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

Toniati, Paola; Piva, Simone; Cattalini, Marco; Garrafa, Emirena; Regola, Francesca; Castelli, Francesco; Franceschini, Franco; Airò, Paolo; Bazzani, Chiara; Beindorf, Eva-Andrea; Berlendis, Marialma; Bezzi, Michela; Bossini, Nicola; Castellano, Maurizio; Cattaneo, Sergio; Cavazzana, Ilaria; Contessi, Giovanni-Battista; Crippa, Massimo; Delbarba, Andrea; De Peri, Elena; Faletti, Angela; Filippini, Matteo; Filippini, Matteo; Frassi, Micol; Gaggiotti, Mario; Gorla, Roberto; Lanspa, Michael; Lorenzotti, Silvia; Marino, Rosa; Maroldi, Roberto; Metra, Marco; Matteelli, Alberto; Modina, Denise; Moioli, Giovanni; Montani, Giovanni; Muiesan, Maria-Lorenza; Odolini, Silvia; Peli, Elena; Pesenti, Silvia; Pezzoli, Maria-Chiara; Pirola, Ilenia; Pozzi, Alessandro; Proto, Alessandro; Rasulo, Francesco-Antonio; Renisi, Giulia; Ricci, Chiara; Rizzoni, Damiano; Romanelli, Giuseppe; Rossi, Mara; Salvetti, Massimo; Scolari, Francesco; Signorini, Liana; Taglietti, Marco; Tomasoni, Gabriele; Tomasoni, Lina-Rachele; Turla, Fabio; Valsecchi, Alberto; Zani, Davide; Zuccalà , Francesco; Zunica, Fiammetta; Focà , Emanuele; Andreoli, Laura; Latronico, Nicola

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.