Monoclonal antibodies to the interleukin-6 receptor in the treatment of COVID-19 in patients with chronic kidney disease

Interleukin-6 (IL-6) plays a key role in the pathogenesis of COVID-19, which determines the indications for the therapeutic use of its antagonists. However, data on their effectiveness and optimal timing of appointment are contradictory. The question of the possibility of their use in patients with impaired kidney function has not been studied. The aim of the study is to evaluate the efficacy and safety of the use of monoclonal antibodies to IL-6 receptors in COVID-19 in patients with chronic kidney disease (CKD) of stages 2-5 (predialysis) who do not need renal replacement therapy. Material and methods. A clinical retrospective uncontrolled single-center study included 45 patients (60% of men) with CKD stages 2-5 aged 22-95 years (median - 58 years) hospitalized with predominantly severe uncritical COVID-19 infection. Treatment of COVID-19 was carried out in accordance with the Interim guidelines for the prevention and treatment of new coronavirus infection of the Ministry of Health of Russian Federation. Results. The majority of patients (n=36;73.3%) had CKD stage 3b-5, CKD stage 2 was in 7 (15.5%) and stage 3a - in 5 (11.1%) patients. The median serum creatinine level (Cr) was 164 [131;292] mumol/l, glomerular filtration rate (GFR) was 30 [13;49] ml/min/1.73 m2, CRP 67.5 [37.2;106.75] mg/l. The introduction of monoclonal antibody to IL-6 receptors led to a decrease in the activity of the infectious process (CRP 1.55 [0.33;4.15] mg/l, p<0.001), regression of pneumonia, which did not require mechanical ventilation and hospitalization in the intensive care unit. According to the decision of the medical commission, patients were injected with monoclonal antibodies to IL-6 receptors: tocilizumab (n=36;80%), levilimab (n=2;4.4%), combined therapy with two drugs (n=7;15.5%). Therapy with IL-6 antagonists did not have a negative effect on kidney function. The levels of Cr decreased on average from 224.3+/-145.2 mmol/l at admission to 160+/-92.55 mmol/l at discharge (p<0.001), GFR increased from 32.6+/-20.9 ml/min/1.73 m2 at admission to 53+/-31.7 ml/min/1.73 m2 at discharge (p<0.001). In the majority of patients (n=36, 80%) GFR has risen, and only in 9 (20%) cases it remained approximately at the same low level. No serious adverse events have been reported with the use of IL-6 antagonists, as well as concomitant infectious complications. No deaths have been reported. The median length of stay in bed was 14 [10;19] days. Conclusion. The results of the study allow us to state that in patients with CKD, monoclonal antibodies to IL-6 receptors have a good safety profile and can be successfully used in moderate and severe forms of COVID-19, regardless of the state of kidney function.Copyright © 2022 by the authors.

COVID-19 in hemodialysis patients

Objective. Evaluation of clinical observation, the course, the risk factors, and treatment options for SARS-CoV-2 infection in hemodialysis patients with end-stage chronic kidney disease. Material and methods. The retrospective, single-center, uncontrolled study involved 231 patients (132 M/99 W) aged 61.7+/-14.7 years with COVID-19 diagnosed. The SPSS software package was used for statistical analysis. Results. 72 (31.2%) of patients died, 68 (94.4%) of them had ARDS as the main cause of death. Comparative analysis in groups with favorable and unfavorable outcomes of the disease showed that age (68.1+/- 13.2 years vs 58.7+/-14.5 years, p<0.0001) and the comorbidity index (8.8+/-2.2 vs 6.2+/-2.6, p<0.0001) were significantly higher in those who have died compared to survivors. According to CT data, they were more likely to have 3rd or 4th-degree lung damage (72.2 vs 36.5%, p<0.0001), and the minimum oxygen saturation index: 67.6+/-12.8 and 87.8+/-10.9%, respectively (p<0.0001). Somorbidity index and the need for invasive ventilation were independent predictors of the fatal outcome of COVID-19. Early administration of monoclonal antibodies to IL-6 (in the first 3 days after hospitalization) in patients with a low prevalence of the pulmonary process (CT stage 1-2) was associated with a significantly lower frequency of fatal outcome. Conclusions. SARS-CoV-2 infection in HD patients is characterized by a high rate of mortality. Predictors of severe disease in this population are comorbidity index and the need for invasive ventilation.Copyright © Infectious Diseases: News, Opinions, Training.

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.

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. © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

The use of therapeutic plasma exchange in the severe forms of COVID-19 in patients with renal fаilure

Cytokine release syndrome plays a key role in the pathogenesis of COVID-19. Therapeutic plasma exchange (TPE) by removing pathogenic cytokines, can favorably influence the course of severe forms of this disease. However, conclusive studies on this issue are still lacking. Only descriptions of individual clinical cases or small cohort studies have been published. There are no data on the use of TPE in patients with renal failure in the literature. The study aims to evaluate the effect of TPE in the severe forms of COVID-19 in patients with advanced renal failure. Material and Methods: a retrospective, uncontrolled, observational study enrolled 211 patients aged 60,4±13,2. 90.5% of them received renal replacement therapy: 66.8% – hemodialysis, 9.5% – peritoneal dialysis, 14.2% renal transplant recipients with moderate to severe dysfunction, and 9.5% had acute kidney injury on chronic kidney disease that did not require dialysis treatment. Results. All patients were divided into 2 groups: 124 (58.8%) patients (treated from 01.07. to 15.12.2020), who received TPE (TPE group), and 87 (41.2%) patients (observed from 01.04. to 30.06.2020), who did not treat with TPE (control group). The condition of patients in both groups at admission was approximately comparable. The clinical picture of the disease was dominated by severe pneumonia. There were no significant differences in inflammatory markers: both groups had no significant differences in levels of CRP, ferritin, lactate dehydrogenase, or D-dimer. The groups also did not differ significantly in lymphopenia, thrombocytopenia, and azotemia. The mortality rate in the group of patients who did not receive TPE was 73.5%, while in the TPE group it was 45.16% (p<0.001). Among patients on chronic dialysis, the mortality rate in the control subgroup was 74.6%, and in the TPE subgroup – 44.15% (p<0.001). Conclusion:therapeutic plasma exchange is an efficient approach to the treatment of severe forms of COVID-19 in patients with advanced renal failure. Its effect, however, may be limited by the risk of death due to uremia. © 2022 JSC Vidal Rus. All rights reserved.

Monoclonal antibodies to the interleukin-6 receptor in the treatment of COVID-19 in patients with chronic kidney disease

Interleukin-6 (IL-6) plays a key role in the pathogenesis of COVID-19, which determines the indications for the therapeutic use of its antagonists. However, data on their effectiveness and optimal timing of appointment are contradictory. The question of the possibility of their use in patients with impaired kidney function has not been studied. The aim of the study is to evaluate the efficacy and safety of the use of monoclonal antibodies to IL-6 receptors in COVID-19 in patients with chronic kidney disease (CKD) of stages 2-5 (predialysis) who do not need renal replacement therapy. Material and methods. A clinical retrospective uncontrolled single-center study included 45 patients (60% of men) with CKD stages 2-5 aged 22-95 years (median - 58 years) hospitalized with predominantly severe uncritical COVID-19 infection. Treatment of COVID-19 was carried out in accordance with the Interim guidelines for the prevention and treatment of new coronavirus infection of the Ministry of Health of Russian Federation. Results. The majority of patients (n=36;73.3%) had CKD stage 3b-5, CKD stage 2 was in 7 (15.5%) and stage 3a - in 5 (11.1%) patients. The median serum creatinine level (Cr) was 164 [131;292] μmol/l, glomerular filtration rate (GFR) was 30 [13;49] ml/min/1.73 m2, CRP 67.5 [37.2;106.75] mg/l. The introduction of monoclonal antibody to IL-6 receptors led to a decrease in the activity of the infectious process (CRP 1.55 [0.33;4.15] mg/l, p<0.001), regression of pneumonia, which did not require mechanical ventilation and hospitalization in the intensive care unit. According to the decision of the medical commission, patients were injected with monoclonal antibodies to IL-6 receptors: tocilizumab (n=36;80%), levilimab (n=2;4.4%), combined therapy with two drugs (n=7;15.5%). Therapy with IL-6 antagonists did not have a negative effect on kidney function. The levels of Cr decreased on average from 224.3±145.2 mmol/l at admission to 160±92.55 mmol/l at discharge (p<0.001), GFR increased from 32.6±20.9 ml/min/1.73 m2 at admission to 53±31.7 ml/min/1.73 m2 at discharge (p<0.001). In the majority of patients (n=36, 80%) GFR has risen, and only in 9 (20%) cases it remained approximately at the same low level. No serious adverse events have been reported with the use of IL-6 antagonists, as well as concomitant infectious complications. No deaths have been reported. The median length of stay in bed was 14 [10;19] days. Conclusion. The results of the study allow us to state that in patients with CKD, monoclonal antibodies to IL-6 receptors have a good safety profile and can be successfully used in moderate and severe forms of COVID-19, regardless of the state of kidney function. © 2022 by the authors.

[COVID-19 in haemodialysis patients: result analysis of the first year of the pandemic].

BACKGROUND: Present concepts of the novel coronavirus infection prognosis in haemodialysis (HD) patients are rather controversial. There is little information on therapy efficiency and safety in such patients. We studied COVID-19 course specifics, prognostic factors associated with fatal outcomes, therapy efficiency and its transformation at different stages of the pandemic first year. MATERIALS AND METHODS: Single-centre retrospective uncontrolled study included 653 COVID-19 HD-patients treated at Moscow City Nephrology Centre from April 1 to December 31, 2020. RESULTS: This period mortality rate was 21.0%. Independent predictors of COVID-19 unfavourable outcome in HD patients were pulmonary lesion extension (CT grades 34), high comorbidity index, and mechanical ventilation. Approaches to COVID-19 treatment modified significantly at different periods. Immunomodulatory drugs (monoclonal antibodies to IL-6, corticosteroids) were used largely at later stages. With tocilizumab administration, mortality was 15.1%, tocilizumab together with dexamethasone 13.3%; without them 37.8% (р0,001). Tocilizumab administration in the first 3 days after hospitalization of patients with CT grades 12 was associated with more favourable outcomes: 1 out of 29 died vs 6 out of 20 (tocilizumab administered at later periods); p0.04. There was no significant difference in death frequency in patients with CT grades 34 depending on tocilizumab administration time. CONCLUSION: COVID-19 in HD patients can manifest in a severe course with unfavourable outcome. It is urgent to identify reliable disease outcome predictors and develop efficient treatment in this population.

Novel coronavirus infection and hemodialysis: course and predictors of unfavorable outcome

In the context of the COVID-19 pandemic, patients with end-stage CKD receiving hemodialysis replacement therapy (HD) were at risk of SARS-CoV-2 infection due to the specifics of treatment and the immunodeficiency state caused by uremia. The aim of the study was to analyze the characteristics of the course, prognostically unfavorable factors, and outcome of COVID-19 in HD patients of the second wave of the pandemic. Materials and methods: a retrospective study was carried out on the material of observations of 325 HD patients infected with SARS-CoV-2 in the period from 09/01/2020 to 12/31/2020. The patients' age was 60.1±14.0 years. The duration of HD treatment was 30.0 (9.5;66.0) months. The endpoint was taken as the discharge from the hospital or death. Results: in 264 out of 325 (81.2%) patients, the diagnosis of COVID-19 was confirmed by the identification of SARS-CoV-2 RNA. CT scan of the chest showed signs of viral pneumonia in all patients. Mortality was 15.1% (49 out of 325 pts). In 79.7% of patients, the cause of death was ARDS. Comparative analysis showed that patients with a fatal outcome (group 2) were older (69.2±10.6 years) than patients with a successful course (group 1) of the disease (58.5±13.9 years), and differed in higher comorbidity index (7.8±1.9 versus 5.9±2.2, respectively). SpO2 in groups 2 and 1 was 65.2±10.1% and 92.1±6.4%, respectively (p<0.001). In the deceased patients, anemia, leukocytosis, thrombocytopenia, and hypoalbuminemia were significantly more pronounced, as well as indicators of GGT, alkaline phosphatase, ferritin, CRP, LDH, and D-dimer. In the fatal group, the proportion of patients with a procalcitonin level of more than 2 ng/ml was also higher. In multivariate analysis, only high comorbidity index and the need for mechanical ventilation were the independent predictors of the unfavorable outcome. In the group of patients with the favorable outcome, the combined therapy with immunobiological drugs and dexamethasone were used significantly more often than in the deceased group, while the frequency of their “isolated” use in the compared groups was comparable. Conclusions: COVID-19 in HD patients is characterized by severe course and high mortality. Independent predictors of an unfavorable outcome of the disease were a high comorbidity index and the need for invasive lung ventilation. Early use of immunobiological drugs and dexamethasone in combination with anticoagulants increases the effectiveness of treatment of severe forms of SARS-CoV-2 infection in HD patients. © 2021 JSC Vidal Rus. All rights reserved.

COVID-19 in hemodialysis patients

Objective. Evaluation of clinical observation, the course, the risk factors, and treatment options for SARS-CoV-2 infection in hemodialysis patients with end-stage chronic kidney disease. Material and methods. The retrospective, single-center, uncontrolled study involved 231 patients (132 M/99 W) aged 61.7±14.7 years with COVID-19 diagnosed. The SPSS software package was used for statistical analysis. Results. 72 (31.2%) of patients died, 68 (94.4%) of them had ARDS as the main cause of death. Comparative analysis in groups with favorable and unfavorable outcomes of the disease showed that age (68.1± 13.2 years vs 58.7±14.5 years, p<0.0001) and the comorbidity index (8.8±2.2 vs 6.2±2.6, p<0.0001) were significantly higher in those who have died compared to survivors. According to CT data, they were more likely to have 3rd or 4th-degree lung damage (72.2 vs 36.5%, p<0.0001), and the minimum oxygen saturation index: 67.6±12.8 and 87.8±10.9%, respectively (p<0.0001). Сomorbidity index and the need for invasive ventilation were independent predictors of the fatal outcome of COVID-19. Early administration of monoclonal antibodies to IL-6 (in the first 3 days after hospitalization) in patients with a low prevalence of the pulmonary process (CT stage 1-2) was associated with a significantly lower frequency of fatal outcome. Conclusions. SARS-CoV-2 infection in HD patients is characterized by a high rate of mortality. Predictors of severe disease in this population are comorbidity index and the need for invasive ventilation. © Infectious Diseases: News, Opinions, Training.