key: cord-1000029-04mlf0b8
authors: Monneret, Guillaume; Benlyamani, Ihsane; Gossez, Morgane; Bermejo‐Martin, Jesus F; Martín‐Fernandez, Marta; Sesques, Pierre; Wallet, Florent; Venet, Fabienne
title: COVID‐19: What type of cytokine storm are we dealing with?
date: 2020-07-27
journal: J Med Virol
DOI: 10.1002/jmv.26317
sha: 56054d87426d8bdc1a8528bdefb2ec8929b7bd3c
doc_id: 1000029
cord_uid: 04mlf0b8

We read with great interest the comment published by Andrianopoulos et al. in which the authors advocate for cautious use of tocilizumab in COVID-19 patients 1 . Tocilizumab is a monoclonal antibody against the interleukin-6 receptor which has immunosuppressive properties. Whereas accumulating results from uncontrolled trials present tocilizumab as an effective agent blocker of disease progression, some contrasting studies also progressively appear in COVID-19 literature 2-5 . This muddies the waters and makes the situation more confused. This article is protected by copyright. All rights reserved.

Tocilizumab is a monoclonal antibody against the interleukin-6 (IL-6) receptor that has immunosuppressive properties. Whereas accumulating results from uncontrolled trials present tocilizumab as an effective agent blocker of disease progression, some contrasting studies also progressively appear in COVID-19 literature. [2] [3] [4] [5] This muddies the waters and makes the situation more confused. Therefore, we would like to reinforce the purpose of Of note, by recent international definition, severe COVID-19 can be classified as a viral sepsis, 8 that is, organ failure (acute respiratory distress syndrome) induced by a dysregulated response to an infection (SARS-CoV-2). In sepsis, on a general basis, anti-inflammatory strategies did not show any significant efficacy despite numerous clinical trials. 9 With that said, one study identified a protective effect of immunomodulatory treatment in a subgroup of septic patients when stratified based on circulating IL-6 values. In this study, the threshold to highlight this effect was 1000 pg/mL. 10 In conclusion, it is unquestionable that COVID-19 presents with inflammatory characteristics. As such, there is likely a room for tocilizumab (or other anti-inflammatory drugs) in subgroups of patients to avoid progression toward uncontrolled inflammation. That given,

we suggest that such treatment should be envisaged in a more individualized manner and on short period not to amplify marked immunosuppression observed in intensive care unit COVID-19 patients. 11, 12 We thus agree with Andrianopoulos et al 1 to cautiously consider tocilizumab depending on disease chronology, occurrence of ARDS, IL-6 level stratification and most importantly, the depth of lymphopenia. 

Tocilizumab's efficacy in COVID-19 patients is determined by the presence of cytokine storm

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in

Use of tocilizumab for COVID-19-induced cytokine release syndrome: a cautionary case report

Tocilizumab for treatment of severe COVID-19 patients: preliminary results from SMAtteo COvid19 REgistry (SMACORE). Microorganisms

Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: Results from a single Italian Centre study on tocilizumab versus standard of care

Elevated interleukin-6 and severe COVID-19: a meta-analysis

Disease-drug interactions in inflammatory states via effects on CYP-mediated drug clearance

The third international consensus definitions for sepsis and septic shock (sepsis-3)

Such stuff as dreams are made on: mediator-directed therapy in sepsis

Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels

Coronavirus disease 2019 as a particular sepsis: a 2-week follow-up of standard immunological parameters in critically ill patients

Severe COVID-19 is associated with deep and sustained multifaceted cellular immunosuppression

The authors declare that there are no conflict of interests.