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.