[Risk factors for the early development of septic shock in patients with severe COVID-19].

AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.

[Treatment of chronic viral hepatitis C with direct acting antiviral agent: review].

HCV infection treatment regimens are viewed from positions of HCV life cycle and replication, effects of NS3/4A protease inhibitors and NS5A/NS5B inhibitors on HCV strain replication. Evolution of HCV treatment regimens from its discovery to modern DAA agents had led to substantial progress although drug resistance poses a new issue to be addressed.

[T-cells immunity in oral lichen planus pathogenesis].

In this review the modern ideas of the cell-like immune pathogenesis mechanism of Lichen planus)LP) are described. The special attention is paid to molecular diagnostics methods ( immunohistochemical and others). Communication of emergence of oral LP with infectious diseases is shown.

[Specific features of lymphoid infiltration in liver biopsy in patients with chronic viral hepatitis B and C].

AIM: To study characteristics of leukocytic infiltration of the liver in patients with chronic viral hepatitis B and C (CVHB and CVHC) with consideration of hepatitis activity and fibrosis severity. MATERIAL AND METHODS: The examination of 37 patients with CVHB (n = 13) and CVHC (n = 24) included liver puncture biopsy by Mengini, subsequent histological and morphological investigation of liver biopsy with immunohisto- and immunocytochemistry. RESULTS: In CVHB and CVHC patients leukocytic infiltrates (LI) of the liver present primarily with T-lymphocytes (CD3+), NKT cells (CD3+CD16+CD56+), NK cells (CD16+CD56+), T-regulatory lymphocytes (CD4+CD25+), cytotoxic T-lymphocytes (CD8+). Cytotoxic lymphocytes (CD8+) and NK cells (CD16+CD56+) detected in hepatic LI of patients with chronic viral hepatitis are similar in composition with cells in hepatic tissue infiltrates in autoimmune hepatitis. We are the first to detect the complex of T-regulatory cells (CD4+CD25+) in hepatic parenchyma of these patients. This complex suppresses cellular immune response in virus elimination and damaged tissues and supports development of persistent viral infection with autoimmune component. CONCLUSION: The complex of T-regulatory cells (CD4+CD25+) isolated in hepatic LI evidences for existence of a morphofunctional base for autoimmune manifestations in the presence of persistent viral infection.

[Lymphocyte subpopulation composition in hepatic tissue and autoimmune manifestations in viral hepatitis].

This work had the aim to study the role of disbalance of inflammatory procytokines, lymphocyte subpopulation composition in peripheral blood, and cell populations of hepatic tissue in pathogenesis of viral hepatitis. A total of 159 patients with chronic hepatitis B and C were examined. They proved to exhibit signs of autoimmune processes (ASMA, ANA, AMA, anti-LKM-1, RF, CG) and cytokine (IL-1b, TNFa) disbalance. The number of lymphocytes expressing HLADR+ was shown to increase and CD+ lymphocyte to decrease in proportion to the severity of periportal necrosis, portal inflammation, intralobular degeneration and fibrosis compared with healthy donors. Hepatic biopsies contained T-regulatory cell complex (CD4+ CD25+). These data give evidence of the morphofunctional basis for autoimmune manifestations in patients with persistent viral hepatitis infection.

[Characteristics of the cytokine profile and peripheral blood lymphocyte subpopulations in patients with chronic viral hepatitis B and C in comparison to severity of morphological changes of the liver].

AIM: To study cytokine concentration in blood serum in spontaneous and NDV- and PGA stimulated production by peripheral blood mononuclear cells (PBMC) and contents of peripheral blood lymphocyte subpopulations when compared with severity of morphological changes of the liver in patients with chronic viral hepatitis B and C (CHB and CHC). MATERIAL AND METHODS: A total of 37 patients entered the trial (13 with CHB and 24 with CHC). Concentrations of IFN-alpha, IFN-gamma, TNF-alpha, IL-1beta, IL-4, IL-6 in blood serum in spontaneous and NDV and PGA stimulated PBMC production, content of CD3, CD4, CD8, CD16, CD25, HLADR, CD20, CD38 subpopulations of peripheral blood lymphocytes were examined. Also, puncture biopsy of the liver by Mengini was made with subsequent estimation of the histological activity index by R. Knodell adapted to hepatitis B and C by K. Ishak. RESULTS: Patients with CHB and CHC in minimal activity of the process and insignificant morphological changes in the liver demonstrated a significant fall of NDV induced IFN-alpha production. Patients with highly active hepatitis and maximal morphological changes in the liver had significant lowering of NDV induced production of IFN-alpha, IFN-gamma, TNF-alpha, IL-6 and PGA induced production of TNF-alpha. CONCLUSION: CHB and CHC patients should be examined not only with estimation of serum cytokines concentration but also NDVand PGA stimulated production of PBMC should be taken into consideration with calculation of immunoregulatory index for prognosis of the disease and choice of adequate therapy.

[Time course changes in cytokines content and gas composition in blood of patients with salmonellosis and acute shigellosis].

AIM: To study changes in serum concentrations of interleukines (IL) and tumor necrosis factor alpha (TNFa) in the course of acute moderate and severe shigellosis and salmonellosis; to elicit their correlation with disorders of gas and electrolyte blood composition and acid-base balance (ABB). MATERIAL AND METHODS: A total of 39 patients with salmonellosis and 32 patients with acute shigellosis admitted to infectious hospital N 2 entered the study. The following parameters were assessed: serum concentrations of IL-1, IL-IO and TNFa; ABB, gas and electrolyte blood composition; leucocytic intoxication index (LII). The tests were made on the disease day 2-3 and 6-7 (in severe salmonellosis on day 10-11). RESULTS: In moderate salmonellesis and acute shigellosis the level of proinflammatory cytokines (IL-1 and TNFa) diminished while in severe acute intestinal infection their concentration was high reflecting imbalance of immune response. Content of IL-10 depends on etiology and severity of the course of infectious process - the highest IL-10 concentrations were found in patients with severe salmonellosis on the disease day 10-11. A direct correlation was confirmed between IL-1, TNFa and LII in the disease onset in all patients with acute intestinal infections. CONCLUSION: An important role of IL-1, IL-10 and TNFa in pathogenesis of bacterial intestinal infections is confirmed. A correlation exists between blood gas composition and concentration of cytokines.

[Humoral and cellular adaptation mechanisms in development of intoxication syndrome in patients with acute viral hepatitis]. / Gumoral'nye i kletochnye adaptatsionnye mekhanizmy pri razvitii intoksikatsionnogo sindroma u bol'nykh ostrymi virusnymi gepatitami.

AIM: To study endotoxin-binding function of blood in patients with acute viral hepatitis (AVH) in the course of the disease. MATERIAL AND METHODS: A total of 335 patients with AVH were examined. The titers of IgG antiendotoxin antibodies to glycolipid of Re-chemotype were estimated in enzyme immunoassay (Diaendotox-2 kit), endotoxin-binding activity (EBA) of high density lipoproteins (HDLP) in EIA with the kit Liprobind (Microecos). The number of polymorphonuclear leukocytes (PL) binding lipopolysaccharides were counted by M. Yu. Yakovlev et al. method. For detection of PL binding endotoxin of gram-negative bacteria, kits Endim (Microecos) were used, beta2-microglobulin was estimated by a radioimmunoassay using kits made in Belarus Institute of Bioorganic Chemistry. Registration of chemoluminescence was conducted on chemiluminometer LBK 1251 (Finland) by M. Wilson (1985) method. RESULTS: In moderate AVH at the height of intoxication a low Re-antibodies level was recorded irrespective of the disease etiology. To convalescence this level went up. PL reserves in AVH patients were low except patients with AVH C who had unaffected neutrophil reverves in relation to LPS binding. At the height of AVH, HDLP EBA was very high in all the groups with normalization to convalescence. In VHC high HDLP EBA persisted as long as the disease course. A significant rise of beta2-microglobulin was seen in all the groups of AVH patients, its severity correlating with the degree of the disease severity. CONCLUSION: One of the leading factors in development of indoxication in AVH patients is a lipopolysaccharide complex of gram-negative intestinal bacteria actively coming into blood flow due to hepatocyte cytolysis. In response to LPS action there appeared a stereotypic adaptation complex of reactions in the form of activation of cellular and humoral immune response.

[Autoimmune manifestations in acute viral hepatitides]. / Autoimmunnye proiavleniia pri ostrykh virusnykh gepatitakh.

AIM: To study autoimmune reactions in patients with acute viral hepatitis A, B, and C in the dynamics of an infectious process. MATERIALS AND METHODS: 134 patients with acute viral hepatitides of various etiology were examined. Among them there were 36 patients with acute viral hepatitis A, 40 with B, and 58 with viral hepatitis C. Antinuclear antibodies (ANA), antismooth muscle antibodies (SMA), and antimitochondrial antibodies (AMA) were determined by immunofluoresence assay using the test systems ATS COMVI-1, IMMCO diagnostics (USA). Serum rheumatoid factor was detected by the semiquantitative latex-agglutination test on a slide manufactured by the "Human" firm (Germany). Cryoglobulins were identified by the qualitative visual method. RESULTS: SMA, ANA were detected in the diagnostically significant titers (1:40-1:160) in patients with acute viral hepatitis A, B, and C. A distinction of autoimmune manifestations was ascertained in viral hepatitis C. It has been demonstrated that in 71% of the patients cryoglobulins appear in the acute period of the disease and, in their presence, rheumatoid factor was found in 17.2% and 6.9% exhibited anti-LKM-1 and AMA. CONCLUSION: The presented data on the nature and time course of changes in autoimmune reactions in patients with acute viral hepatitis A, B, and C during an infectious process suggest that autoimmune disorders are characteristic of viral hepatic lesions just at the early stages of the disease irrespective of its etiology and play a prominent role in the pathogenesis of these nosological entities.

[Changes in the levels of acute phase proteins in viral hepatitis]. / Dinamika urovnia belkov ostroi fazy pri virusnykh porazheniiakh pecheni.

AIM: To investigate changes in the levels of acute phase proteins (APP) in the serum of patients with acute and chronic viral hepatitis of various etiology. MATERIAL AND METHODS: APP (prealbumin, albumin, transferrin, haptoglobin) were measured by automatic kinetic analyzer JCS II TM (Beckman) in 92 patients with acute and 61 patients with chronic viral hepatitis. Synthesis of albumin, prealbumin was depressed, of haptoglobin increased in patients with acute viral hepatitis irrespective of etiology at the height of intoxication. In chronic viral diseases APP content depended on the disease etiology. In chronic hepatitis C, B + C and D albumin, haptoglobin and transferrin were low in clinical exacerbation while in patients with chronic hepatitis B a fall in albumin, prealbumin and transferrin is accompanied with high haptoglobin. CONCLUSION: A complicated multidirectional changes in APP in patients with acute or chronic hepatitis serve, on the one hand, an integral diagnostic indication of hepatic function in conditions of systemic endotoxemia. On the other hand, endotoxemia is caused by lipopolysaccharides of gram-negative bacteria entering blood flow in great amounts in morphofunctional hepatic disorders caused by viral hepatitis of different etiology.

[Clinico-pathogenetic features of viral hepatitis A course]. / Kliniko-patogeneticheskie osobennosti techeniia virusnogo gepatita A.

AIM: To study mechanisms enhancing realization of autoimmune disorders in acute viral hepatitis A at initial stages. MATERIALS AND METHODS: 32 patients with moderate and 4 patients with severe VHA (17 females and 19 males, age from 15 to 38 years) verified by finding serum anti-HAV IgM at enzyme immunoassay (EIA) have undergone examination which included: measurement of beta 2-microglobulin, C5-components of complement, circulating immune complexes (CIC), zero lymphocytes; test for antinuclear antibodies (ANA) and smooth muscle antibodies (SMA). RESULTS: All the patients exhibited high levels of beta 2-microglobulin, zero lymphocytes, CIC, low concentration of C5-components of complement. SMA were detected at the height of intoxication in 27 patients, in early convalescence--in 31 patients. ANA were discovered only in one patient. CONCLUSION: The findings suggest development of autoimmune reactions in acute VHA patients. These reactions may trigger onset of autoimmune hepatitis.