ABSTRACT
Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Objective. To analyze the efficacy of levilimab in patients with COVID-19 to optimize proactive anti-inflammatory therapy. Patients and methods. This single-center retrospective observational controlled study included 75 COVID-19 patients with a mean age of 58.6 years who received intravenous (71%) or subcutaneous (29%) levilimab at a dose of 324 mg on day 9 of the disease [range: 7.0–12.0 days]. Ten patients (14%) additionally received tocilizumab, whereas 14 participants (19%) received only levilimab without dexamethasone. The control group (received no levilimab) included 29 matched patients. The levels of C-reactive protein (CRP), ferritin, fibrinogen, creatine phosphokinase (CPK), D-dimer, as well as lymphocyte and white blood cell (WBC) counts were measured daily. The percentage of lung damage was assessed using computed tomography (CT) at baseline and later in dynamics. The primary endpoint was patient's transfer to the intensive care unit (ICU). Statistical analysis was performed using the Statistica v. 12 software (StatSoft, USA);the risk of transfer to ICU was evaluated using the Kaplan-Meier cumulative proportional risk method and Cox proportional hazards model by calculating relative risks with a 95% confidence interval (RR [CI]). The dynamics of patients' status and its association with the route of levilimab administration was evaluated using a seven-point scale (seven-category scale) approved by the World Health Organization. Results. No lethal outcomes were registered in this study. Levilimab reduced the risk of transfer to the ICU;significant covariates included obesity (RR = 11.09 [1.29–95.72]) and percentage of lung damage on CT scans (RR = 1.06 [1.01–1.13]). The target group for levilimab therapy should include patients with moderate COVID-19 before day 10 of the disease, who have not yet received corticosteroids (CSs), with a maximum body temperature of ≤38.5°C, lung damage <40% on CT at the time of therapy initiation, and CPK <300 U/L. Levilimab therapy is more beneficial for patients with diabetes mellitus, obesity, severe arterial hypertension, and stomach and duodenal ulcers. Intravenous administration of levilimab at a dose of 324 mg is optimal for a reliable prevention of excessive cytokine release. Levilimab demonstrated equivalent positive effects both together with CSs, and when used alone. Levilimab without CSs alleviated hyperglycemia and normalized WBC count. The following laboratory parameters were found to be most important for the decision on levilimab initiation and further control of treatment efficacy: absolute lymphocyte count, CRP, fibrinogen, and CPK. Levels of lactate dehydrogenase, ferritin, platelets, D-dimer did not provide any reliable information on the mitigation of systemic inflammation.
ABSTRACT
Objective. To analyze polymorphisms of genes involved in hemostasis among patients with coronavirus disease 2019 (COVID 19) to improve the diagnosis of coagulopathy and prognosis of COVID-19 severity. Patients and methods. We have examined 52 patients with COVID-19 aged 33 to 84 years. Of them, 30 individuals (Group 1) were hospitalized with extremely severe (1A) and severe (1B) disease, whereas 22 patients with mild and asymptomatic disease were treated in outpatient departments (group 2). We assessed allelic variants of genes associated with hemostasis dysfunction (including FGB, FII, FV, FVII, F13A1, PAI-I, Gp1a, and Gp3a) using genomic DNA isolated from peripheral blood leukocytes. Polymorphisms were detected by polymerase chain reaction. Data analysis was performed using the Statistica, version 12 (StatSoft, USA). To compare independent categorical variables, we constructed contingency tables, performed Pearson chisquare test with Yates correction, Fisher exact test, and calculated relative risk (RR) [CI]. Results. COVID-induced coagulopathy (CAC) was diagnosed in 16.7% of patients;risk of CAC was identified in 30% of patients;sepsis-induced coagulopathy (SIC) was observed in 3.3% of patients;none of study participants had disseminated intravascular coagulation (DIC). Hemostasis impairments were more common in group 1A (RR = 2.28 [1.16–4.48]). Only patients from Group 1 had mutations in the gene encoding prothrombin (FII) –6.9% (RR = 1.78 [1.40–2.28]);protective polymorphisms in the FVII gene were more common in patients from Group 2 (χ2 = 3.28, р = 0.046);the rs 5985 polymorphism in the F13A1 gene was more common in patients from Group 1 (RR = 1.73 [1.06–2.82]). Patients with extremely severe COVID-19 were more likely to have polymorphisms in the Gp1a gene (ITGA2) (RR =1.64 [1.05–2.56]) and F13A1 gene (χ2 = 2.67, р = 0.05), as well as homozygous mutation in the FII gene;they had no polymorphisms in the FVII gene (10976G→A). Thrombophilia, detected in 3 patients from Group 1, was a risk factor for thrombocytopenia (RR = 13.5 [3.56–51.23]), САС (RR = 9.0 [3.1–26.16]), and death (n = 4). The 4G allele (4G/4G, 4G/5G variants) in the PAI-I gene (rs 1799889), causing impaired fibrinolysis, was more frequently registered in patients with mild COVID-19 (91%) than in those with extremely severe COVID-19 (70%). It is possible that patients with extremely severe disease develop transient hyperfibrinolysis, which results in the transformation of local pulmonary COVID-19 into sepsis. Therefore, the 4G/4G and 4G/5G polymorphisms may have a protective role. © 2021, Dynasty Publishing House. All rights reserved.