Эндотелиальная дисфункция сосудов как возможный предиктор тяжелого течения COVID-19

Abstract

Objective. To study the role of the main marker of endothelial dysfunction VEGF-A as a possible predictor of severe COVID-19 formation. Patients and methods. On the basis of the clinic of the Republican Specialized Scientific and Practical Medical Center of Epidemiology, Microbiology, Infectious and Parasitic Diseases (RSSPMCEMIPD) and Samarkand Regional Specialized Medical Center, 210 patients with coronavirus infection were examined during 2020–2022. Patients were divided into 2 groups comparable by main characteristics: I consisted of 98 (47%) patients with a moderate form of COVID-19, II – 112 (53%) with a severe form of the disease. All patients were fully examined at admission to the hospital and at discharge from it. The level of medium molecular peptides (MMP) in blood plasma was determined by the method of N.I.Gabrielyan on spectrophotometer SF-46 in ultraviolet spectrum; the levels of vascular endothelial growth factor (VEGF-A) – in 163 patients – and interleukins 1 and 6 (IL-1, IL-6) in blood serum – by enzyme immunoassay (test systems of Cytokin LLC and Vector-Best JSC). The level of C-reactive protein (CRP) was determined using the immunoenzyme analyzer "MINDRAY MR-96A"; procalcitonin and D-dimer values were determined using an automatic ELISA analyzer mini-VIDAS. The obtained results were processed by methods of descriptive and variation statistics. Differences were considered reliable at (p < 0.05). Results. The clinical picture of COVID-19 complicated by pneumonia was characterized by pronounced symptoms of intoxication, respiratory tract damage, respiratory failure. In group II patients, such comorbidities as ischemic heart disease (23.5 vs. 41.1%), arterial hypertension (9.2 vs. 25.4%), and diabetes mellitus (2.0 vs. 12.5%) were recorded significantly more often. In 119 (56.7%) cases (mostly in the group with severe coronavirus infection), there was a combination of several comorbidities. In 36 (17.1%) patients with elevated blood sugar level before hospitalization for COVID-19 neither clinical nor laboratory signs of diabetes ellitus were present; in group II stable elevated blood sugar level against the background of therapy of the main disease was recorded 2 times more often (23.2 vs. 10.2%, respectively). In the same group, the level of CPR was 1.5 times higher. A significant correlation (p < 0.05) of elevated levels of CRP and D-dimer with the severity of COVID-19 course was established. In 163 patients the mean values of VEGF-A on admission were elevated; in patients from group II this index was significantly (p < 0.01) higher: 303.02 ± 21.47 vs. 390.52 ± 29.05 pg/mL. At discharge, this index increased to 466.56 ± 37.59 pg/mL in group II patients and decreased to 237.60 ± 17.03 pg/mL in group I patients (differences were significant; p < 0.01). In group I, this index returned to normal after 1 month, and in group II, it decreased to 205.05 ± 15.90 pg/mL only 2 months after discharge. A reliable correlation (p < 0.05) of elevated levels of D-dimer, CRP, MMP with high VEGF-A levels, as well as with the severity of the disease and increasing respiratory failure was established. Positive results of bacteriologic study of upper respiratory tract secretions were found in 63 (64.3%) patients of group I and in 78 (69.6%) patients of group II; Staphylococcus aureus predominated in patients from group II (11.1 vs. 38.5%) and Candida spp (85.7 vs. 28.2%) from group I. Conclusion. The relationship between blood levels of VEGF-A and standard inflammatory markers allows us to propose this factor of endothelial dysfunction as a predictor of inflammation and disease progression, as well as to use it to assess the efficacy of therapy. Key words: bacterial pneumonia, novel coronavirus infection, procalcitonin, C-reactive protein, vascular endothelial growth factor, endothelial dysfunction