[Effect of anticoagulant therapy on the course of COVID-19 in comorbid patients].

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.

Human cytomegalovirus-IgM seropositivity is not associated with atherogenic alterations of lipid profiles and inflammatory status in ischemic stroke patients: a preliminary study.

BACKGROUND: Past exposure to human cytomegalovirus has been suggested to participate in the pathogenetic events associated with atherosclerotic lesion establishment and progression. However, whether ongoing human cytomegalovirus infection is related to plaque instability, and subsequent acute cerebral ischemia, is relatively unknown. The purpose of this study was to evaluate the potential relationships between active human cytomegalovirus infection and ischemic stroke, especially in regard to metabolism and inflammation. METHODS: Ninety-nine acute ischemic stroke patients, associated with large artery atherosclerosis, were divided into two groups based on the presence or absence of human cytomegalovirus immunoglobulin M (IgM) (human cytomegalovirus-IgM-positive/human cytomegalovirus-IgM-negative = 33:66). Baseline clinical characteristics, inflammatory factors, and biochemical assessments were compared in both groups. Then, all patients and human cytomegalovirus-IgM-positive patients were divided into quartiles according to their high-sensitivity C-reactive protein levels, respectively, and risk factors were compared. Finally, correlations between inflammatory factors (high-sensitivity C-reactive protein and white blood cell count) and other atherosclerosis risk factors in both human cytomegalovirus-IgM-positive and -negative subjects were evaluated. RESULTS: An association between human cytomegalovirus-IgM seropositivity and atherogenic modification of metabolism and inflammatory status were not found in this study. Both age and white blood cell count increased across quartiles of high-sensitivity C-reactive protein in all subjects (P = 0.001), while age and low-density lipoprotein cholesterol increased across quartiles of high-sensitivity C-reactive protein in the human cytomegalovirus-IgM-positive group (P = 0.02 and 0.007, respectively). Multivariate linear regression analysis showed that high-sensitivity C-reactive protein was associated with age in human cytomegalovirus-IgM-positive group (P = 0.002), while no other factor was associated with white blood cell count in these subjects. CONCLUSION: Our study provided no evidence for the direct implication of active systemic human cytomegalovirus infection, represented by human cytomegalovirus-IgM positivity, in the pathogenesis of acute ischemic strokes, particularly those involving plaque instability and metabolic disorders.

[Expression of human cytomegalovirus immediate early gene in the intracranial artery walls of atherosclerosis].

OBJECTIVE: Human cytomegalovirus (HCMV), especially the immediate early (IE) gene of the virus, has been implicated in the pathogenesis of atherosclerosis. The aim of this study was to confirm the presence of HCMV IE gene DNA in intracranial artery walls and the association of the virus with the development of atherosclerosis. METHODS: HCMV IE gene was tested in formaldehyde-fixed intracranial arteries from 35 cases with cerebral atherosclerosis and 20 negative controls. In situ hybridization as well as polymerase chain reaction (PCR) was used to detect the presence of DNA in sections of paraffin-embedded tissue samples. Probes and primers were derived from major immediate early (MIE) genomic regions of cytomegalovirus strain AD169. RESULTS: The DNA of HCMV was found in 40.0% and 10.0% of arterial walls with atherosclerosis and negative control group by in situ hybridization, respectively, in 60.0% and 30.0% by PCR, respectively. Significant deference was found between them (P=0.018, P=0.032). There was also significant difference between grade III-IV and grade I-II atherosclerosis by both methods (P=0.027, P=0.009). CONCLUSION: The results suggested that HCMV IE DNA exists in the atherosclerotic arterial walls, therefore, there might be an association between the IE gene in intracranial artery walls and the atherosclerosis. The arterial wall with the smooth muscle cells, might be the potential site of the virus persistence. HCMV may play a role in the pathogenesis of the atherosclerosis.

The contribution of inducible nitric oxide and cytomegalovirus to the stability of complex carotid plaque.

BACKGROUND: Although the association between inflammation and atherosclerosis is well established, the biologic events that trigger the local inflammatory response within plaque are not fully understood. Cytotoxic free radicals and infectious agents, both of which are associated with an inflammatory response, have previously been implicated in the initiation and progression of atherosclerosis. In this study, we analyzed carotid plaque for evidence of oxidative vascular injury by determining the presence and distribution of inducible nitric oxide synthase (iNOS) expression and nitrotyrosine formation and for evidence of infection with cytomegalovirus. METHODS: Carotid plaque from 51 patients who underwent endarterectomy for either primary (n = 37) or recurrent (n = 14) stenosis were examined histologically (hematoxylin-eosin staining and Masson's trichrome staining) and with immunohistochemistry with specific antibodies to alpha-smooth muscle actin, macrophages (CD68), T-lymphocytes (CD3), and T-cell activation (human leukocyte antigen-DR). Twenty-eight specimens from patients with primary (n = 15) and recurrent (n = 13) stenosis were examined for the presence of iNOS and nitrotyrosine with immunohistochemistry and in situ hybridization (iNOS). Twenty-three additional specimens (22 primary, and 1 recurrent) were analyzed with antibodies to p53, cytomegalovirus, and the polymerase chain reaction (cytomegalovirus, n = 8). RESULTS: Primary atherosclerotic lesions were either complex heterogenous cellular plaques (n = 29) or relatively acellular fibrous plaques (n = 8). Ten of 14 recurrent plaques were either complex or fibrous lesions, and the remaining four were typical of myointimal thickening. CD68-positive staining cells were detected in all specimens regardless of their structural morphology. CD3-positive cells were interspersed between macrophages in all heterogeneous cellular plaques and only infrequently noted in fibrous plaques. iNOS and nitrotyrosine immunoreactivity were detected in macrophages and smooth muscle cells in all complex and fibrous plaques and in two of four myointimal plaques. The presence of iNOS and nitrotyrosine in plaque correlated with the existence of symptoms in 80% of primary and 62% of recurrent lesions. Cytomegalovirus was detected in only two of 23 carotid specimens (9%). CONCLUSION: The association between ischemic cerebrovascular symptoms and iNOS and nitrotyrosine immunoreactivity in complex primary and recurrent carotid plaque and the infrequent occurrence of cytomegalovirus in primary carotid lesions suggests that ongoing free radical oxidative damage rather than viral infection may contribute to plaque instability in patients with complex and fibrous carotid plaques.