Resolution Consensus Statement Neutralizing monoclonal antibodies for treatment of COVID-19 - a role in the treatment of vulnerable categories of patients.

In December 2022, the Council of Experts was held. It purpose was to determine the place of virus-neutralizing monoclonal antibodies (NMA) in the ethiotropic treatment of COVID-19 in vulnerable categories of patients. The main issues were identified and their solutions were proposed. At the first visit of pregnant women due to COVID-19, proactive identification of risk factors and early prescription of NMA are recommended, preferably - with published safety data in this category of patients (casirivimab + imdevimab). In patients with oncological and other chronic (rheumatology, pulmonology, gastroenterology) diseases, prophylactic use of NMA is recommended. regardless of the severity of the disease. For patients with chronic pathology regardless of the severity of the disease an early prescription of ethiotropic therapy must be provided, combating the long-term circulation of the virus. To solve the problem of late treatment prescription, it is necessary to: use rapid tests, prescribe NMA if indicated, even if the patient presents late, introduce digital technologies to transfer information about COVID-19 cases between healthcare institutions (HI), create call centers for primary triage of patients, daily hospitals to reduce the burden on the HI. The issue of NMA using related to changes in their activity against new variants of SARS-CoV-2 remains relevant. Among the proposed solutions are: priority of indications over information about the activity of NMA, the diversification of the choice of NMA in HI, taking into account clinical experience, indications for use and prognosis of NMA activity, the use of combined forms of NMA (for example, casirivimab + imdevimab) or a combination of NMA with other means of ethiotropic therapy.Copyright © 2023, Dynasty Publishing House. All rights reserved.

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.

Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program.

Objectives. To study the prevalence and clinical manifestations of postcovid syndrome (PCS) in out-patients and to assess the efficacy of treatment with the drug Cortexin at doses of 10 and 20 mg i.m. for 10 days. Materials and methods. A total of 979 patients with PCS from regions of the Russian Federation, Azerbaijan, Kyrgyzstan, and Kazakhstan were studied; mean age was 54.6 ± 4.5 years; duration of COVID-19 was from one month upwards. Investigations involved three visits. The first was on the day of consultation (assessment of complaints, analysis of scale indicators, prescription of drug Cortexin at a dose of 10 or 20 mg i.m. for 10 days). The second visit (telephone consultation) was on day 10-14. The third visit was on day 30 of out-patient treatment. Assessment of patients' status used an asthenia assessment scale (MFI-20), a brief mental state assessment scale (MMSE), the Schulte test, and the Subjective Treatment Quality Assessment Scale. Results. The proportion of patients with PCS was up to 30% of all neurological admissions. The commonest manifestations were: fatigue, general weakness, decreased memory and concentration of attention, vertigo, sleep impairment, irritability, and aggression; less frequent were breathlessness, pain, increased sweating, anosmia, hyposmia, dysgeusia, paresthesia, hair loss, degradation of vision, tachycardia, allergic reactions, menstrual cycle impairments, erectile dysfunction, panic attacks, suicidal ideation, depression and refusal to eat meat. Conclusions: No associations were found between clinical symptomatology and the severity of COVID-19, the volume of lung tissue affected, or different periods of postcovid syndrome. Cortexin was found to be effective at doses of 10 and 20 mg for correcting the cognitive and asthenic manifestations of PCS. Cortexin was found to have anti-anxiety, antidepressant, and anxiolytic effects, which were more marked at the 20-mg dose.

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.

Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program

Objectives. To study the prevalence and clinical manifestations of postcovid syndrome (PCS) in out-patients and to assess the efficacy of treatment with the drug Cortexin at doses of 10 and 20 mg i.m. for 10 days. Materials and methods. A total of 979 patients with PCS from regions of the Russian Federation, Azerbaijan, Kyrgyzstan, and Kazakhstan were studied;mean age was 54.6 ± 4.5 years;duration of COVID-19 was from one month upwards. Investigations involved three visits. The first was on the day of consultation (assessment of complaints, analysis of scale indicators, prescription of drug Cortexin at a dose of 10 or 20 mg i.m. for 10 days). The second visit (telephone consultation) was on day 10–14. The third visit was on day 30 of out-patient treatment. Assessment of patients’ status used an asthenia assessment scale (MFI-20), a brief mental state assessment scale (MMSE), the Schulte test, and the Subjective Treatment Quality Assessment Scale. Results. The proportion of patients with PCS was up to 30% of all neurological admissions. The commonest manifestations were: fatigue, general weakness, decreased memory and concentration of attention, vertigo, sleep impairment, irritability, and aggression;less frequent were breathlessness, pain, increased sweating, anosmia, hyposmia, dysgeusia, paresthesia, hair loss, degradation of vision, tachycardia, allergic reactions, menstrual cycle impairments, erectile dysfunction, panic attacks, suicidal ideation, depression and refusal to eat meat. Conclusions: No associations were found between clinical symptomatology and the severity of COVID-19, the volume of lung tissue affected, or different periods of postcovid syndrome. Cortexin was found to be effective at doses of 10 and 20 mg for correcting the cognitive and asthenic manifestations of PCS. Cortexin was found to have anti-anxiety, antidepressant, and anxiolytic effects, which were more marked at the 20-mg dose.

[Determination of the prevalence of postcovid syndrome and assessment of the effectiveness of the drug Cortexin in the treatment of neurological disorders in patients with postcovid syndrome. Results of the multicenter clinical and epidemiological observational program CORTEX]. / Opredelenie rasprostranennosti postkovidnogo sindroma i otsenka effektivnosti preparata Korteksin v terapii nevrologicheskikh narushenii u patsientov s postkovidnym sindromom. Rezul'taty mnogotsentrovoi nablyudatel'noi programmy KORTEKS.

OBJECTIVE: To study the prevalence of clinical manifestations of postcoid syndrome in patients at an outpatient neurological appointment, to evaluate the effectiveness of therapy regimens using Cortexin at doses of 10 mg and 20 mg IM for 10 days. MATERIALS AND METHODS: 674 neurologists from all regions of the Russian Federation, Azerbaijan, Kyrgyzstan and Kazakhstan took part in the study. A total of 979 COVID-19 patients were recruited. The average age is 54.6±0.45 years. The duration of the transferred SARS-CoV-2 days and from 1 month or more 12. 3 visits were carried out: 1 on the day of treatment (assessment of complaints, analysis of scale indicators, prescription of the drug Cortexin in doses of 10-20 mg/m for 10 days). 2 (telephone survey) visit for 10-14 days, 3 visit - for 30 days at the reception. The condition was assessed using the Asthenia Assessment Scale (MFI-20), the Brief Mental Status Assessment Scale (MMSE questionnaire), the Schulte test, and the Subjective Treatment Quality Assessment Scale. RESULTS: The daily proportion of patients with complaints after a previous coronavirus infection was 30% in the total structure of neurological admission. The most common complaints: fatigue, general weakness, decreased memory and concentration, dizziness, sleep disturbance, irritability, aggression, shortness of breath, pain syndromes, excessive sweating, anosmia, hyposmia, perverted taste of paresthesia, hair loss, blurred vision, unstable blood pressure, tachycardia, allergic reactions, menstrual irregularities, erectile dysfunction, apathy, panic attacks, suicidal thoughts, depression, refusal to eat meat. CONCLUSION: There was no significant correlation of clinical symptoms with the severity of COVID-19, the percentage of lung tissue damage, and different periods of postcovid syndrome. The clinical efficacy of the drug Cortexin in dosages of 10 and 20 mg for the correction of cognitive and asthenic disorders has been proven. Revealed anti-anxiety, antidepressant and anxiolytic activity of Cortexin is more pronounced when using a dosage of 20 mg.

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.

Eculizumab in treatment of ANCA-associated vasculitis complicated with Covid-19 Clinical observations

Vasculitis associated with the antineutrophilic cytoplasmic antibodies (ANCA) is an autoimmune systemic severe, often life-threatening, disease characterized by necrotizing infl ammation of small vessels. In 75-90% of cases of ANCA-associated vasculitis (AAV), a rapidly progressive pauci-immune necrotizing crescentic glomerulonephritis develops. Despite current treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk during the fi rst year of disease compared with healthy subjects. This high mortality is attributed mainly to infections and vasculitis activity. Recent data suggest that the activation of the complement system, and in particular the alternative complement pathway, plays a signifi cant role in the pathogenesis of AAV. It has been suggested that neutrophils primed by infection or pro-infl ammatory cytokines release properdin, which activates an alternative complement cascade with cleavage of C5 into C5a and C5b. Anaphylatoxin C5a binds to receptors on the surface of neutrophils, enhancing their priming and activation and thus contributing to the infl ammation. The randomized clinical trial showed that the selective C5a-receptor inhibitor avakopan was effective in the treatment of AAV. However, avacopan is currently not available in the everyday clinical practice. On the other hand, reports showing successful usage of monoclonal antibody against C5 eculizumab in severe AAV had been published. Here we present four cases of AAV complicated by COVID-19, for which conventional therapy with cy?lophosphamide could not be applied due to the particularly high risk of serious infectious complications, and eculizumab was used off-label by decision of the medical council and special commission. Taking this decision, we took into account data demonstrating the role of complement activation and, in particular, C5a in the pathogenesis of acute lung disease, induced by pathogenic viruses. Moreover, the successful usage of eculizumab in severe COVID-19 was reported recently. Thus, we sought to apply an approach aimed simultaneously at the pathogenetic mechanisms of both AAV and viral lung damage. © 2020 JSC Vidal Rus. All rights reserved.