Background We sought to clarify the benefit of cytokine adsorption in patients with COVID-19 supported with venovenous extracorporeal membrane oxygenation (ECMO).Methods We did a single-centre, open-label, randomised, controlled trial to investigate cytokine adsorption in adult patients with severe COVID-19 pneumonia requiring ECMO. Patients with COVID-19 selected for ECMO at the Freiburg University Medical Center (Freiburg, Germany) were randomly assigned (1:1) to receive cytokine adsorption using the CytoSorb device or not. Randomisation was computer-generated, allocation was concealed by opaque, sequentially numbered sealed envelopes. The CytoSorb device was incorporated into the ECMO circuit before connection to the patient circuit, replaced every 24 h, and removed after 72 h. The primary endpoint was serum interleukin-6 (IL-6) concentration 72 h after initiation of ECMO analysed by intention to treat. Secondary endpoints included 30-day survival. The trial is registered with ClinicalTrials.gov (NCT04324528) and the German Clinical Trials Register (DRKS00021300) and is closed. Findings From March 29, 2020, to Dec 29, 2020, of 34 patients assessed for eligibility, 17 (50%) were treated with cytokine adsorption and 17 (50%) without. Median IL-6 decreased from 357•0 pg/mL to 98•6 pg/mL in patients randomly assigned to cytokine adsorption and from 289•0 pg/mL to 112•0 pg/mL in the control group after 72 h. One patient in each group died before 72 h. Adjusted mean log IL-6 concentrations after 72 h were 0•30 higher in the cytokine adsorption group (95% CI −0•70 to 1•30, p=0•54). Survival after 30 days was three (18%) of 17 with cytokine adsorption and 13 (76%) of 17 without cytokine adsorption (p=0•0016).Interpretation Early initiation of cytokine adsorption in patients with severe COVID-19 and venovenous ECMO did not reduce serum IL-6 and had a negative effect on survival. Cytokine adsorption should not be used during the first days of ECMO support in COVID-19.Funding None.

The novel coronavirus SARS-CoV-2 and the resulting disease COVID-19 causes pulmonary failure including severe courses requiring venovenous extracorporeal membrane oxygenation (V-V ECMO). Coagulopathy is a known complication of COVID-19 leading to thrombotic events including pulmonary embolism. It is unclear if the coagulopathy also increases thrombotic circuit complications of the ECMO. Aim of the present study therefor was to investigate the rate of V-V ECMO complications in COVID-19. We conducted a retrospective registry study including all patients on V-V ECMO treated at our centre between 01/2018 and 04/2020. COVID-19 cases were compared non-COVID-19 cases. All circuit related complications resulting in partial or complete exchange of the extracorporeal system were registered. In total, 66 patients were analysed of which 11 (16.7%) were SARS-CoV-2 positive. The two groups did not differ in clinical parameters including age (COVID-19 59.4 vs. non-COVID-19 58.1 years), gender (36.4% vs. 40%), BMI (27.8 vs. 24.2) and severity of illness as quantified by the RESP Score (1pt. vs 1pt.). 28 days survival was similar in both groups (72.7% vs. 58.2%). While anticoagulation was similar in both groups (p = 0.09), centrifugal pump head thrombosis was more frequent in COVID-19 (9/11 versus 16/55 p < 0.01). Neither the time to first exchange (p = 0.61) nor blood flow at exchange (p = 0.68) did differ in both groups. D-dimer levels prior to the thrombotic events were significantly higher in COVID-19 (mean 15.48 vs 26.59, p = 0.01). The SARS-CoV-2 induced infection is associated with higher rates of thrombotic events of the extracorporeal system during V-V ECMO therapy. Keyword V-V ECMO • COVID-19 • Thrombotic complications • Pump head thrombosis Abbreviations aPTT Activated partial thromboplastin time ARDS Acute respiratory distress syndrome COVID-19 Coronavirus disease 2019 ICU Intensive care unit SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 V-V ECMO Venovenous extracorporeal membrane oxygenation Highlights • This study compared the rate of thrombotic circuit complications in COVID-19 V-V ECMO patients to historical controls. • The two groups were comparable.

Background: Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with venovenous extracorporeal membrane oxygenation (VV ECMO) support. Methods: We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. Patients were allocated to the PP group if PP was performed during VV ECMO treatment or the supine positioning group. VV ECMO weaning success and hospital survival were analysed before and after propensity score matching. Results: A total of 158 patients could be analysed, and 38 patients (24.1%) received PP. There were no significant differences in VV ECMO weaning rate (47.4% vs. 46.7%, p = 0.94) and hospital survival (36.8% vs. 36.7%, p = 0.98) between the prone and supine groups, respectively. The analysis of 38 propensity score matched pairs also showed no difference in hospital survival (36.8% vs. 36.8%, p = 1.0) or VV ECMO weaning rate (47.4% vs. 44.7%, p = 0.82). Hospital survival was superior in the subgroup of patients treated with early PP (cutoff < 17 h via Youden's Index) as compared to late or no PP (81.8% vs. 33.3%, p = 0.02). Conclusion: In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. However, early initiation of prone positioning was linked to a significant reduction of hospital mortality.