[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.

Vaccination against covid-19 for patients with primary immunodefi ciency and hereditary angioedema: The position paper of the Russian association of allergology, clinical immunology, and the national association of experts in primary immunodefi ciencies.

Since the end of 2019, the whole world has been suff ering from the Corona virus-19 (COVID-19) pandemic due to the potentially severe acute respiratory infection caused by the SARS-CoV-2 virus. To date, the infection has led to more than 4 million deaths worldwide, and>140 thousand deaths in Russia. Vaccination against COVID-19 plays a key role in stopping the pandemic. According to the existing experience in infection prevention, mass vaccination will reduce the virus's expansion and the risk of vaccine-resistant strains developing. In the context of COVID-19, the question of the feasibility and safety of vaccination for patients with primary immunodefi ciency and hereditary angioedema arises. The Russian Association of Allergists, Clinical Immunologists, and the National Association of Experts in Primary Immunodefi ciencies have developed and approved a position paper on the vaccination for patients with primary immunodefi ciency and hereditary angioedema against COVID-19. This position paper provides answers to key questions regarding vaccination for patients with these diseases.Copyright © 2020 Pharmarus Print Media License.

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.

Corynebacterium amycolatum infective endocarditis in a patient with severe COVID-19: a case report.

Objective. To present a case of successful treatment of a secondary bacterial infection caused by non-diphtheritic corynebacterium in a patient with severe COVID-19 and known beta-lactam intolerance. Materials and methods. A clinical case of infective endocarditis (IE) caused by Corynebacterium amycolatum in a 74-year-old patient hospitalized with severe COVID-19 is presented. Comorbidity (secondary immune deficiency due to active malignancy, chemotherapy courses;previous heart disease) and the need for immunosuppressive therapy were triggers for infection caused by a rare Gram-positive bacterium which is usually considered as clinically non-significant. The choice of empiric antimicrobial treatment was limited by the patient's history of beta-lactam intolerance. Results. A multidisciplinary approach to medical care of the patient and alertness to secondary infections helped to diagnose IE in a timely manner and to choose effective antimicrobial therapy. Combination therapy with vancomycin and amikacin helped to make blood flow free from infection. The further switch to oral doxycycline in outpatient settings resulted in the patient recovery from the infection. Conclusions. Under conditions of limited choice of drug therapy, it is critical to have access to modern microbiological diagnostics which make it possible to diagnose rare pathogens. A dialogue between treating physician and clinical pharmacologist helps to choose an empirical and targeted antimicrobial therapy with the best efficacy-safety ratio. There is a need to be alert to secondary infections, including those of atypical locations and courses and caused by rare or opportunistic pathogens.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

A rare case of CSU+CIndU resistant to systemic treatment with GCS and methotrexate initiated to Takayasu's disease

Case report Background: It is well known that chronic spontaneous urticaria (CSU) has an autoimmune etiology in 40% of cases. It is often comorbid with other autoimmune diseases and a wide spectrum of autoantibodies involved in the pathogenesis of CSU is discussed. Objective(s): We share a clinical case of a rare underline autoimmune disease with later onset of CSU and chronic induced urticaria (CIU). Case: A 38-year- old woman was admitted to the hospital with SARS-CoV- 2 infection. At the age of 22, she was diagnosed with Takayasu's disease involving the aorta, the common and external carotid artery, and the left subclavian artery. Surgical interventions were performed twice -angioplasty of the involved vessels, but in both cases restenosis of the affected arteries was observed. Regarding the underlying disease, the patient received 10 mg of methotrexate once a week and 20 mg of prednisone daily. Due to detailed history collection, the patient noted that for the last 4 months she has rashes, bright red in color, rising above the surface of the skin and accompanied by a strong burning and itching dominantly on the upper and lower extremities, trunk. Appearing every day spontaneously, they have a rounded shape (diameter of up to 40-50 mm). While liner scratching the rash has similar contour. Rash elements disappear within a few hours, do not leave traces. During the current hospitalization, a wheal element up to 40 mm in diameter was observed at the wrist area, stayed for a few hours. UAS-7 -42. According to examination: eosinophils 1000 cells/mcl (patient noticed that eosinophilia of the blood has happened before, an examination was conducted, helminthiasis and parasitosis were excluded), total IgE -more than 2000 IU/ml, antibodies to b2-glycoprotein were revealed. Freak test -negative, but the linear wheals were confirmed by retrospective photos. Result(s): In this clinical case, CSU occurs in combination with induced dermographic urticaria. This patient has extremely aggressive urticaria according to its frequency of occurrence despite therapy with systemic GCS and methotrexate. After recovery from coronavirus infection, further examination and consideration of the appointment of biologicals(anti-IgE) is planned.

Management of patients with primary immunodeficiency and COVID-19: The experience of a single reference center in Moscow, Russia

Case report: At present, the course of COVID-19 in patients with various PID remains a question of a major research interest. CVID and XLA are two major types of PID, prevalent in adult patients. We present a cohort observational study of patients with COVID-19 and PID admitted to our reference center. Case 1: 37 y.o., male, with CVID and agammaglobulinemia, developed COVID-19 symptoms since October 6, 2021. PCR test positive on October 7, 2021. On 7th day of the disease CT Scan revealed lung involvement -Pattern 1. Laboratory test: CRP 65g/L(10N), LDH-239U/ L, Lymph.1x109/L. At admission, virus-neutralizing Abs (nMAbs) were initiated. The temperature stayed subfebrile. On Oct. 18, the negative progression with the incidence of new foci on CT scan, accompanied by the decrease of Lymph. 0.9 x 109/L. IL-6R blockers were initiated. Despite the administration of nAbs in the early stages of the disease (Day 7), the patient experienced SARS-CoV- 2 breakthrough, which resulted in both clinical and laboratory parameters deterioration. Thus, patients with PID might be recommended a much earlier administration of nMAbs. Case 2: 36 y.o. male, with a agammaglobulinemia has experienced several COVID-19 episodes: Episode 1 (Dec. 2020) PCR (+), the patient had no lung lesion;2 (Jan 2021) PCR (-), CT scan showed ground-glass opacities and the crazy-paving pattern;3 (Feb 2021) PCR (positive), CT scan showed ground-glass opacities and the crazy-paving pattern, Chest CT revealed Pattern 2, tocilizumab and remdesivir were administrated;4 (Feb-Mar 2021) PCR (-), Chest CT showed viral pneumonia with variable findings (treatment against pneumocystis pneumonia);5 (Mar 2021) PCR (+), CT showed Pattern 2, Double force of a specific etiotropic treatment included remdesivir and COVID-globulin as iv infusion of to "accumulate" IgG antibodies against SARS-CoV- 2 and interrupt the virus persistence was successful and the elimination was finally reached. Conclusion(s): 25 patients with PID and COVID-19 were observed, 16% of them experienced several COVID-19 episodes.Depending on the PID type, several scenarios of COVID-19 in this cohort are being discussed:.

Effects of COVID-19 vaccination on chronic urticaria patients: First results of the UCARE COVAC-CU study

Background: Chronic urticaria (CU) is a common chronic inflammatory disease. Vaccination against viral infections including COVID-19 can induce increased CU disease activity. As of now, it is unclear how often CU exacerbations occur after COVID-19 vaccination. Method(s): COVAC-CU is an international, multicenter, observational, cross-sectional study of the global network of urticaria centers of reference and excellence (UCAREs). COVAC-CU evaluates the effects of COVID-19 vaccination in patients with CU including rates and risk factors of CU exacerbation. Here, we analyzed 1857 patients with CU who had received at least one COVID-19 vaccination. Data were collected via a questionnaire and retrieved from patient charts. Result(s): Of 1857 patients with CU (median age: 42 years;range: 18-91 years), 72.1% were female and 71.2%, 14.4% and 14.4% had chronic spontaneous urticaria, chronic inducible urticaria, or both, respectively. Most patients had received two doses of COVID-19 vaccine (79.1%), compared to one (9.7%), three (11%), or four (0.3%). Vaccine type included: BTN162b2 (58.4%;BioNTech/Pfizer), ChAdOx1 nCOV-19 (13.8%;AstraZeneca), BBIBP-CorV (8.2%;Sinopharm), Gam-COVID- Vac (8%;Sputnik), mRNA-1273 (5.3%;Moderna), and Ad26.COV 2.5 (4.7%;Janssen/J&J). Less than 10% of patients used premedication, and less than half of patients (44.4%) reported one or more adverse reactions after vaccination. The most common adverse reactions were local injection site reactions (29.6%), fatigue (19.7%), fever (19%), muscle pain (17.9%), headache (14%), and exacerbation of CU (15%). Severe allergic reactions/anaphylaxis were reported by 0.4% of CU patients. In almost all patients who experienced exacerbation of their CU, this occurred within one week after receiving the vaccine, i.e. after 1 to 12 hours (25.8 %), after 12 hours to 48 hours (31.1%) or after 2-7 days (37.9%). Conclusion(s): Most CU patients tolerate COVID-19 vaccination well;severe allergic reaction (anaphylaxis) rates were similar or lower than the self-reported rates reported in the general population. Exacerbation of urticaria was reported in one in five patients, mostly in a week after receiving the vaccine.

Corynebacterium amycolatum infective endocarditis in a patient with severe COVID-19: a case report

Objective. To present a case of successful treatment of a secondary bacterial infection caused by non-diphtheritic corynebacterium in a patient with severe COVID-19 and known beta-lactam intolerance. Materials and methods. A clinical case of infective endocarditis (IE) caused by Corynebacterium amycolatum in a 74-year-old patient hospitalized with severe COVID-19 is presented. Comorbidity (secondary immune deficiency due to active malignancy, chemotherapy courses;previous heart disease) and the need for immunosuppressive therapy were triggers for infection caused by a rare Gram-positive bacterium which is usually considered as clinically non-significant. The choice of empiric antimicrobial treatment was limited by the patient's history of beta-lactam intolerance. Results. A multidisciplinary approach to medical care of the patient and alertness to secondary infections helped to diagnose IE in a timely manner and to choose effective antimicrobial therapy. Combination therapy with vancomycin and amikacin helped to make blood flow free from infection. The further switch to oral doxycycline in outpatient settings resulted in the patient recovery from the infection. Conclusions. Under conditions of limited choice of drug therapy, it is critical to have access to modern microbiological diagnostics which make it possible to diagnose rare pathogens. A dialogue between treating physician and clinical pharmacologist helps to choose an empirical and targeted antimicrobial therapy with the best efficacy-safety ratio. There is a need to be alert to secondary infections, including those of atypical locations and courses and caused by rare or opportunistic pathogens. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

USING COVID-GLOBULIN IN COVID-19 TREATMENT

Under auspices of the Eurasian Association of Therapists (EUAT), a Council of Experts (COE) was organized to develop criteria for the timing of administration (day of illness onset) of COVID-globulin, dosing regimens and patient phenotypes depending on comorbid pathology to optimize indications and achieve maximum effectiveness of virus-neutralizing therapy. The need for COE creation is related to the lack of criteria based on large-scale evidence-based studies. That is why the working group of COE includes experts in all fields of internal medicine, in particular, transfusiology specialists. The COE activity was held with the participation of largest plasma transfusion centers for recuperative patients including Clinical Hospitals No. 40 and 52 of the Moscow City Government Department of Health, and the N. V. Sklifosovsky Institute of Emergency Medicine. Copyright © 2022 Authors. All rights reserved.

[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.

SARS-CoV-2-NEUTRALISING MONOCLONAL ANTIBODIES: MECHANISM OF ACTION AND RESEARCH RESULTS

The COVID-19 vaccination has become a way of effective prevention of the decease for most people globally. However, there is a cohort of patients who are not able to form a full-fledged immune response due to primary or secondary immunodeficiency conditions caused by genetic disorders, severe course of chronic diseases, due to their age or the use of drugs that suppress the immune response. The use of monoclonal viral antibodies for immunocompromised patients is the most efficient method of pre- and post-contact and even long-term prevention, as well as the treatment of coronavirus infection. Monoclonal antibodies are obtained from B-lymphocytes of patients recovered from COVID-19. As a result of further modification aimed at increasing of the efficiency and reducing the risk of unwanted phenomena in the use, the virus-neutralizing recombinant monoclonal antibodies of the IgG1 class were designed to implement preventive and therapeutic schemes for COVID-19. Treatment of a new coronavirus infection with drugs with direct etiotropic action is most effective when prescribing in the early stages of the disease, which is especially relevant in patients at risk for a severe/critical clinical course of the disease and can be performed as outpatient clinical procedures. The article analyzes the results of clinical studies of efficacy and safety of mono- and combined drugs of monoclonal antibodies to SARS-CoV-2 in patients with the new coronavirus infection, as well as potential possibilities for their use for the treatment of COVID-19 caused by the new SARS-CoV-2 strains with multiple mutations on the example of the Omicron strain.

[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.

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.

Vaccination against covid-19 for patients with primary immunodefi ciency and hereditary angioedema: The position paper of the Russian association of allergology, clinical immunology, and the national association of experts in primary immunodefi ciencies

Since the end of 2019, the whole world has been suff ering from the Corona virus-19 (COVID-19) pandemic due to the potentially severe acute respiratory infection caused by the SARS-CoV-2 virus. To date, the infection has led to more than 4 million deaths worldwide, and>140 thousand deaths in Russia. Vaccination against COVID-19 plays a key role in stopping the pandemic. According to the existing experience in infection prevention, mass vaccination will reduce the virus’s expansion and the risk of vaccine-resistant strains developing. In the context of COVID-19, the question of the feasibility and safety of vaccination for patients with primary immunodefi ciency and hereditary angioedema arises. The Russian Association of Allergists, Clinical Immunologists, and the National Association of Experts in Primary Immunodefi ciencies have developed and approved a position paper on the vaccination for patients with primary immunodefi ciency and hereditary angioedema against COVID-19. This position paper provides answers to key questions regarding vaccination for patients with these diseases. © 2020 Pharmarus Print Media License.

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.

The dynamics of inflammatory markers in COVID-19 patients treated with levilimab

Background: Levilimab (LVL) is a novel anti-IL6Rmonoclonal antibody against IL6Rα. Cytokine release syndrome plays the key role in the pathogenesis of a range of life-threatening conditions including the acute respiratory distress syndrome in severely ill COVID-19 patients. Thus, the use of LVL could be considered as anti-cytokine therapy with a potency to prevent the complications and progression of respiratory failure in COVID-19. Objectives: We analyzed the changes in the serum concentrations of inflammatory markers (Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IL-6) in patients treated with LVL or placebo as part of a phase III multicenter randomized double-blind placebo-controlled adaptive-design CORONA clinical study aimed to evaluate the efficacy and safety of LVL in subjects with severe COVID-19 (NCT04397562). Methods: A total of 217 patients were enrolled in the study, 206 patients were randomized, and 204 patients received the investigational product (IP, LVL or placebo). Study included men and non-pregnant women aged ≥18 years, hospitalized for severe COVID-19 pneumonia, receiving standard therapy according to the national guidelines. Patients with acute respiratory failure with the need in invasive respiratory support, septic shock, multiple organ failure or life expectancy less than 24 hours could not participate in the study. The use of other monoclonal antibodies and glucocorticoids for the treatment of COVID-19 were not allowed. Subjects were stratified according to the CRP level (CRP ≤ 7 mg/L;CRP ≥ 7 mg/L) and then randomized (1:1) into 2 groups to receive LVL 324 mg or placebo. LVL/ placebo were administered as a single subcutaneous injection, investigator and patients were unaware of the received therapy. Among secondary endpoints of the study changes from baseline in ESR, CRP and IL-6 concentrations were assessed. CRP level and ESR were measured before the IP administration and on Days 3, 5, 7, 14, 21, 29 and 30. Blood samples for the measurement of IL-6 concentration were obtained before the IP administration and then every day for 2 weeks after administration. Results: We observed the pronounced decrease of ESR in LVL group compared to Placebo group. The difference was statistically significant on Days 3 and 7: the median ESR change from baseline was -3 mm/h and +3 mm/h on Day 3, -11 mm/h and -3.1 mm/h on Day 7, in LVL and Placebo groups, respectively (p=0.0319 and p=0.0110, Days 3 and 7). The statistically significant difference in the change of CRP level was detected between the groups on Day 3: -26.6±41.9 mg/L and -19.2±58.2 mg/L in LVL and Placebo groups, respectively (p=0.0241). Numerically the same dynamics of ESR and CRP was observed over entire study period. The dynamics of IL-6 serum concentrations in LVL and Placebo groups was strikingly different. After LVL administration we detected the rapid significant increase in IL-6 concentration due to IL-6 receptors inhibition. Maximum change from baseline was observed on Day 3 (+91.9±117.7 pg/mL), on Day 14 the value was +31.9±62.7 pg/mL. In the Placebo group, the IL-6 concentration increased slightly until Day 4 (+5,1±76,5 pg/mL), and then decreased significantly (-39.2±55.1 pg/mL on Day 14) due to clinical improvement in this group. Conclusion: The significant differences in the dynamics of ESR, CRP and IL-6 after LVL administration compared to placebo confirmed the pharmacodynamic effect and its potency to prevent the excessive release of inflammatory substances in severely ill COVID-19 patients.

COVID-19 infection in patients with primary immunodeficiencies

The article presents data on the features of COVID-19 infection in patients with primary immunodeficiencies (PIDs) in the Russian Federation, obtained through the National association of experts in PID (NAEPID) registry. Materials and methods: from March 1, 2020 to October 15, 2020, 15 cases of close intrafamilial contact between PIDs patients and COVID-19 patients without reliable infection of the first and 23 cases of COVID-19 infection in PIDs patients were reported. Results: 6/23 infected people had asymptomatic course of infection, 9/23 patients - mild form, 8/23 -moderate form of disease, one patient had a severe course with a fatal outcome. 19/23 patients were under 18 years of age, which corresponds with the age data of the national Russia PID registry. Conclusion: perhaps this age composition partially explains the milder course of COVID-19 in PIDs patients compared to the European data. Other possible reasons for a milder course may be the lower pathogenicity of the coronavirus strain circulating in the Russian Federation. В статье представлены данные об особенностях течения COVID-19 у пациентов с первичными иммунодефицитами (ПИД) в РФ, собранные с помощью регистра Национальной ассоциации экспертов в области ПИД (НАЭПИД). Материалы и методы исследования: всего с 1 марта 2020 г. по 15 октября 2020 г. было репортировано 15 случаев тесного внутрисемейного контакта между пациентами с ПИД и больными COVID-19 без достоверного инфицирования первых и 23 случая инфицирования COVID-19 у пациентов с ПИД. Результаты: 6/23 инфицированных перенесли инфекцию бессимптомно, 9/23 - в легкой, 8/23 - в среднетяжелой форме, у одного пациента - тяжелое течение с летальным исходом. 19/23 пациентов были младше 18 лет, что коррелирует с данными национального регистра ПИД в РФ. Заключение: возможно, такое возрастное распределение частично объясняет более легкое течение COVID-19 у пациентов с ПИД по сравнению с европейскими данными. Другими возможными причинами, обусловливающими более легкое течение, могут быть меньшая патогенность штамма коронавируса, циркулирующего на территории РФ.

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.

Statement on management of children with allergic diseases during new coronaviral infection SARS-CoV-2 pandemic (COVID-19 infection)

The COVID-19 infection caused by the new coronavirus SARS-CoV-2 has become the real pandemic. Children account for 1-6% of all diagnosed COVID-19 cases. Generally, children have mild disease in comparison to adults, and their mortality rates are extremely low. Despite the fact that all the main efforts of the medical and political community are now focused on preventing the pandemic spread and organizing medical care for patients with moderate and severe COVID-19 course, we still have to remember to implement adequate help for patients with chronic diseases, especially for children with allergic diseases. The pandemic period coincided with natural weather period of dusting of causative plants, that led to annual escalation of both allergic rhinitis and asthma in patient group with specific sensitization to tree pollen. Leading experts of allergology (adapting to modern conditions) have created key guidelines on management of children with allergic diseases during the COVID-19 pandemic. These guidelines are based on the data and results from the Union of Pediatricians of Russia, Russian Association of Allergologists and Clinical Immunologists, European Academy of Allergy and Clinical Immunology (EAACI), European Respiratory Society (ERS), American Thoracic Society (ATS), Global Strategy for Asthma Management (GINA), Initiative on Allergic Rhinitis and its Impact on Asthma (ARIA/MACVIA).