ABSTRACT
In our study, we aimed to evaluate the significance of specific cytokines in blood plasma as predictive markers of COVID-associated mortality. Materials and methods. In plasma samples of 29 patients with PCR-confirmed COVID-19 we measured the concentrations of 47 molecules. These molecules included: interleukins and selected pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNalpha2, IFNgamma, TNFalpha, TNFbeta/Lymphotoxin-alpha(LTA));chemokines (CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROalpha, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine);anti-inflammatory cytokines (IL-1Ra, IL-10);growth factors (EGF, FGF-2/FGF-basic, Flt-3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGFAB/BB, TGFalpha, VEGF-A);and sCD40L. We used multiplex analysis based on xMAP technology (Luminex, USA) using Luminex MagPix. As controls, we used plasma samples of 20 healthy individuals. Based on the results, we applied Receiver Operating Characteristic (ROC) analysis and Area Under Curve (AUC) values to compare two different predictive tests and to choose the optimal division point for disease outcome (survivors/non-survivors). To find optimal biomarker combinations, we as used cytokines concentrations as dependent variables to grow a regression tree using JMP 16 Software.Results. Out of 47 studied cytokines/chemokines/growth factors, we picked four pro-inflammatory cytokines as having high significance in evaluation of COVID-19 outcome: IL-6, IL-8, IL-15, and IL-18. Based on the results received, we assume that the highest significance in terms of predicting the outcome of acute COVID-19 belongs to IL-6 and IL-18. Conclusion. Analyzing concentrations of IL-6 and IL-18 before administering treatment may prove valuable in terms of outcome prognosis. Copyright © Arsentieva N.A. et al., 2022.
ABSTRACT
In our study, we aimed to evaluate the significance of specific cytokines in blood plasma as predictive markers of COVID-associated mortality. Materials and methods. In plasma samples of 29 patients with PCR-confirmed COVID-19 we measured the concentrations of 47 molecules. These molecules included: interleukins and selected pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNalpha2, IFNgamma, TNFalpha, TNFbeta/Lymphotoxin-alpha(LTA));chemokines (CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROalpha, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine);anti-inflammatory cytokines (IL-1Ra, IL-10);growth factors (EGF, FGF-2/FGF-basic, Flt-3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGFAB/BB, TGFalpha, VEGF-A);and sCD40L. We used multiplex analysis based on xMAP technology (Luminex, USA) using Luminex MagPix. As controls, we used plasma samples of 20 healthy individuals. Based on the results, we applied Receiver Operating Characteristic (ROC) analysis and Area Under Curve (AUC) values to compare two different predictive tests and to choose the optimal division point for disease outcome (survivors/non-survivors). To find optimal biomarker combinations, we as used cytokines concentrations as dependent variables to grow a regression tree using JMP 16 Software.Results. Out of 47 studied cytokines/chemokines/growth factors, we picked four pro-inflammatory cytokines as having high significance in evaluation of COVID-19 outcome: IL-6, IL-8, IL-15, and IL-18. Based on the results received, we assume that the highest significance in terms of predicting the outcome of acute COVID-19 belongs to IL-6 and IL-18. Conclusion. Analyzing concentrations of IL-6 and IL-18 before administering treatment may prove valuable in terms of outcome prognosis. Copyright © Arsentieva N.A. et al., 2022.
ABSTRACT
Introduction. In severe cases of coronavirus disease 2019 (COVID-19) pulmonary infiltration is accompanied by cytokine storm syndrome (CSS) development. Besides COVID-19, CSS can be triggered by the range of pathologies, which include hemophagocytic lymphohistiocytosis (sHLH) and septic shock (SS). The aim of this study was to compare immunological profiles in fatal cases of COVID-19, sHLH and SS. Material and methods. Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17A, IL-18, IFN-γ, TNF-α, procalcitonin, neopterin, ferritin with percent of glycosylated fraction (% GF) were measured in 37 COVID-19 fatal cases, collected during 2020 year prospectively;and in 39 sHLH and 47 SS fatal cases, collected within 2018–2019 years retrospectively. Comparison groups also included 194 non-fatal COVID-19 cases and 20 healthy donors, collected during 2020 year. Cytokine concentrations, procalcitonin and neopterin were measured by enzyme-linked immunosorbent assay;the ferritin level was determined by the turbidimetry method. The percent of glycosylated ferritin fraction (% GF) was calculated by the modified method of M. Worwood et al. Results. Deceased patients with COVID-19 had higher IL-6, IL-8, IL-10, IL-18, procalcitonin median levels compared to the survived. Meanwhile IL-8, IL-18, IFN-γ, TNFα and ferritin concentrations were significantly lower in deceased COVID-19 patients compared to sHLH and SS. The levels of IL-6 and procalcitonin in fatal COVID-19 were comparable to SS, but significantly higher than in sHLH. Leucocytes were higher in COVID-19 compared to both SS and sHLH. Conclusion. Each fatal condition was accompanied by specific features of the cytokine profile: high IL-6 combined with low IFN-γ, TNFα in COVID-19;high IL-8, IL-6 with low IL-17A, IL-2 in SS;high IL-18, ferritin, IFN-γ with low IL-6, procalcitonin, % GF in sHLH.
ABSTRACT
Ferritin is one of the biomarkers requiring special attention;its blood level increases significantly especially in the severe course of COVID-19. Information on the effect of hyperferritinemia on the disease outcome is very contradictory as are the ideas about the causes of its development. The objective: to study the effect of hyperferritinemia on the disease outcome and analyse the possible causes of its development in severe COVID-19. Subjects and Methods. Data on 479 patients with severe course of coronavirus infection treated in intensive care units (ICU) were retrospectively analyzed. Of them, the proportion of patients with a favorable outcome (Group 1) was 51.0% (n = 241), and with an unfavorable outcome (Group 2) - 49.0% (n = 235). The following parameters were assessed: the levels of ferritin, C-reactive protein, fibrinogen, IL-6, IL-10, IL-18, procalcitonin, complement C5a, total, direct and indirect bilirubin, ALT, AST, and the blood level of lactate dehydrogenase (LDH). The changes of erythrocyte count and hemoglobin blood level were also monitored. In order to form a clear view of iron metabolism, free iron, transferrin, and myoglobin levels were assessed in several patients with high ferritin values (more than 1,500 pg/L). Results. In the unfavorable outcome, ferritin levels increase very significantly, reaching maximum by day 6 of patients' stay in ICU. The difference in the level of ferritin between the groups of survivors and deceased during this period is clear and significant (p = 0.0013). The association of ferritin values with the outcome is detected as early as day 1, but by day 4 it becomes highly significant (the cut-off point is 1,080 pg/l). No data have been obtained that would indicate the association of hyperferritinemia with impaired iron metabolism, the development of hepatic dysfunction, or cellular destruction. In contrast to survivors, those who died on day 6 had elevated IL-6 while C5a level remained unchanged. Conclusions. The rapid increase in ferritin blood levels to 1,000 pg/L or higher is an unfavorable prognostic sign indicating a high probability of a lethal outcome. When assessing genesis of hyperferritinemia in COVID-19, the crucial significance should be attributed to the cytokine storm rather than disorders of iron metabolism or hemotoxic effects of the virus. The persistent increase of ferritin level in blood during 4-6 days of stay in ICU should be considered as a reason to intensify anticytokine therapy. © 2021 Messenger of Anesthesiology and Resuscitation. All rights reserved.
ABSTRACT
The objective: to analyze the incidence of renal dysfunction in COVID-19 patients and assess the significance of systemic inflammation for its development. Subjects and methods: The analysis was performed basing on data of 3,806 patients with COVID-19 treated at the Pavlov State Medical University, 395 of them were admitted to the intensive care units (ICU). The criterion for establishing renal dysfunction (RD) is the increase in blood creatinine level above the upper limit of reference values (0.115 mmol/l). Patients with end-stage chronic kidney disease who needed to continue routine long-term dialysis were not included in the study. We analyzed the incidence of renal dysfunction, changes in blood levels of creatinine, urea, and electrolytes during 8 days. In addition, glomerular filtration rate, diuresis volume, levels of hematocrit, hemoglobin, LDH, CRP, ferritin, and procalcitonin were evaluated. Results. The frequency of RD among all patients was 19.0%, among patients in the ICU - 41.0%. In 79% and 81%, respectively, it was detected on the first day of hospitalization. The increase in the number of patients with RD and the aggravation of the existing dysfunction occurred after 6 days. At the initial stage of the disease, the manifestations of RD in most cases were not expressed even in those with an unfavorable course of the disease but the level of creatinine showed a weak but significant (p < 0.5) correlation with changes in CRP (r = 0.110), ferritin (r = 0.137), and procalcitonin (PCT, r = 0.418). The difference in the level of creatinine in patients with PСT level above and below 0.5 ng/ml was observed on the first day only;the value of this parameter returned to normal faster in the subgroup of patients whose procalcitonin level did not exceed 0.5 ng/ml. Conclusion. In case of the signs indicative of RD, it is advisable to distinguish between primary and secondary injury. In the first case, it is primarily due to systemic inflammation, in the second case it is caused by additional impact of other aggressive factors. This will make it possible to clarify the renal and non-renal indications for renal replacement therapy (RRT) in patients with COVID-19, and to evaluate the results adequately since the effectiveness of RRT at different stages of the disease cannot be the same. © 2021 Serbian Chemical Society. All rights reserved.
ABSTRACT
The use of high-Adsorption membrane hemofiltration in COVID-19 positive patients to reduce the severity of a cytokine storm is clearly beneficial but at the same time, there are no certain procedures for its practical use. The objective: To study the change in the levels of IL-6 and IL-18 in response to prolonged (24-72 hours) high-Adsorption membrane hemofiltration. Subjects and methods. We retrospectively analyzed the data on IL-6 and IL-18 levels and their changes in 69 patients who were COVID-19 positive and had different degrees of lung damage, they had received high-Adsorption membrane hemofiltration during their stay at the intensive care unit. The extent of lung lesions was the following: 4 people had CT-2, 44 people had CT-3, and 21 patients had CT-4. 18 patients had an unfavorable outcome of the disease. High-Adsorption membrane hemofiltration (Prismaflex) was used in the group of patients who had clinical signs of the rapid progression of the disease and also such laboratory findings as elevated values of C-reactive protein (above 100 mg/L), ferritin (more than 600 uu/L), and progression of lymphopenia. This intervention lasted for 24 hours at CT-2/3, and 48 hours at CT-4. The effluent dose was 30.0 6.4 ml/kg/h. The levels of IL-6, IL-18, and procalcitonin were tested before and after the completion of the intervention, and the difference between their concentration before and after high-Adsorption membrane hemofiltration was calculated. The potential association between received data (IL-6, IL-18, delta of IL-6, delta of IL-18) and degree of lung damage and outcomes was analyzed. Results. It was detected that the more the lungs were affected, the lower levels of IL-6 and IL-18 were and vice versa and this correlation was not associated with the use of tocilizumab (used in 44 people). The maximum decrease in the level of cytokines was observed in the group of patients with CT-2. There was a significant association between the delta of IL-6 (F = 6.69;p 0.05) and the outcome which was especially pronounced in people with a favorable outcome. Conclusion. As the inflammation progresses in the lungs, the levels of IL-6 and IL-18 decrease which may be a manifestation of the depletion of the cytokine storm. The use of prolonged high-Adsorption membrane hemofiltration (24-48 h) allows reducing the level of cytokines. The delta value reflects a decrease in IL-6 concentration, it significantly correlates with the outcome which indicates the importance of using this method in a continuous mode. © 2020 Geocarrefour. All rights reserved.
ABSTRACT
The constant mutation of the virus and the complicated epidemiological situation in other countries keep the probability of a third wave of the pandemic in the Russian Federation fairly high. It is important to summarize the gained experience as fast as possible to use it appropriately once it is needed. The objective: To analyze the specific parameters of care for critically ill patients with the novel coronavirus infection in Pavlov Multidisciplinary Medical Center. Subjects and methods. This is a result-based report on the work performed by the Infection Center, which was deployed twice in Pavlov Multidisciplinary Medical Center (from 28.04.2020 to 03.08.2020 and from 01.11.2020 to 15.03.2021). Totally, 3,830 patients with SARS-CoV-2 were managed (1,680 patients during the first deployment and 2,150 patients during the second one). In the preparatory period, the operation of the emergency department based on the inpatient emergency medical department (EMD) had been simulated to clarify its staff structure and the procedure for admission, examination, and treatment of patients. Here we compare the organizational approaches during the first and second waves of the pandemic and present the characteristics of the demographic data of the treated patients, the incidence of certain complications, and outcomes. Results. The overall lethality in the Center made 6.2%. Despite the experience gained in the first wave, the results of treatment during the second wave (autumn-winter) did not improve (5.7% died in the first wave and 6.7% in the second one). Lethality in ICU and EMD was 40.0% and 49.6%, in ICU only 38.5% and 46.9% respectively. A moderate lethality increase in ICU was due to the concentration of critically ill and most critically ill patients. There were 51.4% of patients with comorbidities and 53.5% were above 65 years of age. Refinement and differentiation of tasks performed by departments, simulation of the operation of the Center before opening made it possible to increase the throughput of the medical unit avoiding rush during admission and deterioration the quality of treatment. Conclusion. Certain aspects of the organization of medical care affect the performance of a multidisciplinary medical institution transformed into an infectious diseases hospital. The experience gained under such circumstances can be useful in other emergencies with a large number of victims and patients. © 2020 Geocarrefour. All rights reserved.
ABSTRACT
Thrombophilia, as well as multiple organ dysfunction, are typical manifestations of the severe new coronavirus infection that closely resemble the clinical signs of catastrophic antiphospholipid syndrome (CAPS). The objective: to assess whether catastrophic antiphospholipid syndrome is an essential manifestation of severe forms of COVID-19. Subjects and methods. 45 patients diagnosed with the new coronavirus infection (SARS-CoV-2) and a severe course of viral pneumonia (more than 3 points on the NEWS score by the admission, CT 3-4, oxygenation index below 100, the need for at least high-flow oxygen therapy). They were assessed for the development of CAPS due to signs of progressing organ dysfunction despite the ongoing intensive therapy, suspected pulmonary embolism and progressing venous thrombosis of a lower extremity or subclavian vein. It was an essential provision that they should have no signs of bacterial infection (blood procalcitonin should be below 0.5 μg/l). The antiphospholipid syndrome was diagnosed based on the detection of antibodies to β-2-glycoprotein in the blood (A/t β-2-GP1 IgGAM, A/t β-2-GP1 IgM, A/t β-2-GP1 IgG) and to cardiolipin (A/t CL IgM, A/t CL IgG) by ELISA tests. The course of the disease was monitored using other routine clinical (temperature, complete blood and urine counts) tests and blood panel tests reflecting the severity of the systemic inflammatory response (ferritin, CRP, interleukins 6 and 18), and the state of the hemostatic, respiratory, circulatory, liver and kidney systems. Results. Antiphospholipid antibodies (aAPL) moderately exceeding the reference values were detected in 9 out of 45 patients (20%), mainly due to IgA and IgM isotypes to β-2-glycoprotein and IgM isotype to cardiolipin. The assessment of the antibody titer in 5 patients over time (after 7 days) revealed a decrease, but it did not affect the outcome (four of them died). In 36 patients, some traces of aAPL were found that did not reach the lower limit of the norm, despite the uniformity of the clinical signs and similarity of biochemical parameters reflecting the severity of organ disorders. The absence of antibodies did not prevent the development of thrombotic complications (thrombosis of large vessels and pulmonary embolism in 5 patients). There were no other manifestations often associated with CAPS (thrombocytopenia, hemolytic anemia, decreased fibrinogen concentration in the blood). Conclusion. Catastrophic antiphospholipid syndrome is not inevitable in severe COVID-19 cases, however, it can develop as one of the manifestations of thrombophilia that occurs in such patients. © 2021 New Terra Publishing House. All rights reserved.