Discussion
In our study, we found that procalcitonin and lactate levels were higher
in patients with severe CCHF when compared to patients with mild and
moderate CCHF. In the differentiation of severely ill patients from
mild/moderately ill patients, a lactate cut-off value of 1.9 mmol/L had
77.8% sensitivity and 76.9% specificity, whereas a procalcitonin
cut-off value of 0.61 ng/mol had 83.3% sensitivity and 89.7%
specificity. Both procalcitonin and lactate levels were positively
correlated with AST and ALT, which are frequently used parameters in
CCHF follow-up.
As in all viral hemorrhagic fevers, the basis of CCHF pathogenesis is
viral infection of various cell types, primarily endothelial cells,
mononuclear cells, and hepatocytes, followed by proliferation and
systematic spread 11. Increased endothelial
permeability and consequent endothelial damage is the main pathogenetic
process leading to death. This endothelial damage has been attributed to
two main mechanisms. The first is a direct viral effect on the
endothelial cells, and the second is damage caused indirectly by the
cytokines secreted from infected tissues 9,12,13.
The most important of these cytokines are tumor necrosis factor alpha,
interleukin (IL)-1, and IL-6, which are synthesized by type 1 helper T
cells and are involved in monocyte activation. The activation of
monocytes by cytokines impairs platelet activation and degranulation and
leads to an abnormal coagulation cascade in CCHF. Monocyte activation is
considered one of the main causes of hemophagocytic lymphohistiocytosis,
which leads to cytopenia and liver dysfunction in CCHF. Serum AST, ALT,
LDH, and creatine kinase (CK) are liver function indicators that are
frequently used parameters in clinical follow-up and have been
associated with poor prognosis 14-16.
Serum lactate level is another parameter frequently used in the clinical
practice, and although it may increase secondary to tissue
hypoperfusion, elevation may also occur due to causes unrelated to
hypoperfusion 17. Lactate, which can be synthesized in
many of the body’s tissues, is eliminated primarily by the liver and to
a lesser extent by the kidneys. A substantial proportion of studies
evaluating the relationship between lactate level and clinical course
and prognosis have observed that hypoperfusion increases lactate level
due to sepsis and septic shock 18. Our literature
search yielded no studies in which lactate level was associated with the
clinical course of CCHF. In the present study, serum lactate level was
found to increase in correlation with clinical severity in CCHF
patients. This may be attributed to the inadequate elimination of
lactate by the liver in CCHF, as liver dysfunction due to hemophagocytic
lymphohistiocytosis plays an important role in the clinical course of
this condition. Moreover, the increased cytokine levels seen in CCHF due
to the indirect effect of the virus might have led to muscle dysfunction
and higher levels of creatine kinase as well as lactate. This is
corroborated by the fact that muscle and joint pain are among the most
common presenting symptoms.
High serum procalcitonin level is often observed in bacterial infections
rather than viral infections. However, it has been found that increased
cytokine levels also increase amount of procalcitonin synthesized by
thyroid C cells in viral infections, independent of bacterial
superinfections 8,19. Procalcitonin level was reported
to be higher in patients with fatal CCHF and correlated with CRP level,
which is frequently used in routine practice 20. None
of the patients in our study died after clinical follow-up, and in line
with previous studies, we also found that procalcitonin levels were
higher in severely ill patients. This level also correlated with liver
function markers and serum lactate level. The lack of growth in blood,
urine, and sputum cultures performed after the increase in procalcitonin
levels suggest that this was due to high cytokine level.
The main limitation of our study was the inability to detect an
association between lactate and procalcitonin levels and mortality. This
was primarily due to the fact that during the study period, our hospital
was designated as a COVID-19 pandemic hospital during the pandemic, and
as a result there was a sharp decline in the number of patients we
followed due to CCHF in our hospital.