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.

BackgroundWhole body ischemia-reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) induces a generalized inflammatory response which contributes to the development of post-cardiac arrest syndrome (PCAS). Recently, pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and inflammasomes, have been shown to mediate the inflammatory response in IRI. In this study we investigated monocyte PRR signaling and function in PCAS.MethodsBlood samples were drawn in the first 12 hours, and at 24 and 48 hours following return of spontaneous circulation in 51 survivors after cardiac arrest. Monocyte mRNA levels of TLR2, TLR4, interleukin-1 receptor-associated kinase (IRAK)3, IRAK4, NLR family pyrin domain containing (NLRP)1, NLRP3, AIM2, PYCARD, CASP1, and IL1B were determined by real-time quantitative PCR. Ex vivo cytokine production in response to stimulation with TLR ligands Pam3CSK4 and lipopolysaccharide (LPS) was assessed in both whole blood and monocyte culture assays. Ex vivo cytokine production of peripheral blood mononuclear cells (PBMCs) from a healthy volunteer in response to stimulation with patients’ sera with or without LPS was assessed. The results were compared to 19 hemodynamically stable patients with coronary artery disease.ResultsMonocyte TLR2, TLR4, IRAK3, IRAK4, NLRP3, PYCARD and IL1B were initially upregulated in patients following cardiac arrest. The NLRP1 and AIM2 inflammasomes were downregulated in resuscitated patients. There was a significant positive correlation between TLR2, TLR4, IRAK3 and IRAK4 expression and the degree of ischemia as assessed by serum lactate levels and the time until return of spontaneous circulation. Nonsurvivors at 30 days had significantly lower mRNA levels of TLR2, IRAK3, IRAK4, NLRP3 and CASP1 in the late phase following cardiac arrest. We observed reduced proinflammatory cytokine release in response to both TLR2 and TLR4 activation in whole blood and monocyte culture assays in patients after CPR. Sera from resuscitated patients attenuated the inflammatory response in cultured PBMCs after co-stimulation with LPS.ConclusionsSuccessful resuscitation from cardiac arrest results in changes in monocyte pattern recognition receptor signaling pathways, which may contribute to the post-cardiac arrest syndrome.Trial registrationThe trial was registered in the German Clinical Trials Register (DRKS00009684) on 27/11/2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1340-3) contains supplementary material, which is available to authorized users.

Systemic inflammation is a major feature of the post-cardiac arrest syndrome. The three monocyte subpopulations are thought to play an important role in this inflammatory state because they are endowed with numerous pattern recognition receptors, such as CD14, that have been associated with ischemia–reperfusion injury. By contrast, an exaggerated antiinflammatory response has also been described following cardiac arrest, which may be mediated by downregulation of antigen presentation receptor HLA-DR. We report the composition of monocyte subpopulations and the expression of CD14 and HLA-DR following cardiac arrest. Blood specimens were collected from 32 patients at three timepoints in the first 48 h after cardiac arrest. Monocyte subset composition was determined by flow cytometry based on the expression of CD14, CD16, and HLA-DR. Monocyte subset composition and the expression of CD14 and HLA-DR were correlated with patient outcomes. The results were compared to 19 patients with coronary artery disease. Cardiac arrest patients showed a significant decline in the percentage of nonclassical monocytes. Monocyte CD14 expression was upregulated after 24 h and correlated with the time to return of spontaneous circulation. Downregulation of HLA-DR expression was observed mainly among classical monocytes and significantly correlated with the dose of norepinephrine used to treat shock. Downregulation of HLA-DR among nonclassical and intermediate monocytes was significantly associated with disease severity. Our data demonstrate the disturbance of monocyte subset composition with a significant decline in nonclassical monocytes at an early stage following cardiac arrest. Our findings suggest the simultaneous presence of hyperinflammation, as evidenced by upregulation of CD14, and monocyte deactivation, characterized by downregulation of HLA-DR. The extent of monocyte deactivation was significantly correlated with disease severity.