BackgroundPatients with Coronavirus Disease (COVID-19) often develop severe acute respiratory distress syndrome (ARDS) requiring prolonged mechanical ventilation (MV), and venovenous extracorporeal membrane oxygenation (V–V ECMO).Mortality in COVID-19 patients on V–V ECMO was exceptionally high; therefore, whether survival can be ameliorated should be investigated. MethodsWe collected data from 85 patients with severe ARDS who required ECMO support at the University Hospital Magdeburg from 2014 to 2021. The patients were divided into the COVID-19 group (52 patients) and the non-COVID-19 group (33 patients). Demographic and pre-, intra-, and post-ECMO data were retrospectively recorded. The parameters of mechanical ventilation, laboratory data before using ECMO, and during ECMO were compared. ResultsThere was a significant difference between the two groups regarding survival: 38.5% of COVID-19 patients and 63.6% of non-COVID-19 patients survived 60 days (p = 0.024). COVID-19 patients required V–V ECMO after 6.5 days of MV, while non-COVID-19 patients required V–V ECMO after 2.0 days of MV (p = 0.048). The COVID-19 group had a greater proportion of patients with ischemic heart disease (21.2% vs 3%, p = 0.019). The rates of most complications were comparable in both groups, whereas the COVID-19 group showed a significantly higher rate of cerebral bleeding (23.1 vs 6.1%, p = 0.039) and lung bacterial superinfection (53.8% vs 9.1%, p = <0.001). ConclusionThe higher 60-days mortality among patients with COVID-19 with severe ARDS was attributable to superinfection, a higher risk of intracerebral bleeding, and the pre-existing ischemic heart disease.