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 .

What Is the Role of Therapeutic Plasma Exchange as an Adjunctive Treatment in Severe COVID-19: A Systematic Review

“…After excluding some of the articles for numerous reasons, the final 18 papers were included in the systematic review. The most common types of studies were case-series studies ( n = 14) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], then case-control studies ( n = 2) [ 17 , 35 ] and a propensity score matched study [ 36 ]. Only one randomized controlled trial was included in the analysis [ 37 ].…”

“…Out of 384 patients, 220 received TPE. The number of patients in the studies varied from 3 to 90 with a median of 8 patients (IQR 5–18) [ 17 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The mean or the median age of participants in seven studies was below 65 years [ 8 , 10 , 11 , 12 , 13 , 14 , 15 ], whereas in the remaining four studies, it was above 65 years [ 5 , 6 , 7 , 9 ].…”

Plasma Exchange to Rescue Patients with Autoantibodies Against Type I Interferons and Life-Threatening COVID-19 Pneumonia

“…Finally, the precise timing of such treatment, if effective, remains to be determined. Indeed, in addition to removing auto-Abs against type I IFNs, PE in COVID-19 patients could theoretically act on various targets, thereby affecting coagulation [ 18 ], inflammatory mediators [ 6 , 7 ], or antiviral innate immunity, as described here. The timing of PE may, therefore, be crucial: for the removal of auto-Abs against type I IFNs and the restoration of type I IFN antiviral immunity, treatment should probably be performed earlier in the course of the disease, when the virus is still in the early phases of replication, viral load is highest, and the patients have not yet become critically ill.…”

Combination therapy with plasma exchange and glucocorticoid may be effective for severe COVID‐19 infection: A retrospective observational study

“…Liu et al reported that PE was used in 9 of 23 patients admitted to the ICU and a decrease in blood cytokines after PE [14]. Gluck et al performed five sessions of PE over 8 days in 10 patients with increased oxygen demand [15]. Ventilated patients also reported an average 78% improvement in PaO 2 /FiO 2 ratio, and significant decreases in blood levels of CRP and cytokines.…”