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.