ABSTRACT
IMPORTANCE: Recent evidence suggests a multilevel inflammatory syndrome as a driving factor in some of the most severely ill coronavirus disease 2019 patients with overlapping features to other hyperinflammatory or autoimmune diseases. Therefore, plasma exchange is considered as potential therapy in these patients. OBJECTIVES: We characterize the longitudinal therapeutic efficacy and safety profile of plasma exchange in critically ill patients with clinical and laboratory evidences of coronavirus disease 2019-related immunopathology. DESIGN SETTING AND PARTICIPANTS: A retropsective case-control study of critically ill coronavirus disease 2019 patients treated with plasma exchange at Heidelberg University Hospital between March and December 2020. Plasma exchange-treated patients were compared with coronavirus disease 2019 patients on standard therapy matched for age, gender, disease severity, and features of hyperinflammatory syndrome. MAIN OUTCOME AND MEASURES: Mortality rate and course of clinical and laboratory parameters in response to plasma exchange were assessed in coronavirus disease 2019 patients and in patients on standard care. A plasma volume of 50 mL per kg body weight or a maximum of 4 L was exchanged. RESULTS: In total, 28 critically ill coronavirus disease 2019 patients were treated with a median of three plasma exchange procedures per patient. No relevant complications occurred during plasma exchange therapy. Inflammatory and biochemical markers of end-organ damage and endothelial activation were significantly reduced following plasma exchange together with normalization of body temperature, improved pulmonary function, and reduced vasopressor demand. Most importantly, these improvements were maintained after the last plasma exchange. In contrast, no such effects were observed in the control group, although baseline clinical and laboratory parameters were comparable. Kaplan-Meier analysis showed improved 30-day survival in the plasma exchange group compared with 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 plasma exchange versus standard care. CONCLUSIONS AND RELEVANCE: Our data provide further evidence for plasma exchange as a novel therapeutic strategy in a subset of critically ill coronavirus disease 2019 patients by potentially reversing the complex coronavirus disease 2019 immunopathology. Randomized controlled trials are underway to confirm these positive results.
ABSTRACT
Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses an enormous challenge to health care systems throughout the world. Without causal treatment, identification of modifiable prognostic factors may help to improve outcomes. To explore possible associations of vitamin D (VitD) status with disease severity and survival, we studied 185 patients diagnosed with coronavirus disease 2019 (COVID-19) and treated at our center. VitD status at first presentation was assessed retrospectively using accredited laboratory methods. VitD deficiency was defined as serum total 25-hydroxyvitamin D level < 12 ng/mL (<30 nM). Primary endpoint was severe course of disease (i.e., need for invasive mechanical ventilation and/or death, IMV/D). Within a median observation period of 66 days (range 2-92), 23 patients required IMV. A total of 28 patients had IMV/D, including 16 deaths. Ninety-three (50%) patients required hospitalization (inpatient subgroup). A total of 41 (22%) patients were VitD deficient. When adjusted for age, gender, and comorbidities, VitD deficiency was associated with higher risk of IMV/D and death (HR 6.12, 95% CI 2.79-13.42, p < 0.001 and HR 14.73, 95% CI 4.16-52.19, p < 0.001, respectively). Similar correlations were observed in the inpatient subgroup. Our study demonstrates an association between VitD deficiency and severity/mortality of COVID-19, highlighting the need for interventional studies on VitD supplementation in SARS-CoV-2 infected individuals.