
correlation was observed with suPAR level, while negative directional
correlation was found with KIM-1 level.
SARS-CoV-2 is closely related to SARS-CoV and MERS-CoV, which are
responsible for past outbreaks with significant morbidity and mortality.
The rapid spread of COVID-19 has caused the pandemic and is now
spreading globally. So far, the number of people infected due to
COVID-19 is said to be over a hundred million, and the number is
increasing day by day 11.
Observing lymphopenia in most patients in the examination of laboratory
parameters of COVID-19 patients suggested that 2019nCoV similar to
SARS-CoV could have an effect on lymphocytes, especially T lymphocytes.
Virus particles emanating from the respiratory mucosa and infecting
other cells cause abnormal cytokine discharge in the body, which is
called a cytokine storm. T lymphocyte damage is also important in
cytokine storm formation 12. After the cytokine storm,
many proinflammatory cytokines, especially TNF-alpha, IL-1, IL-2, IL-6,
nitric oxide, are released. These cytokines can cause increased vascular
permeability, causing deterioration in tissue perfusion, as well as
endothelial damage and microtombus formation. This increase in vascular
permeability causes fluid accumulation in lung tissue and the
interstitial area, resulting in an acute setting of respiratory failure.
Positive results have been reported that IL-1 and IL-6 antagonists can
be used to control this setting 13, 14.
The dense presence of the KIM-1 molecule in T cells gave it a different
name: T cell/transmembrane, immunoglobulin, and mucin (TIM-1). The
interaction of KIM-1/TIM-1 with T cells has played an important role in
immune response, allergy, asthma, autoimmune diseases and response to
viral infections 5. In the preliminary evaluation of
clinical interaction between KIM-1/TIM-1 and COVID-19 patients, the
relationship with acute kidney damage was evaluated in the foreground15. Kim-1/TIM-1 has been observed to facilitate the
entry of the virus into the cell, such as ACE-2 receptors via IgV. It
has been observed that increased proinflammatory cytokine levels as a
result of increased virulence may cause further progression of kidney
damage 6. In studies with SARS-CoV and MERS-CoV, it
was also determined that the IgV unit provides ease of entry for other
members of the family 16. In another publication,
which is also in the evaluation phase, it has been suggested that
KIM-1/TIM-1 receptors are high in the lungs and kidneys and that the
observed TW-37 molecule, which can inhibit anth-KIM-1/TIM-1 antibody and
endocytosis, can be used as a therapeutic target 5.
Humoral immunity plays an important role in controlling infection after
the development of viremia. One of the chemotactic agents that plays an
important role in the migration of these cells is uPAR. uPAR and its
serum-dissolved form, suPAR, mediate the transformation of plasminogen
into a plasmin.
By enabling a number of proteolytic activities to take place in the
placenum extracellular matrix, it facilitates the migration of cells
that play a role in the immune response 8. Studies
investigating the relationship of suPAR level with inflammatory diseases
found that the level of diabetes mellitus, coronary artery disease,
community origin, ventilator-related pneumonias, smoking, acute
enflaming of chronic obstructive pulmonary disease and sepsis increased
compared to the healthy control group 17, 18, 19, 20,
21, 22, 23, 24, 25. It has also been shown that early mortality may
have an important place in the pre-examination and survey in patients
with sepsis. In the study evaluating patients with COVID-19, it was also
assessed that there may be an early biomarker in patients who may
require hospitalization in intensive care 26.
In our study, it was observed that the laboratory parameters examined in
hospitalization such as NLR, LDH, prothrombin time, CRP, PaO2/FiO2,
D-Dimer, ferritin and fibrinogen levels were higher in severe patients
in line with previous studies conducted in patients with COVID-19. It
was also observed that the KIM-1 level taken care of during
hospitalization was high compared to moderately ill patients compared to
severely ill patients. This can be assessed as the KIM-1, which mediates
the endocytology of the virus in the cell, increases viremia.
In addition, increased viremia may have led to the development of MAS
with abnormal cytokine discharge in these patients later on. In the
evaluation of suPAR levels, we obtained a different observation with
previous studies. Compared to the healthy control group, it was observed
that the rising suPAR level in both moderate and severe COVID-19
patients was lower in severely ill patients than in moderate COVID-19
patients. SuPAR, which plays an important role in the migration of cells
involved in body defense, can be evaluated as aggravating the disease
due to the inability to create a low level adequate immune response in
severe patients. In addition, the decreased level of this molecule,
which plays a role in fibrinolytic activity, may have led to
hypofibrinolytic activity, causing acute respiratory distress.
The most important limit observed in our study was that the number of
our severely ill patients was small compared to the number of moderately
ill patients. However, due to the effects of the level of parameters
subject to our research on comorbidities, the exclusion of these
patients caused our number to be small.
As a result, KIM-1/TIM-1 acts as an important gateway to the entry of
the virus into the cell and its increased level of severely ill patients
seems to confirm this. Treatments for this gateway can play an important
role in treatment in COVID-19. In addition, the falling level of suPAR,
which plays a role in body defense and fibrinolisis, with the weight of
the disease may be the cause of parenchymal fibrosis development in
patients, increased predisposition to thromboembolic events and
increased virulence. This issue seems to need to be confirmed through
more extensive research.