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Objective: S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are indicators of global transmethylation and may play an important role as markers of severity of COVID-19., Methods: The levels of plasma SAM and SAH were determined in patients admitted with COVID-19 ( n = 56, mean age = 61). Lung injury was identified by computed tomography (CT) in accordance with the CT0-4 classification., Results: SAM was found to be a potential marker of lung damage risk in COVID-19 patients (SAM > 80 nM; CT3,4 vs. CT 0-2: relative ratio (RR) was 3.0; p = 0.0029). SAM/SAH > 6.0 was also found to be a marker of lung injury (CT2-4 vs. CT0,1: RR = 3.47, p = 0.0004). There was a negative association between SAM and glutathione level ( ρ = -0.343, p = 0.011). Interleukin-6 (IL-6) levels were associated with SAM ( ρ = 0.44, p = 0.01) and SAH ( ρ = 0.534, p = 0.001) levels., Conclusions: A high SAM level and high methylation index are associated with the risk of lung injury in patients with COVID-19. The association of SAM with IL-6 and glutathione indicates an important role of transmethylation in the development of cytokine imbalance and oxidative stress in patients with COVID-19., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2021 Evgeny Vladimirovich Kryukov et al.)

Objective: Aminothiols (glutathione (GSH), cysteinylglycine (CG)) may play an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), but the possible association of these indicators with the severity of COVID-19 has not yet been investigated., Methods: The total content ( t ) and reduced forms ( r ) of aminothiols were determined in patients with COVID-19 ( n = 59) on admission. Lung injury was characterized by computed tomography (CT) findings in accordance with the CT0-4 classification., Results: Low tGSH level was associated with the risk of severe COVID-19 (tGSH ≤ 1.5  μ M, mild vs. moderate/severe: risk ratio (RR) = 3.09, p = 0.007) and degree of lung damage (tGSH ≤ 1.8  μ M, CT < 2 vs. CT ≥ 2: RR = 2.14, p = 0.0094). The rGSH level showed a negative association with D-dimer levels ( ρ = -0.599, p = 0.014). Low rCG level was also associated with the risk of lung damage (rCG ≤ 1.3  μ M, CT < 2 vs. CT ≥ 2: RR = 2.28, p = 0.001). Levels of rCG ( ρ = -0.339, p = 0.012) and especially tCG ( ρ = -0.551, p = 0.004) were negatively associated with platelet count. In addition, a significant relationship was found between the advanced oxidation protein product level and tGSH in patients with moderate or severe but not in patients with mild COVID-19., Conclusion: Thus, tGSH and rCG can be seen as potential markers for the risk of severe COVID-19. GSH appears to be an important factor to oxidative damage prevention as infection progresses. This suggests the potential clinical efficacy of correcting glutathione metabolism as an adjunct therapy for COVID-19., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2021 Evgeny Vladimirovich Kryukov et al.)

Aim: To analyze the systemic manifestations of vascular endothelial damage, the activation of hemostatic and inflammatory responses in patients with an infectious inflammation-dependent exacerbation of chronic obstructive pulmonary disease (COPD)., Subjects and Methods: The paper provides the data of examinations of 111 patients with the clinical signs of an infectious inflammation-dependent exacerbation of COPD who had 2 or 3 positive criteria elaborated by N. Anthonisen et al. (1987). The patients were divided into 2 phenotypically different subgroups: 1) 92 (82.9%) COPD patients without clinical manifestations of bronchoectasis; 2) 19 (17.1%) patients with COPD concurrent with documented bronchiectasis. The patient subgroups were matched for smoking status and the characteristics of COPD and respiratory failure. The investigators assessed the time course of changes in the serum level of endothelin-1 (ET-1), the aggregation function of platelets, and the plasma concentrations of D-dimers and homocysteine in patients with COPD compared to healthy, never smokers (n = 35) and smokers (n = 27)., Results: An increase in the levels of the endothelial dysfunction markers ET-1 and homocysteine was found in patients with COPD, which was comparable with the changes in these indicators in the group of smokers. In both subgroups, the rise in plasma D-dimer levels was more pronounced in the patients with a COPD exacerbation than in the smokers. Its therapy with systemic and inhaled glucocorticosteroids reduced C-reactive protein and ET-1 levels in both patient subgroups and in D-dimers in subgroup 1. Elevated D-dimer levels remained when achieving remission, which points to the risk of thrombogenic and thromboembolic events in the patients with an infectious inflammation-dependent exacerbation of COPD and concomitant circulatory system diseases., Conclusion: The patients with an infectious inflammation-dependent exacerbation of COPD are observed to have elevated peripheral blood markers of endothelial dysfunction and thrombinemia. These changes are pathogenetically caused by smoking or neutrophilic inflammation and associated with a higher risk of thrombogenic events.

Presented herein are the findings of examination of 176 people. Of these, 128 were found to suffer lower limb atherosclerosis (LLA) and 48 were apparently healthy people constituting a control group. Amongst the 128 patients, 74 (58%) had atherosclerotic lesions of the iliac arteries, 54 (42%) subjects had lesions of the femoral and popliteal arteries. The average age of the patients amounted to 62.4±4.3 years. There were ten (8%) women and 118 (92%) men. The control group consisted of 42 (89%) men and six (11%) women. The mean age of the control group patients was 58.9±3.2 years. All underwent functional and laboratory examinations including angiography, duplex scanning and dopplerography of lower limb arteries, as well as determining blood serum markers of inflammation (hs-CRP and IL-6), as well as endothelial lesion markers (ET-1 and VWF). The comparative analysis revealed that patients with LLA had signs of chronic vascular inflammation accompanied in the majority of cases by hyperhomocysteinemia with endothelial dysfunction, as well as direct association between the degree of the vascular inflammatory reaction and severity of clinical manifestations of lower limb ischaemia.

Peculiarities of atherosclerotic injury of carotid arteries were studied in 47 patients with coronary artery disease in dependence of blood concentration of homocysteine. The patients were divided in 2 groups -- with homocysteine concentration more and less than 10 mmol/l, and in 4 groups, corresponding to quartiles of distribution of homocysteine in blood. Ultrasound method was used for assessment of carotid artery intima-media thickness (IMT), detection of presence and character of atherosclerotic plaques and estimation of degree of carotid artery narrowing. It was established that elevation of blood homocysteine concentration was accompanied with increase of IMT, number of atherosclerotic plaques, and. Positive correlation was found between homocysteine level and IMT (r=0.38, p<0.05), degree of narrowing of carotid arteries (r=0.47, p<0.05), character of atherosclerotic plaques (r=0.43, p<0.05).

The prolonged observations of the immunological effectiveness of adsorbed diphtheria-tetanus toxoid with reduced antigen content in children who had received the primary course of immunization with this preparation showed that the preparation induced the development of prolonged and intensive immunity to both infections. In 2-3 years after the first booster immunization the protective level of diphtheria antitoxin was registered in 89.9% and that of tetanus antitoxin, in 99% of children. 6 years later the level of immunity remained practically unchanged: the titers of diphtheria antitoxin above the protection level were determined in 92% and those of tetanus antitoxin, in 97% of children. These data made it possible to increase intervals between booster immunizations to 6-7 years in children of this category. The results of the epidemiological trial made to find out the possibility of a change in the timing of the second booster immunization confirmed the expediency of postponing booster immunization from 6 and 11 years to 9 and 16 years of age.

Prolonged observations on the spread of toxigenic C. diphtheriae carriership, made during a school year in 12 groups of immune children (3809 children), showed that the penetration of diphtherial infection could give rise to the outbreak of bacterial carriership, its level being as high as 20.9-35.1% of the total number of children in the group. The spread of bacterial carriership occurred during the first months after the penetration of the infection, achieving its peak, then followed the subsidence of the infection in the focus. Though some children in the group persistently released C. diphtheriae, almost no new cases of carriership were registered in spring. The highest spread of carriership (55.6-73%) was revealed in the first forms of boarding schools despite a higher level of antitoxic immunity in these children. Cases of the spontaneous cessation of carriership were observed. The spread and subsidence of carriership were determined by the presence or absence of a susceptible contingent. Tests on guinea pigs, carried out in the course of this study to determine the toxigenicity of C. diphtheriae, showed its variability.

The authors examined 25 patients with acute abscesses and gangrene of the lungs to study the condition of the phagocyte system and its effect on processes of fibrin formation and destruction in the focus of inflammation. They found marked increase of the number of polymorphonuclear leucocytes and decrease of alveolar macrophages in lavage fluid of the diseased lung. The fibrinolytic, procoagulant, and oxygen-dependent metabolic activity of phagocytes was increased. With the degree of these changes and the clinical and endoscopic signs of the activity of the inflammatory process taken into account, the choice of the fibrinolysis activators and inhibitors for endobronchial administration can be differentiated and the results of treatment improved.

The studies demonstrated the immunological and epidemiological effectiveness of a single injection of adsorbed diphtheria-tetanus toxoid with reduced antigen content for adults: intense antidiphtheria immunity in 92.3% of the vaccinees 1-3 months and in 94.5% of the vaccinees 1 year after the injection. This immunity remained sufficiently intense for 3 years (the term of observation). The geometric mean of antitoxic titers was 0.84 I. U./ml. The highest intensity of immunity appearing after the injection was observed in persons aged 18-20 years who showed the highest antitoxic titers (exceeding 0.5 I. U./ml) in 100% of cases, the lowest intensity was registered in the age group of 30-39 years; in 14.2% of these vaccinees antitoxic titers were below the protective level. In other age groups (40-49 years, 50 years and over) the intensity of immunity was high. The geometric mean of the titers of diphtheria antitoxin were 1.2 I. U./ml and 2.1 I. U./ml respectively. In none of the foci under study the spread of the manifest forms of the disease was observed.