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