Therapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release syndrome; a retrospective propensity matched control study

Abstract

Background Cytokine release syndrome (CRS) plays a pivotal role in the pathophysiology and progression of Coronavirus disease-2019 (COVID-19). Therapeutic plasma exchange (TPE) by removing the pathogenic cytokines is hypothesized to dampen CRS. Objective To evaluate the outcomes of the patients with COVID-19 having CRS being treated with TPE compared to controls on the standard of care. Methodology Retrospective propensity score-matched analysis in a single centre from 1st April to 31st July 2020. We retrospectively analyzed data of 280 hospitalized patients developing CRS initially. PSM was used to minimize bias from non-randomized treatment assignment. Using PSM 1:1, 90 patients were selected and assigned to 2 equal groups. Forced matching was done for disease severity, routine standard care and advanced supportive care. Many other Co-variates were matched. Primary outcome was 28 days overall survival. Secondary outcomes were duration of hospitalization, CRS resolution time and timing of viral clearance on Polymerase chain reaction testing. Results After PS-matching, the selected cohort had a median age of 60 years (range 32–73 in TPE, 37–75 in controls), p = 0.325 and all were males. Median symptoms duration was 7 days (range 3–22 days’ TPE and 3–20 days controls), p = 0.266. Disease severity in both groups was 6 (6.6%) moderate, 40 (44.4%) severe and 44 (49%) critical. Overall, 28-day survival was significantly superior in the TPE group (91.1%), 95% CI 78.33–97.76; as compared to PS-matched controls (61.5%), 95% CI 51.29–78.76 (log rank 0.002), p<0.001. Median duration of hospitalization was significantly reduced in the TPE treated group (10 days vs 15 days) (p< 0.01). CRS resolution time was also significantly reduced in the TPE group (6 days vs. 12 days) (p< 0.001). In 71 patients who underwent TPE, the mortality was 0 (n = 43) if TPE was done within the first 12 days of illness while it was 17.9% (deaths 5, n = 28 who received it after 12th day (p = 0.0045). Conclusion An earlier use of TPE was associated with improved overall survival, early CRS resolution and time to discharge compared to SOC for COVID-19 triggered CRS in this selected cohort of PS-matched male patients from one major hospital in Pakistan.

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

“…28‐day mortality was 21.4% and 28.6%, respectively. Kamran et al retrospectively analyzed 280 COVID‐19 patients [19]. Seventy‐one patients underwent PE and 209 patients did not.…”

COVID-19 Sepsis: Pathogenesis and Endothelial Molecular Mechanisms Based on “Two-Path Unifying Theory” of Hemostasis and Endotheliopathy-Associated Vascular Microthrombotic Disease, and Proposed Therapeutic Approach with Antimicrothrombotic Therapy

“…Despite of uncommon hematologic and hemostatic complications, ARDS has been a life-threatening clinical phenotype of EA-VMTD. A retrospective propensity matched control study showed improved survival of serious COVID-19 patients with therapeutic plasma exchange (TPE), 37 which supports the benefit from indirect supply of the protease ADAMTS13 even without TTP-like syndrome. Considering these findings and data in COVID-19, “EA-VMTD” should stand as the diagnostic term of choice representing endotheliopathy with or without TTP-like syndrome.…”

“…MODS often occurs with inflammation. 15 , 18 , 37 , 44 , 45 Sometimes it is called cytokine storm in severe case. This additional activation of inflammatory pathway had been predicted to occur according to “two-activation theory of the endothelium“ as shown in Figure 3 .…”

“…TPE was employed for the treatment of COVID-19 and had shown improved overall survival in a good retrospective case control study. 37 The benefit was claimed to be the result of removal of cytokines, but the decreased mortality was more likely from the result of replenished ADAMTS13 that had counteracted microthrombogenesis.…”

“…It has shown promising result in case series, and clinical trials are in progress for COVID-19. 37 , 129–134 Since ARDS is caused by microthrombosis and often advances to various organ phenotypes due to disseminated microthrombosis, TPE may become a valuable therapeutic regimen in most of patients with early stage of ARDS and other organ syndromes. The main drawback is that TPE may not be readily available in many patient care centers, and is very time-consuming and labor-intensive procedure.…”