Discussion
The COVID-19 disease caused by SARS-CoV-2 continues to show its effects
despite the increased use of antiviral treatments and vaccination. In
this study, we aimed to develop markers that can be used to predict
mortality through laboratory parameters. Studies have reported close to
100% mortality among patients requiring mechanical ventilation (4). Our
study is even more important since we observed that our mortality rate
was 60.4% in our 1-year intensive care follow-up. In our study, the
mortality rate was found to be high in intubated patients; the
difference was statistically significant.
If we look at the gender-mortality relationship, the M/F ratio was 1.28
in our study. An in-depth study examining Covid19 effect on Italy, on
123.3 thousand coronavirus deaths, revealed that the fatality rate was
much higher for the male gender. If the mortality rate for female
patients was 2.5 percent, the corresponding figure for male patients was
3.4 percent. However, the COVID-19 case fatality rate is higher in women
than men in a few countries, such as India, one of the worst-affected
countries. As of Sept 30, 2020, India had more than 6·4 million recorded
COVID-19 cases (5). In India, the COVID-19 case fatality rate among men
is 2·9% and 3·3% among women (6). Both group 1 and group 2
patients had comorbid diseases, but the presence of comorbid disease was
not significant between the two groups.
When laboratory parameters were examined, procalcitonin, CRP, BUN,
D-dimer, troponin, LDH, lactate, high INR, and low albumin were
statistically significant in terms of mortality. As a result of logistic
regression analysis, low PLT and high D-dimer were determined as
independent variables for mortality. In the study conducted by Fan et
al. (7), lymphopenia and increased lactate dehydrogenase (LDH) values
were associated with higher ICU admission rates. Patients transferred to
the ICU had lower lymphocyte counts, lowest monocyte counts, and lowest
hemoglobin and higher peak Neutrophil (NEU) counts, and highest LDH
levels compared to patients who did not require an ICU stay. Similarly,
in SARS disease, high CRP levels, lymphopenia, leukopenia, and elevated
aminotransferase, LDH, and creatine kinase levels have been shown in
most patients (8). Liver dysfunction is observed more frequently in
severe cases of COVID-19 than in those with milder severity, and an
increase in Alanine aminotransferase (ALT), aspartate aminotransferase
(AST), and total bilirubin levels have been observed in many ICU
patients (9). Infection of liver cells with SARS-CoV-2 cannot be
excluded as 2-10% of patients with COVID-19 have diarrhea, and viral
RNA is detected in both stool and blood samples, suggesting the
possibility of hepatic virus presence (10). High C-reactive protein
(CRP), ferritin and lactate dehydrogenase (LDH) levels were found to be
correlated with the severity of the disease and prognosis (11,12).
In the study of Wang D et al. (13), the ability of procalcitonin
elevation to predict 28-day intensive care mortality was found to be
statistically significant.
In the study of Mardani et al. (14), in which they examined 200 patients
in a single-center, they reported that ALT, CRP, NEU, LDH, and BUN
values had extreme accuracy in predicting PCR positive patients. In the
same study, low WBC and lymphocyte counts were evident in PCR-positive
patients, but we could not find a significant difference between the
patients with a mortal course and the living group in our study.
In the study of Zhao et al. (15), the most common laboratory findings in
COVID-19 patients were decreased lymphocyte count, prolonged APTT,
elevated LDH, CRP, and erythrocyte sedimentation rate (ESR). Erol et al.
(16) examined 101 patients and showed that CRP, LDH, D-Dimer values were
significantly higher, and WBC values were significantly lower in the
patient group who died. In our study, similar to these results, we found
high CRP, D-Dimer LDH values in the patient group who died. Although low
platelet levels did not make a significant difference between the groups
in the study of Erol et al., platelet levels were significantly lower in
the deceased group in our study. In the study of Deng et al. (17),
increased leukocyte count and decreased lymphocyte count in the survival
group were associated with mortality. Our study did not observe
significant differences in leukocyte counts and lymphocyte counts in
both groups.
The predictive value of LDH as an indicator of altered glucose
metabolism in patients with sepsis is known (18). In the study conducted
by Gao et al. (19), laboratory parameters such as ALT, CRP, AST, and LDH
can be used to predict the presence of disease. Tsui et al. (20)
examined 323 cases with severe acute respiratory failure and stated that
high LDH level was an important prognostic factor. Similarly, we found
that LDH levels were significantly higher in the mortality group in our
study.
In our study, we concluded that D-dimer elevation is an independent
variable for mortality. Similarly, according to a report published in
Wuhan, patients with D-dimer levels of 2.0 ng/mL had a higher mortality
rate than patients below 2.0 ng/mL (21).
In a meta-analysis including 25 studies published by Huang et al. and
5350 patients in total, high levels of CRP, procalcitonin, D-dimer, and
ferritin were associated with poor outcomes (22). COVID-19 infection
manifests with a coagulopathy problem characterized by procoagulant
factors such as fibrinogen and predominantly high D-dimer levels,
increasing mortality. In our study, fibrinogen levels were high in both
groups, and the difference was not statistically significant. Likewise,
although ferritin values were higher in the mortality group in our
study, we could not find a significant difference between the two
groups. However, we believe that high ferritin levels are associated
with the hyperinflammatory state.
In a meta-analysis of 11 studies and 910 patients reviewed by Aziz et
al., a correlation was shown between hypoalbuminemia and severe
COVID-19, and it was reported that it would facilitate the early
diagnosis of severe disease and help clinicians (23). In our study, we
found that hypoalbuminemia was statistically significant in the
mortality group.
Similarly, in the study of Erol et al. (16), AST values were higher in
non-survivors compared to survivors, and there was no difference in more
specific ALT values in the liver. In our study, the AST value was higher
in the mortality group, and the difference was not statistically
significant (p=0.001). Zhang et al. (9) showed that 2-11% of COVID-19
patients have liver comorbidity and 14-53% of cases have abnormal ALT
and AST levels during COVID-19 disease progression. Thus, liver damage
appears to be more common in severe cases compared to mild cases of
COVID-19. Yang et al. (24) found no difference in the incidence of
abnormal liver function between survivors (30%) and non-survivors
(28%).
The limitation of our study is that it is retrospective, the number of
patients is small, and it is single-centered. In conclusion, full
treatment has not been provided yet in the Covid-19 pandemic, which has
left its mark on the last century and has caused many deaths.
Vaccination and vaccine development studies continue. Nevertheless, we
think that the high procalcitonin and D-dimer values obtained with this
study, which was carried out with the markers in the rapid and easily
accessible blood tests routinely examined in Covid-19 patients, may
contribute to the prediction of mortality.