The aim of the work was to assess the T-cell and humoral immune arms in patients with acute coronary syndrome (ACS) recovered from or not exposed to COVID-19. 86 men with ACS aged 40 to 65 years old, who suffered or not exposed to COVID-19, which required stenting of coronary arteries, were examined. Depending on the peripheral blood B-lymphocyte CD3–CD19+CD5+ level and the former COVID-19 history, all patients were divided into 6 groups. Of the previously COVID-19 exposed subjects CD3–CD19+CD5+ lymphocytes were at: reduced (group 1), normal (group 2), increased (group 3) level. COVID-19 unexposed subjects had CD3–CD19+CD5+ lymphocyte level: reduced (group 4), normal (group 5), increased (group 6). The most severe clinical manifestations were observed in group 1: with a larger rate of stent thrombosis and increased mortality. In absolute numbers, T-lymphocytes were significantly lower in group 1 compared to other groups, except group 4. The lowest both relative and absolute T-helper cell counts were recorded in covid-19 patients, with reduced CD3–CD19+CD5+ cell level. NK-lymphocytes both in relative and absolute level were significantly (p 0.05) higher in patients who suffered from COVID-19 as compared to those in patients unexposed to previous COVID-19. Percentage of late-activation T-regulatory cells was minimal in patients with former COVID-19 along with high B-lymphocyte CD3–CD19+CD5+ level, which significantly (p 0.05) differed from those in subjects lacking former COVID-19 history. In addition, significantly lower B-lymphocyte CD3–CD19+CD5– level was found in group 1 and 4. The IgM level peaked in group 5 — subjects lacking former COVID-19 history and having normal CD3–CD19+CD5+ cell level that significantly differed in comparison with that of in group 1, 2, 3. At the same time, the maximum value of IgG level was recorded in COVID-19 patients with normal CD3–CD19+CD5+ cells, and significantly differed from those found in group 5 and 6. C1-inhibitor level was higher in group 3 that significantly differed from that in other groups. SARS-CoV-2-specific IgG and IgM levels were significantly higher in COVID-19-positive vs. COVID-19-negative patients. Conclusion. In patients who have suffered COVID-19 with low B-lymphocyte CD3–CD19+CD5+ level, a significantly compromised immune protection was noted in comparison with other groups: a decline in total T-lymphocyte, T-helper, early- and late-activation T-lymphocyte, T-regulatory cell, B-lymphocyte CD3–CD19+CD5– levels, which was associated with a more severe disease course characterized by stent thrombosis and large mortality.

Acute COVID-19 is a viral infection caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in dramatically decreased peripheral blood CD3+T cell count apparently due to alterations of thymic T cell maturation, that can persist long term afterwards. Therefore, we analyzed the levels of peripheral blood TRECs (T-cell receptor excision circles), and investigated the main alterations in peripheral blood T cell subsets in COVID-19 convalescents. We performed molecular quantification of TRECs with “TREC/KREC-AMP PS” kit and flow cytometric analysis of peripheral blood lymphocytes from three groups of patients. The first group contained 109 samples from COVID-19 convalescents (6–12 month post-acute COVID-19) with normal levels of TRECs (TRECn); the second was formed from COVID-19 convalescents (6–12 month post-acute COVID-19) with decreased levels of TRECs (TREClow, n = 29), and healthy control group (HC, n = 18). We noticed no significant differences between all three groups in CD3+T cell relative and absolute numbers. However, CD4+T cell frequencies were decreased in TREClow and TRECn groups compared to HC (40.8% (31.6; 50.1) and 46.4% (40.0; 53.0) vs 53.5% (47.36; 56.9), p 0.001 and р = 0.004, respectively). Furthermore, Th cell levels were decreased in TREClow patients vs HC and TRECn groups (701 cell/1 µL (478; 807) vs 1005 cell/1 µL (700; 1419), р = 0.020, and 876 cell/ 1 µL (661; 1046), р = 0.008, respectively). Finally, both groups of COVID-19 convalescents had increased frequencies of circulating CD8+T cells — 29.4% (20.7; 39.7) in TREClow group, 26.5% (21.1; 32.7) in TRECn group vs 21.3% (17.1; 26.0) in healthy controls (p = 0.024 and р = 0.026, respectively). In TRECn group, CD8+T cell count was elevated vs control range (508 cell/1 µL (372; 622) vs 356 cell/1 µL (247; 531), р = 0.044). Thus, COVID-19 convalescents (6–12 month post-acute COVID-19) showed an imbalance in CD4+and CD8+T cell level even at 6–12 months post-acute SARS-CoV-2 infection, and the observed changes in peripheral blood T cells could be closely related to the alterations in thymic T cell maturation and differentiation. Such a long-term decline in TREC levels in the circulation may have a profound impact on immune system functions and requires immunocorrection therapy.

3 ФБУН ФНИИВИ «ВИРОМ» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека, Екатеринбург; 4 Медико-биологический университет инноваций и непрерывного образования ФГБУ «Государственный научный центр Российской Федерации -Федеральный медицинский биофизический

Objective: to evaluate the dynamics of the T- and B-cell immunity in patients with acute coronary syndrome (ACS) who have and have not had COVID-19, depending on the number of CD3+CD8+T-lymphocytes.Materials and methods: 65 men with ACS who underwent coronary artery stenting were examined. Immunological parameters were studied using flow cytometry, a complete blood count at baseline and 28 days after admission.Results: The maximum troponin level was observed in individuals with ACS who had recovered from COVID-19 and had a normal level of CD3+CD8+T cells. Stent thromboses and deaths occurred only among patients with a history of COVID-19, mainly with reduced CD3+CD8+T- cells, for which indicators of immune status were determined over time. The absolute numbers of T lymphocytes, T helper cells, late activated T lymphocytes, B lymphocytes (CD3-CD19+CD5+), B lymphocytes (CD45+CD3-CD19+) were minimal in individuals with low CD3+CD8+ T lymphocytes who had previously suffered from COVID-19, and significantly increased in their dynamics after 28 days. Natural killer cells significantly increased in dynamics in patients with initially low and normal CD3+CD8+T-lymphocytes who suffered from COVID-19.Conclusions: after stenting of the coronary arteries over time, in people with reduced CD3+CD8+Tlymphocytes and patients with COVID-19, T-lymphocytes (CD45+CD3+CD19-), T-helper cells, CD3+CD8+T-lymphocytes significantly increased, T-NK lymphocytes, NK lymphocytes, late-activated T-lymphocytes, T-regulatory lymphocytes and late-activated T-regulatory cells, B-lymphocytes, immunoglobulin G and complement fragment C3a decreased. T-regulatory lymphocytes and late-activated T-regulatory cells were significantly reduced in patients without prior COVID-19 with baseline low CD3+CD8+T-lymphocytes. In individuals with normal CD3+CD8+T-lymphocytes who recovered from COVID-19, T-lymphocytes (CD45+CD3+CD19-), NK-lymphocytes, and late-activated T-lymphocytes increased over time.

The 2019 coronavirus disease (COVID-19) pandemic has had an unprecedented impact on health and economies around the world. Direct myocardial injury and cytokine storm, leading to destabilization of preexisting plaques and accelerated formation of new plaques, are two mechanisms that trigger the acute coronary syndrome in COVID-19. There is insufficient data on the immune status of patients with acute coronary syndrome who have undergone COVID-19. The aim of the study was to study T and B cell, humoral immunity depending on the number of cytotoxic T lymphocytes (CD8+) in patients with acute coronary syndrome who underwent COVID-19. Materials and methods of research: 65 men with unstable angina pectoris and acute myocardial infarction (acute coronary syndrome) from 40 to 65 years old, who had previously had COVID-19, were examined. A study of peripheral blood was carried out: complete blood count (Medonic device, Sweden), general and specific IgM, IgG, IgA, compliment fragments (Vector Best, Russia). Subpopulations of T and B lymphocytes were determined by flow cytometry. In persons with acute coronary syndrome who underwent COVID-19 with predominantly normal and elevated levels of cytotoxic T cells, a more severe course of the disease was observed: patients with acute myocardial infarction prevailed, they had longer mortality, longer treatment duration, and stent thrombosis was more common. In patients with elevated cytotoxic T cells, there was a maximum increase in erythrocytes, hemoglobin, hematocrit, lymphocytes of both the total number and subpopulations – T helpers, T-NK lymphocytes, NK lymphocytes, T lymphocytes of early and late activation, B1 and B2 lymphocytes, index of NBT-induced test. In patients with normal levels of NK cells, compared with other groups, there was an increase in spontaneous NBT activity and index, a significant decrease in C3a and C5a complement fragments. Prevalence of stent thrombosis and mortality in the group of patients with normal levels of cytotoxic T cells may indicate torpidity of the immune system in these patients with poor outcomes.

УДК 616.12-07 ПОКАЗАТЕЛИ СТРУКТУРЫ И ФУНКЦИИ ЛЕВОГО ЖЕЛУДОЧКА И УРОВЕНЬ АРТЕРИАЛЬНОГО ДАВЛЕНИЯ ПОСЛЕ ПЕРЕНЕСЕННОЙ ИНФЕКЦИИ COVID-19 С ПОРАЖЕНИЕМ ЛЕГКИХ (ПРОСПЕКТИВНОЕ 6-МЕСЯЧНОЕ НАБЛЮДЕНИЕ)Григоричева Е.А. 1

We examined 23 patients aged 40 to 65 years (mean age 54.526.72) with a diagnosis of acute coronary syndrome (ACS) at admission, who underwent emergency or delayed coronary stenting a day later. All patients had arterial hypertension as a concomitant disease. Upon additional examination, blood troponin levels were determined, ECG was performed in the time dynamics. Acute myocardial infarction with ST elevation was diagnosed in 7 patients, infarction without ST elevation, in 6 patients, the unstable angina rest, in the rest of this group (Grace risk from 75 to 150 points, on average, 107.727.16 points). To assess the immune status, especially, lymphocyte populations and subsets we used standardized techniques, i.e., flow cytometric assays with Navios cytofluorimeter (Beckman Coulter, USA). The following subpopulations were determined: CD45+ (panleukocyte marker for gating lymphocytes), CD45+, CD3+ (T cells), CD45+, CD3+, CD4+ (helper inducers), CD45+, CD3+, CD8+ (cytotoxic T cells), CD45+, CD3+CD16+, CD56+ (TNK cells) CD45+, CD3-, CD16+, CD56+ (natural killer cells), CD45+, CD3-, CD19+CD5+ (B cells), CD45+, CD3+, CD4+, CD25+ (activated helpers, early activation phase), CD45+, CD3+, HLA-DR (activated T lymphocytes late activation phase). The data obtained indicate that the relative indices of T helper subpopulations, T cells at early and late activation step, and B lymphocytes were increased in the patients with acute coronary syndrome, compared with control group. At the same time, there is a trend for increasing absolute values of these indexes. The subpopulation of TNK lymphocytes proved to be significantly increased both in relative and absolute values, whereas percentages of CD45+CD3+CD19- (p 0.01) and T cytotoxic lymphocytes (p 0.001) were decreased and showed the same trend in absolute terms. The ratio of CD4/CD8 lymphocytes was almost doubled (p 0.001), due to increased content of T-helpers and decrease in cytotoxic T lymphocytes. In clinical blood analyses of ACS patients a tendency for leukocytosis was shown, (10.155.22), with a shift to the band forms.

ВОЗДЕЙСТВИЕ ИЗОСОРБИДА МОНОНИТРАТА НА СЕРДЕЧНЫЙ РИТМ У ПАЦИЕНТОВ СО СТАБИЛЬНОЙ СТЕНОКАРДИЕЙ НАПРЯЖЕНИЯ 1-ГО И 2-ГО ФУНКЦИОНАЛЬНЫХ КЛАССОВСафронова Э.А. 1 , Григоричева Е

ВОЗДЕЙСТВИЕ НА РИТМ СЕРДЦА И ЕГО ВАРИАБЕЛЬНОСТЬ ИЗОСОРБИДА МОНОНИТРАТА У ПАЦИЕНТОВ СО СТАБИЛЬНОЙ СТЕНОКАРДИЕЙ НАПРЯЖЕНИЯ 1 И 2 ФУНКЦИОНАЛЬНЫХ КЛАССОВ В СОЧЕТАНИИ С ГИПЕРТОНИЧЕСКОЙ БОЛЕЗНЬЮСафронова Э.А. 1 , Харламова У.В. 1 , Кузин А.И. 1 , Шамаева Т

Aim. To study the effect of nitroglycerin on the heart rate and its variability in patients with stable angina pectoris class 1 and 2. Methods. 85 men with stable angina pectoris class 1 and 2 pathologies were examined between 2007 and 2012 in the City Clinical Hospital No. 8 of Chelyabinsk (mean age 53.15.66 years). In addition to common methods, a rhythmocardiographic study was performed, which allows you to calculate heart rate variability. An electrocardiogram was recorded simultaneously with the rhythmocardiogram. Results. After sublingual nitroglycerin, the number of ventricular extrasystoles decreased in the background test and during Valsalva maneuver, increased in the Ashner's test and an exercise stress tests and did not change in the orthostatic test. An increase in supraventricular extrasystoles after nitroglycerin administration occurred in 10.6% of patients. Nitroglycerin administration resulted in a decrease in the inter-systolic intervals, an increased in the proportion of slow low-frequency waves statistically significant in the background and an exercise stress test. Spectral indicators of cardiac sympathetic modulation significantly increased in the Ashners test and decreased in the background test, while spectral indicators of cardiac parasympathetic modulation decreased in all samples except in exercise stress tests. Conclusion. Under the influence of nitroglycerin, supraventricular arrhythmias increased in all vegetative tests except for orthostatic, the number/severity of ventricular extrasystoles ambiguously changed: decreased in Valsalva manoeuvre the background test, did not change in orthostatic and increased in Aschner's and an exercise stress tests; after nitroglycerin, the proportions of sympathetic influence (in Ashner's test) and slow low-frequency waves in the spectrum of the vegetative modulation increased with a decrease in parasympathetic.

АРИТМОГЕННОЕ ДЕЙСТВИЕ НИТРОГЛИЦЕРИНА У ПАЦИЕНТОВ СО СТАБИЛЬНОЙ СТЕНОКАРДИЕЙ НАПРЯЖЕНИЯ 1 И 2 ФУНКЦИОНАЛЬНЫХ КЛАССОВСафронова Э.А. 1 , Кузин А

ВОЗДЕЙСТВИЕ ИЗОСОРБИДА ДИНИТРАТА НА НАРУШЕНИЯ РИТМА СЕРДЦА У БОЛЬНЫХ СО СТАБИЛЬНОЙ СТЕНОКАРДИЕЙ НАПРЯЖЕНИЯСафронова Э

ФГБОУ ВО «Южно-Уральский государственный медицинский университет» Министерства здравоохранения Российской Федерации, Челябинск, e-mail: safronovaeleonora68@gmail.com В статье представлены результаты изучения динамики показателей оксидативного стресса на прием нитроглицерина у больных со стабильной стенокардией напряжения 3 и 4 функциональных классов и нестабильной стенокардией. Были изучены следующие показатели хемилюминесценции в сыворотке и цельной крови: светосумма, спонтанная и максимальная светимость, вспышка, тангенс угла наклона кривой хемилюминесценции. При стабильной стенокардией напряжения 3 и 4 функциональных классов и нестабильной стенокардии отмечено увеличение содержание активных форм кислорода в сыворотке крови и цельной крови по сравнению с контрольной группой. У пациентов с нестабильной стенокардией отмечались большая способность липидов крови к перекисному окислению при сравнении с пациентами со стабильной стенокардией напряжения 3 и 4 ФК. Гетерогенность реакции на нитроглицерин связана с исходным состоянием окислительного стресса: чем ниже уровень исходного содержания активных форм кислорода, тем выше реакция окислительного стресса в сторону увеличения в ответ на нитроглицерин. При стабильной стенокардии напряжения произошло увеличение интенсивности генерации активных кислородных метаболитов, способности липидов крови к перекисному окислению, содержания гидроперекисей. При исходно повышенных показателях окислительного стресса под влиянием нитроглицерина произошло снижение перекисного окисления липидов, интенсивности генерации активных кислородных метаболитов, гидроксил-радикалов. При нестабильной стенокардии при исходно нормальных показателях активных форм кислорода или статистически от них не отличающихся, динамика окислительного стресса под воздействием нитроглицерина связана преимущественно с повышением интенсивности генерации активных кислородных метаболитов, гидроперекисей липидов, потенциальной способности липидов к перекисному окислению, что оказывает повреждающее действие на эндотелий. При исходно повышенных уровнях активных форм кислорода у лиц с нестабильной стенокардией наблюдалось снижение интенсивности образования гидроксил-радикалов, генерации активных кислородных метаболитов. Полученные данные могут быть использованы для прогнозирования безопасного приема нитроглицерина у больных со стабильной и нестабильной стенокардией. Ключевые слова: оксидативный стресс, активные формы кислорода, стабильная стенокардия напряжения, нестабильная стенокардия, нитроглицерин, хемилюминесценция.

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Aim. To evaluate the peripheral autonomic effects of isosorbide mononitrate on sinoatrial node pacemaker activity using wave structure analysis by rhythmocardiography. Methods. The study included 162 patients with III and IV functional classes of stable angina, among them 122 - with hypertension. The control group consisted of 42 healthy volunteers. In addition to standard techniques (electrocardiography, echocardiography, bicycle ergometry, electrocardiogram daily monitoring), high-resolution rhythmocardiography using a KAP-RK-01-«Mikor» diagnostic complex with time and spectral analysis of the sinus rhythm wave structure was performed. The method is based on the evaluation of peripheral autonomic regulation in the sinoatrial pacemaker and influence of humoral and metabolic environment on it. Results. In all patients with III and IV functional classes of stable angina regardless of the concomitant arterial hypertension heart rate variability, as well as Valsalva maneuver response increased in a number of patients taking isosorbide mononitrate. Negative events related to isosorbide mononitrate intake were reduced parasympathetic fluctuations in a number of cases, humoral-metabolic regulation growth, and increase of sympathetic regulation role in patients with concomitant arterial hypertension. Rhythmocardiography allowed to access the influence of isosorbide mononitrate on heart rate variability in patients with ischemic heart disease. Conclusion. Both positive (increased heart rate variability) and negative (spectral features redistribution with humoral, metabolic and sympathetic components increase and parasympathetic component decrease) effects were associated with isosorbide mononitrate intake with lesser sinoatrial node dysregulation in patients with concomitant arterial hypertension.

The pharmacological test with the use of high-resolution rhythmocardiography for the analysis of cardiac rhythm variability associated with peripheral vegetative regulation of the synoatrial node was applied to study effects of a single dose of organic nitrates (nitroglycerin and mononitrate isosorbide) in 41 patients with unstable angina. Rhythmocardiograms were obtained before and after a morning sublingual dose of nitrates preceding intake of basal drugs. The results suggest negative action of nitrates on peripheral vegetative regulation of pacemaker activity of the synoatrial node.

The paper presents the study of arrhythmogenic action of nitroglycerin (NG), including atrial conduction. All patients were surveyedritmokardiografic study with simultaneous recording of the electrocardiogram before and after a single dose NG. In a number of cases have been detected arrhythmias, among whom were paroxysmal atrial fibrillation, pacemaker migration to the atria.