[Informativeness estimation for the main clinical and laboratory parameters in patients with severe COVID-19].

AIM: To conduct a retrospective assessment of the clinical and laboratory data of patients with severe forms of COVID-19 hospitalized in the intensive care and intensive care unit, in order to assess the contribution of various indicators to the likelihood of death. MATERIALS AND METHODS: A retrospective assessment of data on 224 patients with severe COVID-19 admitted to the intensive care unit was carried out. The analysis included the data of biochemical, clinical blood tests, coagulograms, indicators of the inflammatory response. When transferring to the intensive care units (ICU), the indicators of the formalized SOFA and APACHE scales were recorded. Anthropometric and demographic data were downloaded separately. RESULTS: Analysis of obtained data, showed that only one demographic feature (age) and a fairly large number of laboratory parameters can serve as possible markers of an unfavorable prognosis. We identified 12 laboratory features the best in terms of prediction: procalcitonin, lymphocytes (absolute value), sodium (ABS), creatinine, lactate (ABS), D-dimer, oxygenation index, direct bilirubin, urea, hemoglobin, C-reactive protein, age, LDH. The combination of these features allows to provide the quality of the forecast at the level of AUC=0.85, while the known scales provided less efficiency (APACHE: AUC=0.78, SOFA: AUC=0.74). CONCLUSION: Forecasting the outcome of the course of COVID-19 in patients in ICU is relevant not only from the position of adequate distribution of treatment measures, but also from the point of view of understanding the pathogenetic mechanisms of the development of the disease.

Predictive Value of Specific Cytokines for Lethal Covid-19 Outcome

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.

Predictive Value of Specific Cytokines for Lethal Covid-19 Outcome

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.

Diagnostics and antimicrobial therapy of the infections caused by multiresistant microorganisms (update 2022)

Strains of microorganisms characterized by resistance to antimicrobial drugs used in medical organizations continue to spread In most regions of the world including Russia. It is clear that it affects both the effectiveness of antimicrobial therapy and tactics and strategy of its use not only in adults patients but also in children. The pandemic of coronavirus infection, in addition, highlighted the growing problems in treatment of invasive mycoses, the dose adjustment of antibiotics during sorption and dialysis therapy methods. These circumstances made it necessary to make adjustments to Guidelines on Diagnostics and Antimicrobial Therapy of Infections Caused by Multiresistant Strains of Microorganisms, which were prepared by a group of leading Russian experts in 2020 [1]. The submitted version of the recommendations was approved on 25.03.2022 at a joint meeting of the working group with representatives of public organizations: Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), and NGO Russian Sepsis Forum. These recommendations reflect an interdisciplinary consensus opinion on approaches to the diagnosis and antimicrobial therapy of infections caused by multiresistant microorganisms. They are based on data from publications obtained from randomized trials as well as based on international clinical guidelines with a high degree of evidence. It is rational to use the Guidelines for determining the tactics of empirical and etiotropic therapy of the most severe infections. © 2022 by the authors.

Cytokine patterns of fatal hyperinflammatory conditions, caused by secondary hemophagocytic lymphohistiocytosis, bacterial sepsis and COVID-19

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.

Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study.

BACKGROUND: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. METHODS: The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. RESULTS: Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone). CONCLUSIONS: Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.

The role of ferritin in assessing COVID-19 severity

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.

Microcirculation Disorders in Patients with Severe COVID-19

Impaired microcirculation due to endothelial dysfunction in COVID-19 is considered to be the most important link in the pathogenesis of this disease. However, due to the complexity of its instrumental assessment in critically ill patients, the data available in the literature on specific manifestations of endothelial dysfunction are very contradictory. The objective: to determine the most characteristic capillaroscopic signs of microvascular disorders and to assess the state of microcirculation regulation in patients with severe COVID-19. Subjects and Methods. When admitted to the intensive care unit, 60 patients with COVID-19 and 12 patients with chronic cardiovascular pathology without COVID-19 (Comparison Group) were examined. All patients underwent microscopy of the microcirculatory bed of finger nail bed;the following parameters were assessed: diameters of the venous, arterial and transitional parts of capillaries, height of capillary loops, density of capillaries per 1 mm of the length of the perivascular zone, the average linear velocity of capillary blood flow (LVCBF), and thickness of the perivascular zone. The presence of avascular zones, the number of capillaries in the visualized field with circulating aggregates in the lumen, and the shape of capillaries were taken into account. In addition, an occlusion test using laser Doppler flowmetry was performed in 32 patients with COVID-19. The maximum post-occlusive increase in blood flow at the moment of cuff deflation was assessed, as well as changes in the mean value of post-occlusive blood flow relative to the baseline within 3 minutes after cuff deflation. Results. In 53 (88.3%) patients with COVID-19, abnormalities corresponding to chronic microcirculatory changes in the form of predominance of pathological capillary forms were detected. Microaggregates in the lumen of capillaries and decreased linear velocity of blood flow were revealed in 100% of cases. When comparing groups of patients with different outcomes, statistically significant differences were revealed between the LVCBF parameters (in the survivors - 354.35 ± 44.78 pm/sec, in the deceased - 278.4 ± 26.59 pm/sec), as well as between the values of the perivascular zones thickness (95.35 ± 15.96 microns versus 159.93 ± 19.90 microns). The results of the post-occlusion test revealed a significant difference between the groups in terms of the maximum post-occlusion gain (39.42 ± 3.85 BPU in the group with a favorable outcome, 27.69 ± 3.19 BPU in the group with an unfavorable outcome, 47.23 ± 1.78 BPU in the control group). In both groups, there was no increase in this parameter relative to the initial blood flow. At the same time, in the control group, the average index of post-occlusive blood flow was higher than the initial level. Conclusions. Acute microcirculation disorders with decreased linear velocity of capillary blood flow, circulation of aggregates, increased thickness of the perivascular zone were detected in all patients with severe COVID-19 but especially in those with unfavorable outcomes. Vascular tone regulation disorders were manifested by the absence of reactive hyperemia in response to acute ischemia, as well as a decrease in maximal flow-induced increase. These changes fit into the concept of endothelial dysfunction. Signs of chronic microcirculation disorders in most patients increase the risk of severe COVID-19. © 2021 Editorial Department of Scientia Agricultura Sinica. All rights reserved.

Acute kidney injury in patients with the new coronavirus infection

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.

Changes in the levels of some cytokines when using blood purification in COVID-19 patients

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.

The Pavlov University experience in medical assistance for patients with the novel coronavirus infection: First results and lessons

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.

The informative value of proadrenomedullin in patients with severe COVID-19

The severe course of COVID-19 is characterized by a high level of inflammation which requires the use of additional diagnostic technologies to clarify the cause of it. The objective: To study the informational value of proadrenomedullin (PADM) in patients with the novel coronavirus infection of COVID-19. Subjects and methods. The retrospective study included 37 patients (n = 37) diagnosed with severe viral pneumonia (SARS-CoV2) who were treated in the intensive care unit of Pavlov First Saint Petersburg State Medical University. To assess the significance of PADM as a biomarker of bacterial infection, patients were divided into two groups: The group of patients with viral pneumonia without sepsis (n = 24) and the group of those who developed sepsis and septic shock complicating the course of the new coronavirus infection (n = 13). PADM was assessed as a criterion for the severity of the disease in the groups of deceased (n = 19) and survivors (n = 18). Data were statistically processed in the computer mathematics system R, version 3.6.2, the prognostic significance of PADM was assessed using linear regression. Results. The median PADM in the group without sepsis was higher than the reference value - 1.1 (0.5;4.3) nmol/L, in patients with sepsis that complicated the course of viral pneumonia - 2.8 (1.1;5.7) nmol/L (p = 0.0019). Significant differences were revealed between the baseline levels of PADM in patients with different outcomes: in the surviving group, the median was 0.99 (0.5;3.14) nmol/L, and in the group of deceased - 2.70 (0.94;5.86 ) nmol/L. In surviving patients, the changes in PADM levels had a linear distribution throughout the entire period of stay in the intensive care unit. In deceased patients, within 20 days before death, PADM tended to grow significantly and reached its maximum by the time of the outcome. Conclusion. The assessment of the PADM blood level can be used to clarify the addition of a bacterial infection in patients with pneumonia caused by the SARS-CoV2 virus. The study of changes in its level makes it possible to objectify the prediction of the course of COVID-19 - favorable or unfavorable. Data accumulation is required to clarify specific PADM values that predict the outcome in COVID-19 patients. © 2020 Messenger of Anesthesiology and Resuscitation. All rights reserved.

Catastrophic antiphospholipid COVID-19 syndrome

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.

Evaluation of microcirculation disorders in patients with severe COVID-19 by nail bed capillaroscopy

Microcirculation disorders caused by thrombosis are the most important factor determining the pathogenesis of organ damage in severe COVID-19 including the absence of obvious macrohemodynamic instability. However, there are very few publications demonstrating the results of intravital visualization of changes in the microcirculation system in this disease. The objective: to assess the state of microcirculation in patients with viral pneumonia associated with COVID-19 using nail bed microscopy. Subjects and methods. Eleven patients with COVID-19 were examined;they were admitted to the intensive care unit due to progressing acute respiratory failure. Vital microscopy of the microcirculatory bloodstream in the fingers' nail bed was performed by admission and over time. When assessing microcirculation, the presence of aggregates in the lumen of capillaries and avascular zones, and the linear velocity of blood flow were taken into account. The results were summarized taking with the outcome consideration (6 people recovered, 5 died). Results. Microcirculation disorders were objectively confirmed in all patients. In 100% of cases, microaggregates were detected in the capillary lumen. The values of the mean linear velocity of capillary blood flow turned out to be extremely variable. However, the values of the maximum linear velocities of capillary blood flow in the patients who subsequently died were significantly lower versus survivors (190 μm/sec (135.5;237) and 387 μm/sec (329.3;407.5), p = 0.018). The irregularity of blood flow in the visualized field was revealed: when the value of the maximum linear velocity in some capillaries was less than 180 µm/sec, in others, disturbances in the form of pendulum-like movement were already noted. Further slowing down of the blood flow velocity led to the development of stasis and the formation of avascular zones. Conclusion. Impaired microcirculation (decreased blood flow rate in the capillaries, the presence of microaggregates and a lower number of perfused capillaries in the form of avascular zones) develops in all patients with severe COVID-19. © 2021 New Terra Publishing House. All rights reserved.