Discussion
In this study, it was seen that low neutrophil count and MPV level, high
platelet count and ferritin levels may be important monitoring
parameters in the course and follow-up of COVID-19 infection. Besides,
in our study, it was found that the laboratory levels of infection came
up with important results affecting the duration of hospitalization.
As part of various studies on COVID-19 disease, it has been reported
that the duration of hospitalization may be prolonged due to comorbidity
conditions (obesity, diabetes, hypertension, and coronary heart
disease), lymphopenia, high D-dimer and ferritin levels (11-13).
However, studies on clinical and laboratory parameters that can
determine the prognosis of patients are limited. As far as we know,
there is no comprehensive study on prognostic factors affecting the
duration of hospitalization in COVID-19 patients.
In our study, the mean hospitalization period of the patients was 7.2 ±
4.1 days. In correlation analysis between duration of hospitalization
and laboratory parameters, a positive correlation was found between the
duration of hospitalization and the 1st and 5th day NLR, CRP,
procalcitonin, D-dimer, fibrinogen, the 5th day PLR, and ferritin
levels. The low course of lymphocyte count both at admission and
follow-up was seen to be the most important factor in prolonging the
length of the duration of hospitalization. Therefore, it was observed
that these parameters are factors affecting the duration of
hospitalization in the follow-up of infection for COVID-19 patients in
accordance with the literature.
It was reported as a result of a meta-analysis on COVID-19 patients that
the male gender was predominant at a rate of 60%, and the male gender
at a rate of 63% with an average age of 46.4 was predominant in another
study (12,13). In our study, the mean age and male gender predominance
of our patients were consistent with that of the literature.
As part of a study investigating the clinical characteristics of
COVID-19 patients, 64.5% lymphopenia, and 29.4% leukopenia were found
(12). In a study by Fu et al., 45.3% lymphopenia, 21.3% leukopenia,
and 12% thrombocytopenia were found (7). In a study examining the
laboratory parameters of 3377 patients, there was observed a slight
increase in the WBC count in patients with severe disease, while there
was a clinically significant increase in this parameter in patients who
died (5). Therefore, in patients with severe disease, a significant
increase in WBC may indicate clinical worsening and an increased risk of
poor outcomes. Lymphopenia is a common feature in these patients, and a
decrease is observed in the percentages of monocytes, eosinophils, and
basophil cell percentages as well as CD4/CD8 T cells and natural killer
cells (1,5,14). It has been suggested that survival with COVID-19 may
depend on its ability to regenerate lymphocytes killed by the virus.
Therefore, the lymphocyte count, especially CD4, can be used as a
clinical predictor of severity and prognosis (14). In our study, while
the WBC and lymphocyte count were statistically lower in the patient
group at the time of admission compared to the control group, no
significant difference was found between the two groups in terms of
neutrophil count. It was seen that neutrophil count was lower and there
was no significant difference in the WBC and lymphocyte count on the 5th
day of the follow-up of the patients compared to the time of admission.
This indicates that COVID patients have lower WBC and lymphocyte count
compared to the normal population; however, there is no significant
change in the first 5 days of infection, and low levels of neutrophil
should be closely monitored during the follow-up of the disease.
Increased neutrophil count and the associated increase in NLR levels are
other findings observed in COVID-19 patients. It has been reported that
the neutrophil to lymphocytes ratio (NLR), which can be easily
calculated from a routine blood test by dividing the absolute neutrophil
count to the absolute number of lymphocytes, has a significant value in
demonstrating the general inflammatory status of a patient (6). In a
study, it was found that neutrophil rate was 51.6% and the increased
NLR level was associated with the severity of the disease, poor
prognosis, and duration of hospitalization (8). In our study, while the
NLR level was higher in the patient group compared to the control group
at the time of admission, there was no significant difference in the 1st
and 5th day NLR levels of the patients. In light of these results, we
believe that the NLR level may be important in the diagnosis of the
COVID-19 infection; however, it has no prognostic significance in the
follow-up of the disease.
Thrombocytes are immune cells that play an important role in the human
body. The incidence of thrombocytopenia in critically ill patients
admitted to the intensive care unit varies between 15-60% (5). In a
meta-analysis where the relationship between thrombocytopenia and
COVID-19 severity is investigated, low platelet count was found to
increase the risk of severe disease and mortality three times in
COVID-19 patients and prolonged the length of hospitalization (3).
According to another study, platelet peaks and increased PLR levels
observed in the follow-up of symptomatic and asymptomatic patients were
found to be associated with the severity of the disease and the duration
of hospitalization (8). The PLR level is calculated by dividing the
absolute platelet count by the absolute lymphocyte count. The high level
of PLR of the patients refers to the degree of cytokine storm that can
provide a new indicator in the follow-up of patients with COVID-19
(8,15).
Mean platelet volume (MPV) is a laboratory marker associated with
platelet function and activity. High MPV is hemostatically more reactive
and produces higher amounts of the prothrombotic factor, thromboxane.
This increased thromboxane causes thrombotic sensitivity and therefore
results in thrombotic complications (16). According to a study by
Elsayed and
Mohamed,
it was reported that increasing MPV and MPV/thrombocyte count ratio is
an important risk factor in the development of thromboembolic events
(17). In the study by Pan et al., the increased MPV level was found to
be a distinctive feature in COVID-19 patients (18). In our study, the
number of platelets at the time of admission was significantly lower,
while PLR and MPV levels were higher in the patient group compared to
the control group. It was found that the MPV level was lower and the
platelet count was higher on the 5th day of the patient follow-up
compared to the time of admission. We think that these results may be
associated with platelet levels increased by the improvement of
thrombocytopenia with the healing process in patients with initial
thrombocytopenia or by the progress of the disease in patients with
normal thrombocyte levels at the beginning. However, due to the lack of
sufficient and high level of evidence about this situation, we believe
that studies with a larger patient series should be carried out.
We think that the high MPV level in the early stage of the disease and
its low course in the follow-up may be related to the prognosis.
Therefore, the MPV level can be used as a good prognostic factor in the
follow-up of COVID-19 infection.
Ferritin that is used as an inflammation marker significantly increased
during the course of the disease in patients with severe COVID-19.
Therefore, serum ferritin levels should be used to monitor prognosis in
COVID-19 patients during hospitalization. The increase in the CRP level
with ferritin indicates the development of systemic inflammatory
response syndrome. The exaggerated elevation that may lead to cytokine
storm can lead to tissue damage progressing to acute lung injury and
multi-organ failure (19,20). In a study examining the relationship
between the severity of the COVID-19 disease and procalcitonin, a
significant difference was observed only in the procalcitonin level
between severe and non-severe forms of the disease. However, in another
study, an approximately five-fold higher risk of severe COVID-19
infection was observed in patients with increased procalcitonin (4,20).
D-dimer occurs due to the destruction of the fibrin clot formed by
cross-links by the plasmin with the activation of the coagulation system
for any reason (5). In a study by Zhang et al., comparing D-dimer levels
at the time of admission, it was stated that a high D-dimer level at the
time of admission was an important factor affecting mortality (21).
D-dimer is significantly elevated in patients with both severe and fatal
COVID-19 (5). In our study, significantly high levels of ferritin were
observed on the 5th day compared to the time of admission. However, no
significant difference was observed in CRP, procalcitonin, D-dimer, and
fibrinogen levels in prognostic terms. With these results, we think
that, instead of inflammatory markers such as CRP and procalcitonin and
thrombosis indicators such as D-dimer, the ferritin level should be
closely monitored to predict the severity of the infection.
Our study had limitations such as being retrospective performed in a
single center and a short study period, and not investigating other
inflammatory indicators such as lymphocyte subtypes and cytokines.