Early Initiation of Extracorporeal Blood Purification Using the AN69ST (oXiris®) Hemofilter as a Treatment Modality for COVID-19 Patients: a Single-Centre Case Series

Abstract

Introduction: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support.

Methods: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds.

Results: Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (< 50 ng/mL), and a decrease of CRP and fibrinogen.

Conclusion: Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.

Keywords: Blood Platets; C-Reactive Protein; COVID-19; Cytokines; Heparin; Interleukin-6; Respiratory Distress Syndrome, Adult; Respiratory Rate; TNF protein, human; Tumor Necrosis Factor-alpha.

Fig. 1

STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) diagram. COVID-19=coronavirus disease 2019; CRP=C-reactive protein; HGB/HCT=hemoglobin/hematocrit; ICU=intensive care unit; IL=interleukin; NLR=neutrophil-to-lymphocyte ratio; RT-PCR=reverse transcription polymerase chain reaction; SII=systemic immune-inflammation index, thrombocyte*(neutrophil-to-lymphocyte); TNF-α=tumour necrosis factor alpha

Fig. 2

Treatment protocol for coronavirus disease 2019 patients. In addition to blood purification, systemic heparinisation, and physical therapy under continuous positive airway pressure (CPAP), the general care protocol consisted of rest and recovery; sufficient caloric intake and adequate electrolyte balance; aggressive rehydration in the first 24 hours; parenteral, enteral nutrition for mechanically ventilated patients; low-dose Dexamethasone therapy (8 mg/24 hours), antibiotic therapy, and biochemical and chest X-ray imaging for monitoring. ACT=activation clotting time; CRP=C-reactive protein; IL=interleukin; NLR=neutrophil-to-lymphocyte ratio; SpO2=oxygen saturation; TNF-α=tumour necrosis factor alpha

Fig. 3

Pre- and post-treatment X-ray images. (A) 62-year-old male (Figure 6M) was admitted with oxygen saturation (SpO2) of 93%, fatigue, and breathing difficulties. Before his admission, he had several episodes of high body temperature (39 °C). Chest radiography on admission showed bilateral patchy reticular areas of opacifications, perihilar and peripheral distribution with lower zone predominance, and subsegmental atelectasis in the mid-zone of the left lung. (B) Control X-ray showing minor regression of baseline findings. (C) A 67-year-old male with severe coronavirus disease 2019 (COVID-19) was admitted with breathing difficulties, SpO2 of 85%, and Staphylococcus aureus (cytokine profile shown in Figure 6F); we noted patchy bilateral areas of opacifications with lower zone predominance, right perihilar, and left peripheral distribution. (D) We discharged him after 10 days with significantly improved SpO2 96% and regression of X-ray findings. (E) We admitted a 70-year-old hypertensive febrile (38 ºC) female (Figure 6I) with SpO2 of 85%, dyspnoea, tachypnoea, and COVID-19 pneumonia; we observed bilateral reticulonodular areas of opacifications with perihilar and peripheral distribution, with consolidation in the upper right lung and evidence of right pleural effusion. Her condition was complicated because of Klebsiella pneumoniae, Streptococcus beta haemolyticus co-infection in respiratory samples, and vancomycin-resistant Enterococcus in urine samples taken within 24 after admission. At discharge, we observed minimal regressions in findings of consolidation and resolution of the right pleural effusion (F). Panel (G) shows the first X-ray image taken of a 51-year-old male (Figure 6J); chest X-ray findings point to bilateral perihilar and peripheral extensive patchy opacifications and a prominent zone of consolidation in the mid- and upper peripheral section, the left lobe was more affected. (H) Treatment resulted in the normalisation of peripheral oxygen saturation values. Still, X-ray images suggested a minor progression of initial findings; non-resolving bilateral consolidations with bigger consolidation zone in the left upper peripheral lung. Panel (I) shows patchy bilateral consolidations, perihilar and peripheral distribution, of a 50-year-old male (Figure 6B) admitted with a SpO2 of 92% and previous episodes of high body temperature. He received two cycles of oXiris® blood purification and on the explicit, consented request of his family and relatives he was also treated with 8 mg/kg Tocilizumab given over 120 minutes via intravenous infusion. (J) Chest X-rays showed progression; bilateral consolidations, pleural effusion, and small apical pneumothorax in the right lobe. He was initially treated with Azithromycin which was adapted to Ciprofloxacin after multiplex reverse transcription-polymerase chain reaction identified Staphylococcus aureus and Klebsiella pneumoniae; he was discharged after 15 days.

Fig. 4

Biochemical parameters during hospitalisation. Graphs present an overview of selected biochemical parameters monitored for coronavirus disease 2019 severity. Red lines show a general trendline during hospitalisation. The red coloured symbols pertain a patient who succumbed as a result of acute respiratory distress syndrome. The coloured (red #1) (purple #2) symbols show the values for the two mortality cases. ALT=alanine aminotransferase; AST=aspartate aminotransferase; CRP=C-reactive protein; HCT=hematocrit; HGB=hemoglobin; WBC=white blood cell

Fig. 5

Analysis of coagulation markers. Patients receive an initial 25000 international units (IU) bolus injection (≈ 300 IU/kg) followed by continuous infusion of 300 IU/kg dissolved in physiological buffer (0.9% sodium chloride) administered at 6-8 mL/h flow rate; target activation clotting time ≥ 200 s during hospitalisation. Patients' coagulation statuses were tracked by evaluating fibrinogen, D-Dimers, and the international normalised ratio (INR). The coloured (red #1) (purple #2) symbols show the values for the two mortality cases.

Fig. 6

Inflammatory mediator analysis; systemic levels of interleukin (IL)-6, IL/chemokine (C-X-C motif ) ligand 8 (CXCL-8), and tumour necrosis factor alpha (TNF-α). Individual cytokine profile (A - O) IL-6, IL-8, and TNF-α are plotted on the left y-axis (pg/mL), and C-reactive protein (CRP) is plotted on the right y-axis (mg/L). The start of oXiris® hemofiltration 24-cycle is shown on the x-axis. One patient (Panel B) also received Tocilizumab (= anti-IL-6 receptor mAb). Cytokine data are plotted on the left y-axis; CRP (grey checkered line) values are plotted on the right y-axis. Panels (P, Q, and R) show combined data during hospitalisation for IL-6, IL-8, and TNF-α. The coloured (red #1) (purple #2) symbols show the values for the two mortality cases.

Supplemental Figure 1

(A) A 73-year-old male coronavirus disease 2019 (COVID-19) patient was admitted for urgent surgery; at admission, he was in hemorrhagic shock. Computed tomography (CT) revealed a ruptured infrarenal 10-cm aneurysm of the abdominal aorta. Radiography confirmed bilateral pneumonia. Despite successful surgery, his clinical condition was unstable, requiring increasing catecholamine support. Extracorporeal blood purification was initiated on the 3rd postoperative course. The approach was unable to reverse the clinical deterioration, he developed multiorgan failure and passed away in the early hours of the 4th postoperative day. (B) A 55-year-old patient with confirmed reverse transcription polymerase chain reaction for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and mild COVID-19 symptoms was hospitalised at our emergency room with abdominal complaints, most pronounced in the epigastric region, CT pointed to a ruptured infrarenal aneurysm of the abdominal aorta with a diameter of about 7 cm. The aneurysm was treated with an AlboGraft® prosthesis followed with a blood purification cycle on the 1st postoperative day. In the subsequent five days, he tested twice negative for SARS-CoV-2. He was discharged on the 6th postoperative day in stable condition; follow-up after 30 days of the procedure confirmed his clinical recovery. CRP=C-reactive protein; CXCL-8=chemokine (C-X-C motif ) ligand 8; IL=interleukin; TNF-α=tumour necrosis factor alpha