We read with interest the report by Lin et al. that was recently published in the journal.1 The authors are to be congratulated for their excellent work. Our group's interest about the putative benefit of therapeutic plasma exchange (TPE) in critically ill patients with SARS-CoV-2 disease (COVID-19) has been documented.2 In a minority of patients, COVID-19 can present with life-threatening features such as acute respiratory distress syndrome (ARDS), septic shock, thromboembolic disease, multi-system organ failure, and associated cytokine release syndrome (CRS). The latter is defined by criteria outlined in Table 1 .3 Elevated levels of inflammatory biomarkers and lymphocytopenia are early predictors of severe COVID-19 pneumonia with extensive lung parenchymal involvement and death.
Table 1.
Criteria for defining cytokine release syndrome in COVID-19.
| One or more of the following criteria should be presenta |
| C-reactive protein >100 or >50 mg/L but doubled in the past 48 h |
| lymphocyte count <0.6 × 109/L |
| Serum Interleukin-6 (IL-6) ≥ 3× upper normal limit |
| Ferritin >300 ug/L (or surrogate) with doubling within 24 h |
| Ferritin >600 ug/L at presentation and LDH >250 U/L |
| Elevated D-dimer (>1 mcg/mL) |
Abbreviations: CRS = cytokine release syndrome, LDH = lactate dehydrogenase.
We define as low risk for developing CRS the presence of one criterion, moderate risk the presence of two to three criteria and high risk the presence of more than three criteria.
In the Lin et al. study, the development of acute respiratory failure and sepsis, 15 days after hospital admission, could have been attributed to a hospital acquired bacterial infection although the resurgence of COVID-19 cannot be definitely excluded. In our experience, CRS usually presents rather early in the clinical course of COVID-19 and is associated with high Sequential Organ Failure Assessment scores and grave prognosis. In our practice, TPE is performed by means of the Spectra Optia ™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA), and operating with acid-citrate dextrose anticoagulant as per Kidney Disease Improving Global Outcomes 2019 guidelines. The adsorption cartridge contains activated uncoated coconut shell (carbon granules) charcoal (100 gm), and the nonionic resins Amberlite XAD-7HP and Amberchrom GC300C. These adsorption materials could remove significant proportions of interferon-gamma, interleukins −3, −10, −1 B, −6, −8, and tumor necrosis factor-alpha.4 Our preliminary results have been promising in treating patients with life-threatening COVID-19 and associated CRS.
TPE can be performed with a variety of adsorption cartridges and has been the subject of well-known clinical trials.5 Although SARS-CoV-2 is a respiratory virus, COVID-19 can be interpreted as a clinical syndrome with various cardiovascular, neurological, hematological and other manifestations. The suppression of CRS may be a key therapeutic step in the management of critically ill COVID-19 patients. Reducing cytokines, especially interleukin-6, warrants further attention. A monoclonal antibody against iterleukin-6 (tocilizumab) has been recently used in COVID-19 but with conflicting results. The benefit of TPE is still uncertain in severe ARDS due to COVID-19. Also, the natural course of SARS-CoV-2's viremia remains obscure. Hence, the relationship between viral RNA reduction and TPE, and the standardization of the TPE regime need to be further investigated.
Role of funding source
No financial support was received for this study.
Ethics committee approval
The study was approved by our Institutional Review Board (protocol/serial number: H-01-R-053, IORG0010374, H1R1-20-01TYGH-109-05).
Declaration of Competing Interest
All authors have no conflicts of interest relevant to this article.
References
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