key: cord-0722453-0ou5f158
authors: ROUMIER, Mathilde; PAULE, Romain; GROH, Matthieu; VALLEE, Alexandre; ACKERMANN, Felix
title: Interleukin-6 blockade for severe COVID-19
date: 2020-04-22
journal: nan
DOI: 10.1101/2020.04.20.20061861
sha: eec1b65d2870e77c6b20afb7872f3a5fb16e28c1
doc_id: 722453
cord_uid: 0ou5f158

In the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Following the assumption by Mehta and colleagues who exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and investigate immunomodulatory drugs in this setting, we relate our short-term - yet promising - experience regarding IL6 blockade with tocilizumab in 30 selected patients of less than 80 years of age, >5 days of prior disease duration, severe (i.e. requiring strictly over 6L/min of oxygen therapy) rapidly deteriorating (i.e. increase by more than 3L/min of oxygen flow within the previous 12 hours) COVID-19-related pneumonia. By comparison with a control group of patients (matched for age, gender and disease severity using the inverse probability of treatment weighted methodology) that did not receive tocilizumab. We demonstrate that, in highly selected patients, IL6 blockade could curb the "cytokine storm", prevent ICU admission and the requirement for mechanical ventilation. Notwithstanding the shortcomings of this retrospective small sample-size study, we believe that these preliminary findings support the fostering of research efforts in the fight against COVID-19-induced inflammation, especially before patients require admission to the ICU.

In the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Following the assumption by Mehta and colleagues who exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and investigate immunomodulatory drugs in this setting, we relate our short-term -yet promising -experience regarding IL6 blockade with tocilizumab in 30 selected patients of less than 80 years of age, >5 days of prior disease duration, severe (i.e. requiring strictly over 6L/min of oxygen therapy) rapidly deteriorating (i.e. increase by more than 3L/min of oxygen flow within the previous 12 hours) COVID-19-related pneumonia. By comparison with a control group of patients (matched for age, gender and disease severity using the inverse probability of treatment weighted methodology) that did not receive . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 22, 2020. . https://doi.org/10.1101/2020.04.20.20061861 doi: medRxiv preprint 2 tocilizumab. We demonstrate that, in highly selected patients, IL6 blockade could curb the "cytokine storm", prevent ICU admission and the requirement for mechanical ventilation.

Notwithstanding the shortcomings of this retrospective small sample-size study, we believe that these preliminary findings support the fostering of research efforts in the fight against COVID-19-induced inflammation, especially before patients require admission to the ICU. there is growing evidence that virally-induced pro-inflammatory cytokines (including Interleukin (IL)1β, IL-6, tumor necrosis factor-α, and granulocyte colony stimulating factor) lead to both hyperinflammatory and procoagulatory states at a late-stage of the disease (1, 2) . Such findings are further corroborated by recent studies, which highlighted that high levels of C-reactive protein, IL-6 and D-Dimer upon admission were predictors of mortality (3, 4) . In their recent Comment, Mehta and colleagues exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and suggested that immunosuppressive and/or immunomodulatory drugs should be investigated in this setting (5) . Here, we relate our short-term -yet promising -experience regarding IL6 blockade for severe COVID-19 with tocilizumab.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 22, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 22, 2020. were discharged from the ICU and from hospital, respectively. Overall, tocilizumab was well-tolerated, yet mild hepatic cytolysis (n=2) and ventilator-acquired pneumonia (n=1) were reported. Of note, 2 patients treated with tocilizumab also received a 10-day course of hydroxychloroquine (200mg tid) and azithromycin (250mg bid on day1 and qid thereafter), while 2 patients (that were not treated with tocilizumab) received high-dose (≥1mg/kg/d) methylprednisolone pulses.

In the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Concordant with the assumption by Mehta (5) and others (8) , these data suggest that targeting IL-6 in highly selected patients with rapidly deteriorating pneumonia and high inflammatory parameters could curb the "cytokine storm", prevent is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 22, 2020. . https://doi.org/10.1101/2020.04.20.20061861 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 22, 2020. . https://doi.org/10.1101/2020.04.20.20061861 doi: medRxiv preprint

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

COVID-19: consider cytokine storm syndromes and immunosuppression

Current concepts in the diagnosis and management of cytokine release syndrome

The Propensity Score

Clinical and virological data of the first cases of COVID-19 in Europe: a case series

Effective treatment of severe COVID-19 patients

strategies including high-dose corticosteroids, IL-1 blockade or JAK inhibition also deserve to be investigated.. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 22, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 22, 2020. . https://doi.org/10.1101/2020.04.20.20061861 doi: medRxiv preprint