[Criteria for the optimal use of interleukin-6 receptor blockers in patients with COVID-19].

AIM: To determine the criteria for the optimal use of IL-6 receptor blockers in patients with COVID-19 community-acquired pneumonia based on predictors of adverse outcomes. MATERIALS AND METHODS: The single-center, non-randomized prospective study included 190 patients with community-acquired pneumonia caused by coronavirus 2 between the beginning of March and the end of May 2020. Of these, 89 patients received tocilizumab and 101 patients received sarilumab. The study inclusion criterion for the patient was indications for initiating therapy with one of the inhibitors of IL-6 receptors (anti-IL-6R) according to the Interim guidelines (versions 4 and 5). The exclusion criterion was the need to re-prescribe genetically engineered biological therapy (GEBT). The severity of the patient's condition was assessed according to the early warning score (NEWS2), the volume of lung tissue lesions was assessed according to computed tomography (CT). Laboratory monitoring included counting the absolute (abs) number of lymphocytes, serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), D-dimer, lactate dehydrogenase, fibrinogen. Statistical data processing was conducted by nonparametric methods using the IBM SPSS Statistics V-22 software. RESULTS: The phenotype of a patient with a negative outcome prognosis was described: a male patient over 50 years of age with aggravated premorbid background (with cardiovascular diseases, obesity and/or chronic renal disease), lung lesion CT 34, saturation less than 93% upon inhalation of atmospheric air, persisting for 2448 hours after GEBT. According to the blood test, lymphopenia was below 1000 U/L and CRP levels were above 50 mg/L. The laboratory parameters and clinical picture of the patient progressively worsened after 911 days of illness, regardless of the use of Anti-IL-6R. The features of patients monitoring when administering IL-6 receptor blockers have been determined. CONCLUSION: IL-6 receptor blockers should be administered to patients hospitalized with severe COVID-19 before the development of hyperinflammatory reactions. The optimal "therapeutic window" is 78 days of illness.

Treatment and in-Hospital Overall Survival in Hematological Patients with Grade 4 Neutropenia and Coronavirus Infection

Background: According to published data, the risk of coronavirus infection (COVID-19) in patients with malignancies is 5 times higher than in those without malignancies. Objective: To evaluate in-hospital overall survival in hematological patients with grade 4 neutropenia associated with coronavirus infection. Patients: This study was conducted from April 24, 2020 to June 17, 2021 in the Department of Hematology of Moscow City Clinical Hospital No. 52 (Russian Federation) and included 76 hematological patients with grade 4 neutropenia and coronavirus infection (aged 18-91 years): • 40 patients with acute leukemias (32 with AML, 8 with ALL): 22 men with a median age of 54 years (interquartile range (IQR) 43-60) and 18 women with a median age of 61 years (IQR 56-70) and • 36 patients with lymphoproliferative diseases (mostly with aggressive non-Hodgkin's lymphomas): 13 men with a median age of 57 years (IQR 40-68) and 23 women with a median age of 63 years (IQR 35-75). All patients were brought in by ambulance from other hospitals where they had received a course of combination chemotherapy interrupted due to coronavirus infection. Results: Most pts had moderate to severe lung disease (CT severity scores were 2, 3, and 4 in 29 (38.2%), 17 (22.5%), and 8 (10%) patients, respectively);55% of patients had high C-reactive protein and procalcitonin (above 0.5 ng/mL);lactate dehydrogenase (mean 395.7 U/L) and D-dimer (mean 2533.8) levels were significantly elevated. Patients had a higher NEWS score (mean 8) and a high Charlson comorbidity index score (mean 5). Interleukin-6 and IL-1b blockers were used as pathogenetic therapy to control hypercytokinemia. Taking into account grade 4 neutropenia, the dose of interleukin blockers was reduced. In order to prevent thromboembolic complications, low molecular weight heparins were used at therapeutic doses (with anti-Xa activity monitoring). Oxygen was administered in patients with clinical signs of respiratory failure (oxygen insufflation via nasal cannulas or mask). Patients with progressive respiratory failure were transferred to intensive care unit. In order to improve humoral immune response (due to low SARS-CoV-2 IgG antibody titers), 43.4% of patients were administered replacement therapy with pathogen-reduced fresh-frozen COVID-19 convalescent plasma. This led to a pronounced IgG increase in 7 patients only. Antifungal treatment was used in 54% of cases. Empirical antibacterial treatment for community-acquired pneumonia was administered, including inhibitor-protected aminopenicillins and respiratory fluoroquinolones (as 1st line treatment), upfront antibacterial treatment for neutropenic fever (2nd line), and targeted antibacterial treatment (3rd line). • In the acute leukemia group, 25 (63%) patients died during hospital treatment and 15 (37%) subjects survived;the median overall survival was 15 days (95% CI 15-22) (Fig. 1). • In the lymphoproliferative disease group, the numbers of deaths and survivals were 22 (61%) and 14 (39%), respectively, and the median overall survival was 25 days (95% CI 11-32) (Fig. 2). The median follow-up was 24 days. Conclusions: Coronavirus infection associated with severe neutropenia (caused by tumor progression and/or combination chemotherapy) is a significant adverse factor for overall survival in patients with hematological malignancies. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Baricitinib in the treatment of patients with COVID-19: A review of international data and analysis of clinical results in the Russian Population

The effects of baricitinib, a selective reversible inhibitor of Janus kinase 1 and 2, in the treatment of COVID-19 are associated with different aspects of pathogenesis - inhibition of viral endocytosis, reduction of excessive inflammatory response, and mitigation of vascular and pulmonary damage, which is a strong rationale for using baricitinib to treat patients with COVID-19. In the period from April to May 2020, City Clinical Hospital No. 52 obtained clinical experience of baricitinib clinical use in the therapy of 113 patients with COVID-19:58 (51%) women and 55 (49%) men, whose average age was 57±12.6 years old. Analysis of the results of using baricitinib showed that therapy with baricitinib against the background of standard pathogenetic therapy was found to be effective in 95 (84%) patients and ineffective in 18 (16%). Significant positive changes were shown in comparison with the baseline level of the following indicators: body temperature (from 37.2+0.8°C to 36, ±0.68°C, P=0.000), blood oxygen saturation (from 95.5±3.0% to 96.5±2.2%, P=0.011), C-reactive protein (from 46.1±48.0 mg/L to 33.5±43.7 mg/L, P=0.010), National Early Warning Score (NEWS) (from 1.7±1.3 to 1.1±1.2, p=0.001).From the safety point of view, patients showed a slight decrease in the average value of the number of neutrophils - from (3.1±1.4)xl09 to (3.0±2.0)xl09 and lymphocytes - from (1.8±0,9) x 109 to (1.7±0.9) x 109, as well as minimal multidirectional changes in the mean values of transaminase activity - alanine aminotransferase changed from 33.9±23.6 U/L to 34.9±47.5 U/L, aspartate aminotransferase - from 40.6±49.0 U/L to 38.5±25.5 U/L. In general, the results obtained within the experience of the clinical use of baricitinib in 113 Russian patients with COVID-19 are consistent with the available data from foreign clinical studies and confirm the efficacy and safety of baricitinib. © Team of Authors, 2021.

COVID-19 management: Who needs electrocardiographic monitoring and why

Chloroquine phosphate and hydroxychloroquine sulfate are used for treatment and prevention of complications associated with COVID-19. The use of these drugs has the potential to cause QT interval prolongation. The combination of antimalarial drugs with fluoroquinolones and macrolides increases the risk of rhythm disturbance. Objective. Based on analysis of own clinical data to determine the QTc-interval value for correction of monitoring of patients with COVID-19-associated extra-hospital pneumonia during antiprotozoic course in combination with antibacterial agents with cardiovascular toxicity (macrolide or fluoroquinolone). Material and methods. A single-center non-randomized prospective study to evaluate the safety of therapy in 98 patients with COVID- 19 community-acquired pneumonia. Patients were divided into two subgroups: patients with (n=39) and without (n=59) cardiovascular diseases. Results. QTc prolongation from baseline (360 ms, from 350 to 380) was observed on fifth (390 ms, from 360 to 400;p=0.003) and 10th (400 ms, from 390 to 430;p=0.005). In patients with cardiovascular diseases, QTc prolongation from baseline was detected only on the 10th day (360 ms, from 340 to 410 ms vs 400, from 370 to 450 ms;p=0.03). Conclusions. Co-administration of hydroxychloroquine sulfate with fluoroquinolones or macrolides in patients with COVID- 19 was not associated with severe QTc prolongation or arrhythmias. © 2020, Media Sphera Publishing Group. All rights reserved.

Maintenance oncohematological patients and new coronavirus infection: Experience of the City Clinical Hospital NO 52

Justification. Oncological diseases, along with diabetes, hypertension, cardiovascular and chronic obstructive pulmonary diseases, are associated with severe course and worst prognosis of the new coronavirus infection - COVID-19. Due to the limited number of the international studies and the lack of the domestic publications on the analysis of the course of COVID-19 in patients with oncohematological pathology and the patient management tactics, this work seems extremely topical. Materials and methods. 24.04.2020-31.05.2020, 110 patients with oncohematological pathology associated with new coronavirus infection were observed on the basis of the hematology service of City Clinical Hospital No 52: 59 women and 51 men, mean age 58 (18-90) years. Results. Currently, 24 (22%) patients among 110 are continuing treatment. The outcome of the disease is observed in 86 (78%) patients: 50 (58%) patients were discharged from hospital with complete or partial resolution of pneumonia, 36 (42%) of the 86 patients died. The groups did not differ in gender. The median age was higher in the group of deceased patients (66 vs. 54 years in patients who had a favorable outcome after COVID-19). The somatic status ECOG 3-4 was an independent predictive factor determining the adverse outcome of the disease. The third part of the patients from the group with a fatal cases due to a severe condition in the debut of the disease immediately were hospitalized in the intensive care unit (ICU), 2 (6%) of them had died within the first day. Disposition, according to the nosology showed a significant predominance among patients with an adverse outcome associated with acute leukemia (18% vs 39%). Patients with resistant course of hemoblastosis accounted for 50% of deceased patients. Severe form of the course of COVID-19 infection was twice as frequently (46% vs 84%) among patients with an adverse outcome of the disease, that was associated with both the initial more severe group of patients (33% were hospitalized in the ICU), and less curability of pneumonia against the background of the adverse prognostic factors: the older age group, the predominance of patients with acute leukemia and resistant course of oncohematological diseases. Specific anticancer therapy and COVID-19 therapy were comparable in both groups. Conclusions. Identification of new coronavirus infection against a backdrop of oncohematological disease is associated with a severe course of COVID-19 and high death rate - 42%. According to the preliminary obtained results, the adverse prognostic factors of COVID-19 in patients with oncohematological diseases include: elderly age, the poor somatic status (ECOG 3-4), relapse or progression of hemoblastosis and nosological affiliation to acute leukemia. © 2020 Journal of Modern Oncology. All rights reserved.

Cardiac damage in patients with COVID-19 coronavirus infection [Russian]

The article reviews studies that confirm the relationship of a negative prognosis with the presence of risk factors for cardiovascular complications during respiratory infections, including novel coronavirus infection COVID-19. The article presents the relevant research results that provide evidence on the myocardial damage in coronavirus infection. We present a clinical case of a patient with confirmed diagnosis of COVID-19 and severe viral myocarditis, verified by histological and immunohistochemical studies. Copyright © 2020 All-Russian Public Organization Antihypertensive League. All rights reserved.