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Advanced Neurology                                 Cerebrovascular pathology biomarkers in post-COVID-19 patients



                                                               in  Table  2.  It  is  worth  noting  that  in  the  comparison
                                                               group,  the  concentration  of  IL-6 both before  and  after
                                                               treatment was lower in women than in men. Previous
                                                               studies have shown that male gender is a risk factor for
                                                               more severe disease, with correspondingly higher serum
                                                               levels  of  IL-6  in  patients  with  COVID-19. 17,18   Multiple
                                                               genes associated with immune functions are situated
                                                               on the X chromosome; therefore, X-linked mosaicism
            Figure 3. Vascular endothelial growth factor A (VEGF-A) levels in blood   confers a highly polymorphic genetic expression, enabling
            serum in patients who had contracted COVID-19 1 – 1.5 years earlier,   females to respond with a more expanded immunological
            before and after treatment                         repertoire than men.  Nevertheless, in our study, no
                                                                                 19
                 a
            Notes:  P  <  0.05 when comparing the serum VEGF-A levels of the   gender differences in the concentration of IL-6 were found
            experimental group and the comparison group before treatment;  P < 0.05   in the experimental group.
                                                     b
            when comparing the serum VEGF-A levels of the experimental group
                             t
            after and before treatment; P < 0.05 when comparing the serum IL-6 levels   In women in the experimental group, the concentration
            of the experimental group and the comparison group after treatment.  of ET-1 in the blood serum was lower than the corresponding
                                                               indicator in men, but only before treatment. The obtained
              Therefore, SARS-CoV-2 leaves its mark not only in
            the form of cytokine load but also in the activation of   data does not contradict the conclusions of previous
                                                               studies that reported more severe endothelial dysfunction
            the  endothelial  system,  facilitating the  development  of   in men with COVID-19. 20,21  Overall, pretreatment serum
            endothelial dysfunction. This endothelial dysfunction is   levels of IL-6, ET-1, and VEGF-A in both male and female
            evidenced by the established two-to-threefold increase   COVID-19 survivors were higher than those of male and
            in the levels of ET-1 and VEGF-A in the blood serum of   female comparison group patients.
            patients who had COVID-19.
                                                                 After treatment, the concentration of IL-6 in the blood
              Changes in VEGF levels have been described during
            both bacterial and viral infections.  Human viruses   serum  of  men  in  the  experimental  group  decreased,
                                           15
                                                               while it did not change in the women. Similar changes
            may  upregulate  the  expression  of  VEGF  directly  or   were recorded in the comparison group. The level of
            indirectly through various mechanisms involving HIF-1α,   ET-1 after treatment significantly decreased in men of
            cyclooxygenase 2, activator protein-1, NF-κB, and IL-6.    the comparison group but did not change in women.
                                                         16
            Importantly,  the  release of VEGF in response  to  viral   Conversely, in the experimental group, there were no
            infection does not occur as an isolated event but is part of a   changes in men, whereas this indicator of endothelial
            molecular network characterized by concomitant increases   dysfunction decreased in women. For the concentration of
            of proinflammatory systemic cytokines or chemokines such   VEGF-A in the blood serum of both groups, there were no
            as IL-6, IL-8, and monocyte chemoattractant protein-1,   gender differences after treatment.
            or imbalances in leukocyte subsets. Therefore, the
            overproduction of VEGF appears as a common feature of   3.3. Severity of COVID-19 infection and vaccination
            infections or inflammation and is not specific to COVID-19.
                                                               Figure  4 illustrates the indicators of the biomarkers of
              The 2-week treatment of patients in both groups had   patients in the experimental group, categorized by the
            different  effects  on the  biomarkers  studied.  Specifically,   severity  (mild,  moderate,  or  severe)  of  COVID-19  they
            IL-6 levels in the experimental group did not decrease after   experienced 1 – 1.5 years ago.
            treatment and remained significantly higher compared to
            the comparison group (Figure 1). However, the treatment   Notably, there were no differences in IL-6 concentrations,
            was more effective in the comparison group, leading to a   whereas ET-1 and VEGF-A differed significantly between the
            decrease in the IL-6 level. Notably, the treatment had no   severity levels of COVID-19. Significantly, mild COVID-19
            effect on the ET-1 levels in the blood serum of either group   infection had the most significant impact on the endothelial
            (Figure 2). In contrast, the serum concentration of VEGF-A   system, as evidenced by increased levels of these biomarkers
            in patients of both groups decreased almost twofold due to   compared to the values in moderate and severe infections. It
            treatment (Figure 3), leading to the normalization of this   was observed that during the treatment for CVD in patients
            indicator in patients in the experimental group.   with a mild COVID-19 infection 1 – 1.5 years earlier, there
                                                               was no normalization of endothelial dysfunction.
            3.2. Gender characteristics                          Previous studies have shown that in patients with
            Gender characteristics in the serum biomarker levels of   a history of COVID-19 of varying severity, there is an
            inflammation and endothelial dysfunction are presented   increase in the expression of VEGF-R2, which may


            Volume 3 Issue 2 (2024)                         4                                doi: 10.36922/an.2878
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