EXPERIENCE IN THE USE OF NEUTRALIZING MONOCLONAL ANTIBODIES IN KIDNEY TRANSPLANT RECIPIENTS WITH COVID-19.

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective(s): to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.Copyright © 2023 Russian Transplant Society. All rights reserved.

Experience in the use of neutralizing monoclonal antibo dies in kidney transp lant recipients withC OVID -19

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective: to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by.aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.

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.

SARS-CoV-2 infection in kidney transplant recipients

The study aimed to assess the clinical course and risk factors for adverse outcomes, as well as the treatment options for COVID-19 in renal transplant recipient (RTR). Patients and methods: a retrospective study included 279 RTRs (M 60.9%, age 49.9±10.9 years), infected with SARS-CoV-2 from 01.04.2020 to 30.11.2020. After confirmation of COVID-19 by PCR and chest CT, MMF/Aza were canceled. In severe cases, the CNI dose was minimized while that of CS was increased. Observation endpoints: hospital discharge/recovery or death. Results: SARS-CoV-2 was identified in 84.2% of RTRs. In almost 90% of patients, the COVID-19 was confirmed by CT data. Duration after transplantation at the time of infection was 54.0 (14.0;108.0) months, in 17.6% of cases it was 6 months or less. 223/79.9% RTRs were treated in the hospital. The period from the onset of the disease to the hospitalization was 6.8±4.5 days. Severe lung damage (>50%) occurred in 43.1% RTRs;45.3% of patients required respiratory support. Hospital mortality was 13.9%, overall mortality was 11.1%. The most common cause of death (93.5%) was acute respiratory distress syndrome (ARDS). The risk factors associated with an unfavorable outcome were a high comorbidity index, the severity of the pulmonary lesion, the degree of graft dysfunction at the onset of the disease, decreased SpO2 and the use of mechanical ventilation, as well as anemia, leukocytosis, lymphocytopenia, and hypoalbuminemia, increased levels of creatinine, AST, CRP, LDH, and D-dimer, interleukin-6 and procalcitonin. Scr during the course of the disease increased from 171.6±78.0 μM to 221.5±121.3 μM (p<0.01) with no signs of acute rejection. In 2 recipients with severe graft failure at the time of infection with SARS-CoV-2, HD was resumed from the moment of hospitalization. We were unable to identify the effect of hydroxychloroquine on the outcome of COVID-19. At the same time, mortality in patients with hydroxychloroquine use was higher than in recipients treated with immunobiological drugs: 25.6% and 11.4%, respectively, p<0.02. When immunomodulators were combined with dexamethasone, mortality decreased to 4.8%. The independent factors of adverse outcome were high levels of procalcitonin (p<0.019) and mechanical ventilation (p<0.001). Conclusion: COVID-19 in RTRs is characterized by a severe course and high mortality, which necessitates hospitalization of the majority of infected patients. An increase in procalcitonin levels and the need for mechanical ventilation were independent predictors of an unfavorable outcome of COVID-19. © 2021 JSC Vidal Rus. All rights reserved.

COVID-19 in solid organ transplant recipients: initial report from national multicenter observational study "ROKKOR-recipieni"

We herein present our initial report from «ROKKOR-recipient», a national multicenter observational study. The prevalence, risk factors, clinical manifestations and outcomes ofthe novel coronavirus disease 2019 (COVID-19) in solid organ transplant recipients receiving immunosuppressive therapy were investigated. The study enrolled 251 COVID-19 patients (220 kidney recipients, 7 liver recipients, 1 liver-kidney recipient, and 23 heart recipients). The subjects came from 20 regions in Russia. The symptoms, clinical presentation, imaging and lab test results, therapy and outcomes of COVID-19 were described. It was established that solid organ transplant recipients with COVID-19 have a higher risk of developing adverse events. Predictors of adverse events include associated cardiovascular diseases, pulmonary diseases, diabetes, and kidney failure. Symptoms of the disease include dyspnea, rash and catarrhal signs, as well as initial low blood oxygen saturation (SpO₂ <92%), leukocytosis (white blood cell count >10 х 10⁹/L), elevated creatinine levels (>130 mumol/L) and a marked decrease in glomerular filtration rate, requiring hemodialysis. Performing organ transplant surgery in COVID-19 does not increase the risk of adverse events but could save the lives of waitlisted terminally ill patients. В статье представлены первые результаты национального многоцентрового исследования «РОККОР-реципиент», имевшего целью изучить распространенность, факторы риска, клинические проявления и исходы новой коронавирусной инфекции (COVID-19) у реципиентов солидных органов, получающих иммуносупрессивную терапию. В исследование включен 251 пациент (220 реципиентов почки, 7 реципиентов печени, 1 реципиент печени и почки, 23 реципиента сердца) из 20 регионов России c COVID-19. Описаны симптомы, клинические проявления, результаты инструментальных и лабораторных обследований, терапия и исходы коронавирусной инфекции. Выявлено, что наличие трансплантированного органа повышает риск нежелательных событий на фоне COVID-19, предикторами которых являются сопутствующие сердечно-сосудистые, легочные заболевания, сахарный диабет и почечная недостаточность, наличие в качестве симптомов манифестации заболевания одышки, сыпи и катаральных явлений, а также исходно низкая сатурация кислорода (SpO₂ <92%), лейкоцитоз более 10 х 10⁹/л, повышение уровней креатинина более 130 мкмоль/л и значимое снижение скорости клубочковой фильтрации, требующее проведения гемодиализа. Выполнение трансплантации органов на фоне пандемии COVID-19 не повышает риск развития нежелательных событий у реципиентов, но позволяет спасти жизни больных с терминальными заболеваниями, включенных в лист ожидания.