Sotrovimab in SARS-COV-2 chronic hemodialysis patients in the Omicron era. Is intradialytic administration feasible? Report of 4 cases.

Chronic hemodialysis patients are at high risk of morbidity and mortality in case of SARS-CoV-2 infection and they may need to be treated with monoclonal antibodies, either because they have not been vaccinated, or because they have a low anti spike antibody titer. Administration of Sotrovimab has recently been proposed for hemodialysis patients, but data are on the results lacking. We report on four cases of chronic dialysis patients who received Sotrovimab during intermittent dialysis sessions. In our series, no adverse reactions were recorded; intradialytic administration resulted safe and allowed an adequate observation time without prolonging hospital stay in chronic hemodialysis outpatients.

Anti-Inflammatory Approach in Chronic Dialysis Patients with SARS-CoV-2: ATA or PMMA Dialyzers?

INTRODUCTION: High-flux hemodialysis membranes may modulate the cytokine storm of SARS-CoV-2, but their impact on chronic hemodialysis (CHD) patients is unknown. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers and clinical outcomes in CHD patients with SARS-CoV-2. METHODS: A prospective, observational study on CHD patients with SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021. Pre- and postdialysis C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) were determined at each session. Patients who underwent on-line hemodiafiltration (OLHDF) with a PMMA dialyzer were compared with those treated with OLHDF with a ATA dialyzer. The primary endpoint was the differences in the reduction ratio per session (RR) of CRP, PCT, IL-6, and IL-6 RR >25%. RESULTS: We consecutively enrolled 74 CHD patients with COVID-19, 48 were treated with ATA membrane, and 26 with PMMA. Median IL-6 RR was higher in the ATA group compared to PMMA (17.08%, IQR -9.0 to 40.0 vs. 2.95%, IQR -34.63 to 27.32). Median CRP RR was 7.77% (IQR 2.47-13.77) in the ATA group versus 4.8% (IQR -2.65 to 11.38) in the PMMA group (p = 0.0017). Median PCT-RR% was 77.38% (IQR 70.92-82.97) in ATA group versus 54.59% (IQR 42.62-63.16) in the PMMA group (p < 0.0001). A multiple logistic regression analysis with IL-6 RR >25% as the outcome including the membrane employed, pre-dialysis IL-6, CRP, PCT, and ferritin showed that ATA led to a higher probability to reach the outcome (OR 1.891, 95% CI 1.273-2.840, p = 0.0018) while higher CRP favors the risk of lower IL-6 RR values (OR 0.910, 95% CI 0.868-0.949, p ≤ 0.0001). CONCLUSIONS: In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile, regarding IL-6 RR, compared to PMMA.

Interleukin-6 and Outcome of Chronic Hemodialysis Patients with SARS-CoV-2 Pneumonia.

Background and Objectives: Chronic hemodialysis (CHD) patients are at increased risk of SARS-CoV-2 infection and the related complications and mortality of COVID-19 due to the high rate of comorbidities combined with advanced age. This observational study investigated the clinical manifestations of SARS-CoV-2 infection in CHD and the risk factors for patients' death. Materials and Methods: The study included 26 CHD patients with SARS-CoV-2 pneumonia detected by positive RT-PCR on nasopharyngeal swabs and high-resolution computed tomography at hospital admission, aged 71 + 5.9 years, 14 of which (53.8%) were male, 20 (77%) under hemodiafiltration, and 6 (23%) on standard hemodialysis, with a median follow-up of 30 days. Results: Simple logistic regression analysis revealed that the factors associated with a higher risk of death were older age (OR: 1.133; 95%CI: 1.028-1.326, p = 0.0057), IL-6 levels at admission (OR: 1.014; 95%CI: 1.004-1.028, p = 0.0053), and C-reactive protein (OR: 1.424; 95%CI: 1.158-2.044, p < 0.0001). In the multiple logistic regression model, circulating IL-6 values at admission remained the only significant prognosticator of death. The ROC curve indicated the discriminatory cut-off value of 38.20 pg/mL of blood IL-6 for predicting death in chronic hemodialysis patients with SARS-CoV-2 pneumonia (sensitivity: 100%; specificity: 78%; AUC: 0.8750; p = 0.0027). Conclusions: This study identified a threshold of IL-6 levels at hospital admission for death risk in CHD patients with SARS-CoV-2 pneumonia. This might represent a valuable outcome predictor, feasibly better than other clinical, radiological, or laboratory parameters and preceding the IL-6 peak, which is unpredictable.

Anti-Inflammatory Approach in Chronic Dialysis Patients with SARS-CoV-2: ATA or PMMA Dialyzers?

BACKGROUND AND AIMS High flux haemodialysis membranes may modulate the cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their impact in chronic haemodialysis (CHD) patients is not assessed [1, 2]. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers in CHD patients with SARS-CoV-2. METHOD A prospective, observational study on CHD patients (age ≥18 years) affected by SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021 and dialysis was performed at S. Orsola University Hospital (Bologna, Italy) Dialysis Unit. Mechanical ventilation at diagnosis was exclusion criteria. Pre- and post-dialysis C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were determined at each session and corrected for haemoconcentration during the complete SARS-CoV-2 period. Patients who underwent online haemodiafiltration (OLHDF) with PMMA dialyzer (Filtryzer BG-U™, Toray, surface area 2.1 m2 cut-off 20 kDa, KUF 43 mL/h/mmHg) were compared with those who underwent OLHDF with ATA dialyzer (SolaceaTM Nipro, surface area 2.1 m2 cut-off 45 kDa, KUF 72 mL/h/mmHg). The primary endpoint was to assess the differences in the reduction ratio/session (RR) of CRP, PCT and IL-6. RESULTS A total of 74 patients were enrolled, 48 were treated with ATA and 26 were with PMMA (420 versus 191 dialysis sessions). The main results are shown in Table 1. Median IL-6RR% was higher for ATA [17.08%, interquartile range (IQR) −9.0 to 40.0 versus 2.95%, IQR −34.63 to 27.32]. CRP and PCT showed higher RR with ATA in comparison to PMMA. When IL-6RR > 25% was the dependent variable in the multiple logistic regression analysis only ATA showed a significant correlation [odds ratio (OR) 1.891, 95% confidence interval (95% CI) 1.273–2.840, P = .0018) while higher CRP favoured the risk of lower IL6RR (OR 0.9101, 95% CI 0.868–0.949, P < 0.0001) (Table 2). CONCLUSION In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile than PMMA, in particular regarding IL-6 RR.Table 1. Clinical features and outcomes of ATA versus PMMA. Standard deviation (SD), Interquartile range (IQR)ATA (48)PMMA (26)PAge, years, mean (SD)67.67 (15.48)69.46 (16.37).6421Male, n (%)34 (71)17 (66).7930HD age, months, median (SD)47.00 (13.75–89.75)27.50 (14.25–71.50).3653Charlson Comorbidity Index, median (IQR)4.00 (3.00–5.00)5 (3.00 –7.25).2549Arteriovenous Fistula, n (%)39 (81)14 (54).0166Central venous catheter, n (%)9 (9)12 (46)Interstitial pneumonia, n (%)29 (60)20 (77).2008Pre-HD IL-6 pg/mL, median (IQR)14.50 (5.75–41.43)13.90 (5.80–34.10).6386IL-6 RR%, median (IQR)17.08 (−9.0–40.0)2.95 (−34.63–27.32)<0.001IL-6 RR% based on pre-dialysis IL-6 level (median, IQR) 1st tertile23.55 (−8.96–47.40)3.72 (−51.66–30.08).0013 2nd tertile16.69 (−9.79–39.39)2.18 (−24.03–25.95).0405 3rd tertile12.99 (−8.73–35.75)1.14 (−34.70–31.33).0501CRP RR%, median (IQR)7.77 (2.47–13.77)4.80 (−2.65–11.38).0017PCT RR%, median (IQR)77.38 (70.92–82.97)54.59 (42.62–63.16)<0.0001Variables at diagnosis, median (IQR) IL6 pg/mL20.30 (9.10–62.10)22.60 (9.80–56.35).8763 CRP mg/dL3.88 (0.77–143.70)3.30 (0.33–9.98).4134 PCT pg/mL1.60 (0.72–2.77)0.95 (0.53–1.48).0388Death, n (%)8 (17)5 (19).7604Table 2. Multiple logistic regression with IL-6 RR > 25% as outcome. Odds Ratio (OR), Confidence interval (CI)OR95% CIpATA1.8911.273–2.840.0018IL-6 pre-HD1.0031.001–1.007.0123CRP pre-HD0.91010.8682–0.9496< 0.0001PCT pre-HD0.95280.8644–1.008.2270Ferritin1.0000.9998–1.000.7697

Safety of Intradialytic Bamlanivimab/Etesevimab Administration in Two COVID-19 Dialysis Outpatients.

Chronic hemodialysis patients are at high risk of severe COVID-19 disease and death related to the infection. Anti-spike monoclonal antibodies administration reduces risk of disease progression and hospitalization in high-risk subjects but no clear data on end-stage renal disease are available. We report 2 cases of Bamlanivimab/Etesevimab administration to two not hospitalized chronic hemodialysis patients with SARS-CoV2 infection. Since they are large molecules (human immunoglobulin G1) with molecular weight of 146,000 Da, administration was conducted during the second hour of the dialysis session with no adverse reaction. Conclusions: Intradialytic administration of Bamlanivimab/Etesevimab could be considered safe and may allow adequate clinical observation time without hospital-stay prolongation.

Safety of intermediate dose of low molecular weight heparin in COVID-19 patients.

Coagulopathy represents one of the most important determinants of morbidity and mortality in coronavirus disease-19 (COVID-19). Whether standard thromboprophylaxis is sufficient or higher doses are needed, especially in severe patients, is unknown. To evaluate the safety of intermediate dose regimens of low-weight molecular heparin (LWMH) in COVID-19 patients with pneumonia, particularly in older patients. We retrospectively evaluated 105 hospitalized patients (61 M, 44 F; mean age 73.7 years) treated with subcutaneous enoxaparin: 80 mg/day in normal weight and mild-to-moderate impair or normal renal function; 40 mg/day in severe chronic renal failure or low bodyweight (< 45 kg); 100 mg/day if bodyweight was higher than 100 kg. All the patients had radiologically confirmed pneumonia and 63.8% had severe COVID-19. None of the patients had fatal haemorrhage; two (1.9%) patients had a major bleeding event (one spontaneous hematoma and one gastrointestinal bleeding). Only 6.7% of patients needed transfusions of red blood cells. One thrombotic event (pulmonary embolism) was observed. When compared to younger patients, patients older than 85 years had a higher mortality (40% vs 13.3%), but not an increased risk of bleeding or need for blood transfusion. The use of an intermediate dose of LWMH appears to be feasible and data suggest safety in COVID-19 patients, although further studies are needed.