[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.

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.

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.