key: cord-0965137-l8ee3t4w
authors: Lucio Liberato, Nicola; De Monte, Andrea; Caravella, Giuseppe
title: Tocilizumab in severe COVID-19
date: 2020-07-16
journal: Arch Med Sci
DOI: 10.5114/aoms.2020.97411
sha: 871f8a6fa1307cb4e6da6e34d2b53cf805c12843
doc_id: 965137
cord_uid: l8ee3t4w

nan

Nicola Lucio Liberato 1 , Andrea De Monte 2 , Giuseppe Caravella 3 Clinical and biological data suggest that the occurrence of a cytokine storm may be crucial in determining the clinical features and severity of COVID-19, with interleukin-6 playing a major role; thus, inhibiting its activity by blocking its binding to the specific receptor could be useful [1] .

Here we report on the use of tocilizumab (RoActemra © , Roche), a humanised anti-human interleukine-6 receptor antibody, in 20 hospitalised patients with SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction assay and severe pneumonia (PaO 2 /FiO 2 ratio < 300) undergoing high flow oxygen or noninvasive positive-pressure ventilation with interleukin-6 serum levels higher than 20 pg/ml; mechanically ventilated patients were excluded. In these patients, tocilizumab 8 mg/kg intravenously (maximum 800 mg) were added to standard treatment (hydroxychloroquine, prophylactic enoxaparin, oxygen, and nutritional support); a further identical dose was administered 12 h later if no significant amelioration could be found. The drug was prescribed as off-label, and local Ethics Committee approval and informed consent were obtained for each patient. Patients were followed until discharge or death; 1 patient is still hospitalised.

The age range was 32 to 78 years (median 60 years) (Table I) . At baseline, 18 patients were receiving noninvasive positive-pressure ventilation, and 2 patients recieved high-flow oxygen; median PaO 2 /FiO 2 ratio was 137 (range: 101-210). The median duration of symptoms before tocilizumab therapy was 10.5 days (range: 3-21 days), and tocilizumab was administered a median of 2.5 days after admission (range: 0-13). Four patients underwent mechanical ventilation during follow-up: 1 patient died, 2 patients were extubated and discharged, and 1 patient was extubated but still in intensive care due to intervening septic complications. The time to cessation of high-flow oxygen or noninvasive positive-pressure ventilation was 5.5 days, and the median duration of hospitalisation was 15 days (range: 7-52 days). The mortality rate was 5%, and there were no clinical and laboratory differences between patients who required or did not require mechanical ventilation during hospitalisation. No adverse drug reaction was reported.

It is still a matter of debate whether the clinical course of COVID-19 is different in patients with rheumatic disease or in those undergoing a disease-modifying treatment [2, 3] . A previous report from China showed that tocilizumab could be an effective treatment, able to reduce the mortality of COVID-19 patients [4] . Data from our preliminary report Creative Commons licenses: This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY -NC -SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/). seems to confirm such an effect and compare well with those from other studies: the mortality rate was 14% in severe Chinese patients [5] , 22% in patients treated with lopinavir-ritonavir [6] , and 13% in patients treated with remdesivir [7] , while the aggregated data of death and intubation was 20% (4 patients) in our series, and 32.3% in patients treated with hydroxychloroquine alone [8] . Adding Tocilizumab to standard treatment in patients with severe COVID-19 could therefore be useful.

Our study has significant shortcomings: mainly the small size of the treated cohort and the lack of a control (possibly randomised) group, which limit the interpretation of the results.

These preliminary data therefore need confirmation in larger populations by case-control studies and mainly by randomised studies.

Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?

Susceptibility and severity of COVID-19 in patients treated with bDMARDS and tsDMARDs: a population-based study

Clinical characteristics and outcomes of patients with Coronavirus Disease 2019 (COVID-19) and rheumatic disease: a comparative cohort study from a US "Hoit Spot

Effective treatment of severe COVID-19 patients with tocilizumab

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention

A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19

Compassionate use of remdesivir for patients with severe Covid-19

Observational study of hydroxychloroquine in hospitalized patients with Covid-19

Hospitalisation, median (IQR)

The authors declare no conflict of interest.R e f e r e n c e s