JOURNAL ARTICLE
REVIEW

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy

Paola Toniati, Simone Piva, Marco Cattalini, Emirena Garrafa, Francesca Regola, Francesco Castelli, Franco Franceschini, Paolo Airò, Chiara Bazzani, Eva-Andrea Beindorf, Marialma Berlendis, Michela Bezzi, Nicola Bossini, Maurizio Castellano, Sergio Cattaneo, Ilaria Cavazzana, Giovanni-Battista Contessi, Massimo Crippa, Andrea Delbarba, Elena De Peri, Angela Faletti, Matteo Filippini, Matteo Filippini, Micol Frassi, Mario Gaggiotti, Roberto Gorla, Michael Lanspa, Silvia Lorenzotti, Rosa Marino, Roberto Maroldi, Marco Metra, Alberto Matteelli, Denise Modina, Giovanni Moioli, Giovanni Montani, Maria-Lorenza Muiesan, Silvia Odolini, Elena Peli, Silvia Pesenti, Maria-Chiara Pezzoli, Ilenia Pirola, Alessandro Pozzi, Alessandro Proto, Francesco-Antonio Rasulo, Giulia Renisi, Chiara Ricci, Damiano Rizzoni, Giuseppe Romanelli, Mara Rossi, Massimo Salvetti, Francesco Scolari, Liana Signorini, Marco Taglietti, Gabriele Tomasoni, Lina-Rachele Tomasoni, Fabio Turla, Alberto Valsecchi, Davide Zani, Francesco Zuccalà, Fiammetta Zunica, Emanuele Focà, Laura Andreoli, Nicola Latronico
Autoimmunity Reviews 2020, 19 (7): 102568
32376398
A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

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