The use of neutralizing monoclonal antibodies against SARS-CoV-2 in hemodialysis patients

Patients with end-stage kidney disease undergoing hemodialysis have one of the highest COVID-19 mortality rates. The use of innovative methods capable of optimizing their treatment outcomes is important for clinical practice. Aims - to investigate the efficacy and safety of neutralizing monoclonal antibodies in COVID-19 patients treated with hemodialysis. Material and methods. We conducted a retrospective controlled single-center study with 102 COVID-19 patients on maintenance hemodialysis involved (M: 67;65.7%;W: 35;34.3%), aged 57.2+/-15.3 years. PCR-detected SARS-CoV-2 infection was diagnosed in all patients. Neutralizing monoclonal antibodies were administered to 69 patients, who formed the study group (group 1). The control group included 33 patients (group 2). The combination of bamlanevimab and etesevimab was the most frequent therapy used (in 59 patients). Results. In the course of the disease, group 1 patients, compared to those of group 2, had statistically significantly higher blood oxygen saturation values (94.2+/-5.7 vs 89.8+/-10.7);they required less frequent oxygen support (29.0 vs 54.5%) and ICU treatment (18.8 vs 48.5%), respectively. Fatal outcomes occurred in 4 (5.8%) of 69 patients who received neutralizing antibodies and in 6 (18.2%) of 33 patients who did not receive the therapy, p<0.05. Except for one patient, all other patients in both groups developed an unfavorable outcome due to progressive lung damage. However, only 4 of 6 (2/3) patients with progressive lung damage died in group 1, whereas the similar course of the disease proved fatal in all cases in group 2. Conclusion. The use of neutralizing monoclonal antibodies in hemodialysis patients is safe and effective when the drugs are administered early, the pulmonary process progression is insignificant and dominant SARSCoV-2 variants are sensitive to them.Copyright © 2022 Tomsk Polytechnic University, Publishing House. 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.

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.