Plasma exchange to treat patients with severe COVID-19

Background: The clinical spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to critical illness and death in up to 89% of mechanically ventilated patients. Therefore, new therapeutic strategies are needed. Recent evidence suggests a multi-level inflammatory syndrome in some of the most critically ill patients with overlapping features of other hyperinflammatory or autoimmune diseases. Thus, plasma exchange (PE) has become a subject of controversy as potential therapy in these patients. Here, we report the results of the so far largest cohort of critically ill COVID-19 patients treated with PE. Methods: All critically ill COVID-19 patients treated with PE at Heidelberg University Hospital were analyzed between April and December 2020. Disease course and outcomes were compared with a standard care control group matched for age, sex, and disease severity. Changes in laboratory and clinical parameters were studied longitudinally. Kaplan-Meier and Cox regression analyses were performed. Results: In total, 28 critically ill COVID-19 patients were treated with an average of 3 PE procedures per patient. No relevant complications occurred during PE therapy. Inflammatory markers and biochemical indicators of end-organ damage and endothelial activation were significantly reduced during PE. These laboratory changes were accompanied by normalization of body temperature, improved pulmonary function, and reduced vasopressor demand. Most importantly, the laboratory and clinical improvements were maintained after the last PE. In contrast, most parameters in the control group did not improve significantly over seven days, although baseline clinical and laboratory parameters were comparable in both groups. Kaplan-Meier analysis showed improved 30-day survival in the PE group compared to the control group (67.9% vs. 42.9%, p=0.044). In a multivariable analysis, the hazard ratio for death was 0.27 (95% CI 0.11-0.68, p=0.005) with PE versus standard care. Conclusions: Our data further suggest that PE represents a potential therapeutic strategy for a subset of severe COVID-19 cases. The observed PE-related effects appear to go beyond a purely artificial improvement in blood parameters and may indicate a reversal of the complex COVID-19 immunopathology. Randomized controlled trials are urgently needed.