A new virus from the group of coronaviruses was identified as the cause of atypical pneumonia and called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and disease called Corona Virus ...Disease (COVID-19). During the cytokine storm, the main cause of the death, proinflammatory cytokines are released which stimulate further tissue destruction. Galectin-1 (Gal-1) is a pleiotropic cytokine involved in many immune and inflammatory processes and its role in COVID-19 is still unknown. The aim of this study was to determine systemic values of Gal-1 and correlations between Gal-1 and proinflammatory cytokines and clinical parameters during COVID-19 progression. This is observational and cross-sectional study. 210 COVID-19 patients were included and divided into mild, severe or critical group according to COVID-19 severity. Serum levels of IL-1β, IL-6, IL-10, IL-23, IL-33 and Gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Systemic levels of IL-1β, IL-6, IL-10, IL-23, IL-33 and Gal-1 were significantly higher in stage III of COVID-19 patients compared to stage I and II. There were no significant differences in the ratio between Gal-1 and IL-10 with proinflammatory cytokines. Positive correlation was detected between Gal-1 and IL-1β, IL6, IL-10, IL-23 and IL-33. Gal-1 positively correlated with chest radiographic finding, dry cough and headache and negatively correlated with normal breathing sound. Linear regression model and ROC curve analysis point on Gal-1 as significant predictor for COVID-19 severity. Presented results implicate on Gal-1 and IL-10 dependent immunomodulation. The precise mechanism of Gal-1 effect in COVID-19 and its potential as a stage marker of disease severity is still to be clarified.
Galectin-3 (Gal-3), multifunctional protein plays important roles in inflammatory response, infection and fibrosis. The goal of study was to determine the association of Gal-3, immune response, ...clinical, biochemical, and radiographic findings with COVID-19 severity. Study included 280 COVID-19 patients classified according to disease severity into mild, moderate, severe and critical group. Cytokines, clinical, biochemical, radiographic data and peripheral blood immune cell make up were analyzed. Patients in critical group had significantly higher serum level of Gal-3, IL-1β, TNF-α, IL-12, IL-10 compared to the patients in less severe stages of disease. Strong positive correlation was detected between Gal-3 and IL-1β, moderate positive correlation between Gal-3, TNF-α and IL-12, moderate negative correlation between Gal-3, IL-10/IL-1β and IL-10/TNF-α. Moderate positive correlation noted between Gal-3 and urea, D dimer, CXR findings. Strong negative correlation detected between Gal-3 and p0
, Sa0
and moderate negative correlation between Gal-3, lymphocyte and monocyte percentage. In the peripheral blood of patients with more severe stages of COVID-19 we detected significantly increased percentages of CD56
CD3
TNF-α
T cells and CD56
CD3
Gal-3
T cells and increased expression of CCR5 in PBMCs. Our results predict Gal-3 as an important marker for critical stage of COVID-19. Higher expression of Gal-3, TNF-α and CCR5 on T cells implicate on promoting inflammation and more severe form of disease.
Clinical manifestations of SARS-CoV-2 infection range from mild to critically severe. The aim of the study was to highlight the immunological events associated with the severity of SARS-CoV-2 ...infection, with an emphasis on cells of innate immunity. Thirty COVID-19 patients with mild/moderate symptoms and 27 patients with severe/critically severe symptoms were recruited from the Clinical Center of Kragujevac during April 2020. Flow cytometric analysis was performed to reveal phenotypic and functional alterations of peripheral blood cells and to correlate them with the severity of the disease. In severe cases, the number of T and B lymphocytes, dendritic cells, NK cells, and HLA-DR-expressing cells was drastically decreased. In the monocyte population proportion between certain subsets was disturbed and cells coexpressing markers of M1 and M2 monocytes were found in intermediate and non-classical subsets. In mild cases decline in lymphocyte number was less pronounced and innate immunity was preserved as indicated by an increased number of myeloid and activated dendritic cells, NK cells that expressed activation marker at the same level as in control and by low expression of M2 marker in monocyte population. In patients with severe disease, both innate and adoptive immunity are devastated, while in patients with mild symptoms decline in lymphocyte number is lesser, and the innate immunity is preserved.
In chronically infected HCV patients emergence and evolution of fibrosis, as a consequence of virus persistence, can be considered as an indicator of disease advancement. Therefore the aim of this ...study was to correlate alterations of immune response in chronic HCV patients with liver histopathology. Sera cytokine levels and frequency of circulating and liver infiltrating cells were evaluated using 13plex Kit Flow Cytomix, flow cytometry and immunohistochemistry. We found that the number of circulating T lymphocytes (including CD4+, CD8+ and Treg) and B lymphocytes, as well as DCs, was higher in patients with no fibrosis than in healthy subjects. In patients with fibrosis frequency of these cells decreased, and contrarily, in the liver, number of T and B lymphocytes gradually increased with fibrosis. Importantly, in patients with advanced fibrosis, liver infiltrating regulatory T cells and DC-SIGN+ mononuclear cells with immunosuppressive and wound-healing effector functions were abundantly present. Cytokine profiling showed predominance of proinflammatory cytokines in patients with no fibrosis and a tendency of decline in level of all cytokines with severity of liver injury. Lower but sustained IL-4 production refers to Th2 predominance in higher stages of fibrosis. Altogether, our results reveal graduall alterations of immunological parameters during fibrosis evolution and illustrate the course of immunological events through disease progression.
The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our ...goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity.
In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed.
Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (
< 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory (neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin), arterial blood gases (oxygen saturation-Sa0
, partial pressure of oxygen -p0
), and chest X-rays (CXR) lung findings (
=
.000). We found a significantly higher serum concentration (
< 0.05) of TNF-α, IL-1β, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1β, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1β, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (
< 0.05) between pO
and serum IL-1β, IL-12, and IL-33 and between SaO
and serum IL-33 was noted. The positive relation (
< 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven.
In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1β, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.
Background and purpose: Host defense peptides have considerable therapeutic potential. One of the limitations for their therapeutic use is insufficient selectivity of some peptides, i.e. toxicity for ...eukaryotic cells. In this study, we have investigated effect of two naturally occurring and three analogs of frog skin-derived peptides on viability/proliferation of resting peripheral blood mononuclear cells and activated lymphocytes.Materials and Methods: Effect of tested peptides was assessed using MTT colorimetric assay. Concanavalin A was used as lymphocyte mitogen.Results: Brevinin-2GU induced cell death only in the highest tested concentration, whereas other peptides were not cytotoxic to resting peripheral blood mononuclear cells. Moreover, high concentrations of B2RP, D-Lys-Ascaphin-8 and Lys-XT-7 induced cell proliferation and this effect was more prominent in lymphocytes (p<0,05). Tested peptides had opposite effect on activated lymphocytes inhibiting proliferative response to Concanavalin A (Brevinin-2GU, B2RP and D-Lys-Temporin p<0,05). Conclusions: Tested peptides (with exception of Brevinin-2GU) didn’t show cytotoxicity toward peripheral blood mononuclear cells. Moreover, they have potential to modulate immune response by inducing proliferation of resting peripheral blood mononuclear cells and limiting proliferative response to the activation stimulus. Regarding their potent antimicrobial and low hemolytic activity this makes them good candidates for therapeutic use.Key words: host defence peptides; cytotoxicity; immunomodulation
Pseudomonas aeruginosa is a common cause of serious infections in hospitalized patients and is associated with high rates of hospital morbidity and mortality.
The aim of this study was to identify ...the risk factors of nosocomial infections caused by piperacillin-tazobactam-resistant P.aeruginosa (PT-RPA).
A case-control study was conducted in the Clinical Centre Kragujevac from January 2010 to December 2011.
In the observed period, 79 (38.16%) patients had PT-RPA infections, while 128 (61.84%) patients had infections caused by piperacillin-tazobactam-sensitive P. aeruginosa (PT-SPA). Pneumonia was more frequently found in the PT-RPA group (55.70%) (p < 0.05), whereas urinary tract infections were more frequent in the group of patients with PT-SPA infections (26.56%) (p < 0.01). Multivariate analysis was used to identify an injury on admission (OR = 3.089; 95% CI = 1.438-6.635; p = 0.004), administration of imipenem (OR = 15.027; 95% CI = 1.778-127.021; p = 0.013), meropenem (OR = 2.618; 95% CI = 1.030-6.653; p = 0.043), ciprofloxacin (OR = 3.380; 95% CI = 1.412-8.090; p = 0.006), vancomycin (OR = 4.294; 95% CI = 1.477-12.479; p = 0.007), piperacillin-tazobactam (OR = 4.047; 95% CI = 1.395-11.742; p = 0.010) as independent risk factors associated with PT-RPA infection.
In hospitalized patients, the risk of PT-RPA infections is associated with previous administration of imipenem, meropenem, ciprofloxacin, vancomycin, piperacillin-tazobactam, and the presence of injury on admission.
Kidney transplantation offers better quality of life in comparison to patient dialysis. Patients with endogenous creatinine clearance 30 mL/min/1.73m2 are introduced into the kidney transplant ...program. Every patient should be assessed for a degree of eligibility for the kidney transplant procedure. Basic principles of eligibility assessment include: patient education, assessment of patient's motivation level, medical risk assessment, as well as evaluation of psychosocial status and the level of family support. Medical risk assessment involves establishing the etiology of the primary kidney disease, cardiovascular status assessment, viral status assessment, risk assessment for renal graft thrombosis, screening for early malignancy detection, assessment of mineral metabolism and bone tissue disorders, and immunological risk assessment. Identification of patients with highest degree of kidney transplant eligibility shall decrease morbidity and mortality, reduce medical costs and improve the quality of life for these patients.
Pegylated interferon alfa plus ribavirin protocol is currently considered the most efficient hepatitis C treatment. However, no evidence of costs comparison among common viral genotypes has been ...published.
We aimed to assess core drivers of hepatitis C medical care costs and compare cost effectiveness of this treatment among patients infected by hepatitis C virus with genotypes 1 or 4 (group I), and 2 or 3 (group II).
Prospective bottom-up cost-effectiveness analysis from societal perspective was conducted at Infectious Diseases Clinic, University Clinic Kragujevac, Serbia, from 2007 to 2010. There were 81 participants with hepatitis C infection, treated with peg alpha-2a interferon plus ribavirin for 48 or 24 weeks. Economic data acquired were direct inpatient medical costs, outpatient drug acquisition costs, and indirect costs calculated through human capital approach.
Total costs were significantly higher (P = 0.035) in group I (mean ± SD: 12,751.54 ± 5,588.06) compared to group II (mean ± SD: 10,580.57 ± 3,973.02). In addition, both direct (P = 0.039) and indirect (P < 0.001) costs separately were significantly higher in group I compared to group II. Separate comparison within direct costs revealed higher total cost of medical care (P = 0.024) in first compared to second genotype group, while the similar tendency was observed for total drug acquisition (P = 0.072).
HCV genotypes 1 and 4 cause more severe clinical course require more care and thus incur higher expenses compared to HCV 2 and 3 genotypes. Policy makers should consider willingness to pay threshold differentially depending upon HCV viral genotype detected.
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