[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].

BACKGROUND: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. AIM: To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. MATERIALS AND METHODS: Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. RESULTS: In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). CONCLUSION: The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

The informative value of CD3+CD4+ and CD3+CD8+ T-cell count and cHIS scale as predictors of severe COVID-19 when using interleukin-6 receptor blockers in the in-hospital setting.

BACKGROUND: Clinical and laboratory signs of hyperinflammatory response in COVID-19 may serve as prognostic markers of the disease scenario. In real-world practice, there is an unmet need to determine the optimal timing of identifying predictors of SARS-CoV-2 adverse outcomes in the context of patient stratification to improve the effectiveness of anti-IL-6R therapy. Lymphopenia has a high informative value for the adverse prognosis of the COVID-19 course; however, the informative value of CD3+CD4+, CD3+CD8+ T-cell count remains questionable. In addition to lymphocyte phenotyping, a six-criterion additive scale (cHIS) was used in the study. AIM: To study the informative value of CD3+CD4+, CD3+CD8+ T-cell phenotyping and cHIS scale as predictors of severe COVID-19 when using IL-6R blockers. MATERIALS AND METHODS: A single-center, bi-directional study included 179 patients with SARS-CoV-2-induced community-acquired pneumonia with severe acute inflammation and progressing respiratory failure. Data were obtained from electronic patient records. Anti-IL-6R was administered in addition to standard therapy in the cohorts. The following disease outcomes were used to determine the informative value of the studied parameters: mortality and hospital discharge. Inflammatory markers were measured before and after administering anti-IL-6R, followed by monitoring. Statistical analysis was performed using SPSS (version 25.0). The quantitative indices were described using the median and interquartile range. Quantitative indices were compared using nonparametric methods: Mann-Whitney U-test, Kruskal-Wallis test. The groups were compared by qualitative characteristics using Pearson's chi-square test. Correlation analysis of quantitative indicators was performed using Spearman rank correlation. For additional analysis of the cHIS scale, odds ratio and decision tree methods were used. Differences were considered statistically significant at р≤0,05. RESULTS: Immunophenotyping of lymphocytes as a predictor of the severe SARS-CoV-2 requires further research. The cHIS scale may be implemented in routine clinical practice due to its high predictive value. A cHIS score of ≥2 on the first day of admission is a critical threshold for intensification and revision of therapy. The prognosis with cHIS is logically relevant in the first three days of hospitalization. CONCLUSION: The main result of the study is the definition of target groups of patients with community-acquired SARS-CoV-2 pneumonia for the IL-6R-blockers, considering the timing of their effective use in real clinical practice.

[Efficacy and safety of regdanvimab in patients with mild/moderate COVID-19 and high risk of progression of the disease: a retrospective study in a short-term stay unit].

BACKGROUND: The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease. AIM: To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit. MATERIALS AND METHODS: Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. INCLUSION CRITERIA: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). EXCLUSION CRITERIA: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR. STATISTICS: Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the KaplanMeier method. The significance level was determined at p0.05. RESULTS: A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study. CONCLUSION: In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.

[Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients' treatment].

AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.

[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.

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.