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.

Nirmatrelvir/ritonavir for patients with SARS-CoV-2 infection and impaired kidney function during the Omicron surge.

Background: Nirmatrelvir/ritonavir has demonstrated effectiveness in high-risk patients with coronavirus disease 2019 (COVID-19). However, investigations on the efficacy and safety of nirmatrelvir/ritonavir in patients with kidney dysfunction are limited. Methods: Data were collected from the patients admitted to a COVID-19 referral center in Shanghai, China. Patients were at least 18 years of age and had a baseline estimated glomerular filtration rate (eGFR) of <60 ml/min/1·73 m2. The primary endpoint was a composite of all-cause mortality, intensive care unit admission, or cardiovascular events. The secondary endpoint was viral shedding. Results: Among the 195 participants, 73 received nirmatrelvir/ritonavir. A lower risk of the primary endpoint was observed in nirmatrelvir/ritonavir recipients compared with non-recipients [adjusted HR 0.56 (95% CI: 0.32-0.96); p = 0.035]. Nirmatrelvir/ritonavir recipients experienced a shorter duration of viral shedding [adjusted HR 3·70 (95%CI: 2.60-5.28); p < 0.001) and faster viral load clearance versus non-recipients. Among the nirmatrelvir/ritonavir users, earlier initiation of nirmatrelvir/ritonavir within 5 days since COVID-19 diagnosis was related with shorter viral shedding time (adjusted HR 7.84 [95% CI: 3.28-18.76]; p < 0.001) compared to late initiation. No patients reported serious adverse events during treatment. Conclusion: Our findings support the early initiation of nirmatrelvir/ritonavir for high-risk patients with impaired kidney function. This could improve patient outcomes and shorten the viral shedding period.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.

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.