DISCUSSION
In this study, we analyzed the factors affecting ICU hospitalization and mortality in patients with Covid-19 and we determined that age older than 65 years, higher serum D-dimer, creatinine, and GGT levels than the upper limits of the laboratory at admission were independent factors predicting ICU hospitalization and mortality in COVID-19 patients. Moreover, in ROC analysis, we determined that GGT values higher than 30 U/l at admission should be regarded as a risk factor for mortality and these patients should be evaluated more intensely.
Since an early identification and timely intervention of patients with a tendency to become severe is essential to improve outcomes in COVID -19 patients, there are many studies in previous literature evaluating the predictive factors of outcomes. Jinrui et al. reported that the higher level of CRP and ALT levels and chronic comorbidities were the risk factors for the progression into severe pneumonia in COVID-19 patients12. Ullah et al. defined elevated CRP and D-dimer levels as independent predictors of in-hospital mortality13. Supporting our results, in a meta-analysis, age, and CRP levels were also defined as the main risk factors in predicting severe COVID-19 outcomes 14. Unlike this study, in our study, it was determined that GGT is important in predicting the outcome. Our strict exclusion criteria and the fact that the study was conducted in a larger population may explain this difference between these two studies.
Based on the admission data, in elderly patients, serum albumin and D-dimer levels and onset to hospitalization time were reported as significant predictors for the severity of COVID-1915. In another meta-analysis performed to identify the predictors associated with poor clinical outcomes in patients with COVID-19, severe COVID-19 was associated with lower levels of lymphocytes and hemoglobin; elevated levels of ALT, AST, creatinine, high-sensitivity CRP, D-dimer, ferritin, and LDH levels16. Our results were supporting these previous findings and we also determined that older age and elevated serum d-dimer, creatinine, and GGT levels at admission were independent factors predicting ICU hospitalization and mortality in COVID-19 patients. Admission serum CRP levels were associated with the ICU hospitalization but not with the mortality in our study. This may be associated with the late elevation of CRP levels requiring time for the synthesis during the hospitalization of patients.
In previous literature, patients with elevated liver function tests were related to more severe disease in COVID-19 8, 9. However, Ramachandran et al. reported that elevated AST or ALT levels among hospitalized COVID-19 patients were associated with higher rates of mechanical ventilation but were not a significant independent predictor of more severe disease 17. In a recent study from Turkey, elevated serum ALT, AST levels, and AST/ALT ratio >1 were associated with the more severe course and increased mortality in COVID-19 18. However, Ponziani et al. reported that baseline liver test abnormalities were associated with the increased risk of ICU admission but not the outcomes19. Similarly, Monterde et al. reported that abnormalities in liver function tests on admission were not associated with survival but with respiratory complications at admission. However, an increase during hospitalization in GGT, and ALP levels was associated with reduced survival 20. On the other hand, Zhang et al did not determine any role of ALT, AST, or GGT levels in predicting severe COVID-19 infection 21.
In a clinical epidemiological study, Shao et al reported that elevated GGT and CRP levels were associated with a longer length of hospital stay22. Very recently, abnormal liver biochemical tests at admission were reported to be closely related to the severity and prognosis of COVID-19 patients, supporting our findings23. In this study, we determined that elevated serum GGT levels, but not aminotransferases, at admission were associated with the increased risk for ICU hospitalization and mortality.
There are some limitations to this study that should be mentioned. First, this is a retrospective study carrying some bias of this type of investigation. Secondly, we did not analyze the effects of comorbidities in this group of patients, which may also affect the outcomes. Although we could not exclude all factors that may cause GGT elevation in participants, multicentered design of study and using same treatment algorithms were the strong ways of this current research.
In conclusion, in hospitalized patients with COVID-19, laboratory data on admission, including serum GGT, creatine, and d-dimer levels have an important predictive role for the ICU requirement and mortality. Since these tests are readily available in all hospitals and inexpensive, some predictive formulas may be calculated with these parameters at admission, to define the patients requiring more intense treatments.
Conflict of interest : None