Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19

Abstract

Objectives: Cytokine release syndrome (CRS) is a potentially severe complication of COVID-19 most commonly resulting in respiratory failure. This ten-patient study was designed to determine the efficacy of therapeutic plasma exchange (TPE) in improving oxygenation and in reducing the cytokine load in a critically ill subset of patients.

Methods: Five single volume plasma exchanges over eight days within a 14-day study period. In mechanically ventilated patients, oxygenation was measured via the PaO2/FiO2 (P/F) ratio and the oxygenation index (OI) daily for 14 days. Supplemental oxygen requirements were tracked daily for non-ventilated patients.

Results: Non-ventilated patients were liberated from supplemental oxygen after TPE. The response was rapid with an 87% average reduction in oxygenation requirements following and average time to return to room air of 5.25 days. All mechanically ventilated patients demonstrated improvement in oxygenation with a 78% average improvement in the P/F ratio and a 43% improvement in OI. C-reactive protein (CRP) and serum levels of IL-6, IL-8, IL-10, TNFα, IFNγ and GM-CSF, were measured daily with immediate post TPE levels drawn on days 1, 2, 4, 6 and 8. All patients demonstrated significant reductions in CRP, IL-6, IL-10 and TNFα.

Conclusions: In the majority of patients with Penn class 3 and 4 CRS complicating COVID-19, TPE demonstrated a prompt improvement in oxygenation and reduction in cytokine load without compromising patient safety. As this pilot study was envisioned to be hypothesis generating, expanded trials using TPE alone and in conjunction with novel pharmacologic agents are warranted.

Registration: ClinicalTrials.gov NCT04374149.

Keywords: COVID-19; Cytokine release syndrome; Oxygenation; Respiratory failure; Therapeutic benefit; Therapeutic plasma exchange.

Fig. 1

Two-sample Median Comparisons for CRP and Cytokine Levels. The median of CRP and cytokine levels was compared in all ten patients following the second and fifth (final) plasma exchange and at day 14. ^a Non-cardiac (inflammatory) CRP reference range. ^b Cytokine levels represent average concentrations + standard deviation [Kim et al. J TranslMed 9,113 (2011) https://doi.org/10.1186/1479-5876-9-113].