Discussion
In the present study, to our knowledge, for the first time we have measured MK levels in consecutive COVID-19 patients. There was no significant difference found between mortal and survival groups with respect to serum MK levels in followed patients. At the same time, it was determined that serum MK value did not have a significant importance in predicting mortality due to COVID-19 disease. Since COVID-19 disease mainly affects respiratory and immune systems, respiratory epithelial cells and immune T lymphocytes appear to be clear targets for COVID-19 disease.15-19 MK occurs in varying concentrations in the skin and major respiratory tract, against potential pathogens which the body encounters for the first time. This protein is a growth factor which its function has been investigated in many healthy volunteers, some bacterial or viral infections and serious conditions such as sepsis.15,16,20,21 The serum levels of MK in healthy individuals are ranged from 302 to 1068 pg/mL.20 In the in vitro studies, the researchers found that MK had a strong bactericidal activity against the respiratory pathogen Streptococcus pneumoniae and Escherichia coli but no activity against Staphylococcus aureus.22,23 Also, it’s a cytokine that inhibits HIV infection in an autocrine and paracrine manner by preventing the adherence of HIV particles when added to CD4 cells before HIV virus, but it has no significant effect when added after virus entry to the T lymphocyte.17 In our study population, we measured MK values within normal limits in mortal and non-mortal patients. A significant sensitivity and specificity could not be reached as a result of the ROC analysis performed to establish a certain cut-off value. These results may indicate that COVID-19 disease suggests that unlike some viruses, it can enter the cell without using MK protein and causes immunopathological damage. However, this data needs to be verified with different methods.
Recent studies showed that MK has a new role in acute and chronic inflammatory diseases including colitis, atherosclerosis, multiple sclerosis, nephritis, and rheumatoid arthritis have been shown to be alleviated in the absence of MK in animal models.24These chronic inflamatuar diseases critically affect patients’ quality of life. For instance; in cases of atherosclerosis, when endothelial dysfunction develops, MK excessively expresses and causes leukocyte infiltration in the damaged area. In animal study, it has been shown that MK-deficient mice did not increase leukocyte infiltration.25 It has been shown to cause fatal thrombotic microangiopathies as a result of hyperinflammation occurring secondary to COVID-19 disease. COVID-19 virus invading the endothelium with its ACE2 receptor causes severe endothelial damage and degradation in endothelial cell membranes.26,27 Despite this, although our study population accompanied chronic diseases such as diabetes mellitus and hypertension, we did not find any significant relationship between MK levels and mortality. Perhaps, MK’s may have a more meaningful function in the chronic inflammation process rather than in acute inflammation. Also, we investigated the levels of MK only as soon as patients were hospitalized. Maybe if we had taken several MK measurements at different stages of the disease during hospitalization, we would have reached a more accurate result.
Many acute phase reactants and proinflammatory cytokines have been identified as determining factors in mortality from COVID-19 disease.18 In our study, we think that the increased serum values of these indicators of mortality in COVID-19 patients was in accordance with the literature supporting the reliability of the patient population and the results of the study for MK.
A small number of patients and the shorter observation period are among the limitations of our study. In addition, plasma MK levels were measured only once at admission and were not continuously monitored; therefore, trends in plasma MK levels in survivors and non-survivors are unknown. We think that MK should be studied in subgroups such as patients with bacterial superinfection.
In conclusion, MK is not a biomarker that can reinforce known predictors of mortality in COVID-19 patients and can provide better predictions of mortality. Nethertheless, COVID-19 is a self-limited infection, in which the strength of the host’s immune strength plays a significant role against it in the common patients [28]. It can be said that the MK can help this self-limited infection due to its antiviral feature. This assumption should be confirmed by in vitro and in vivo studies of COVID-19.
Acknowledgments: We would like to thank the Sakarya Training and Research Hospital and the Infection Control Committee for their support in this research.
Conflict of Interest: The authors declare that they have no conflict of interest.
Funding information: This work has not received any funding