Acute-phase reactants during tocilizumab therapy for severe COVID-19 pneumonia.

Cassone, Giulia; Dolci, Giovanni; Besutti, Giulia; Muratore, Francesco; Bajocchi, Gianluigi; Mancuso, Pamela; Catanoso, Mariagrazia; Spaggiari, Lucia; Galli, Elena; Palermo, Adalgisa; Pipitone, Nicolò; Croci, Stefania; Massari, Marco; Facciolongo, Nicola; Menzella, Francesco; Negri, Emanuele Alberto; Zerbini, Alessandro; Belloni, Lucia; Cimino, Luca; Teopompi, Elisabetta; Sampaolesi, Fabio; Salsi, Pierpaolo; Costantini, Massimo; Giorgi Rossi, Paolo; Aldigeri, Raffaella; Salvarani, Carlo

OBJECTIVES To identify predictors of clinical improvement and intubation/death in tocilizumab-treated severe COVID19, focusing on IL6 and CRP longitudinal monitoring. METHODS 173 consecutive patients with severe COVID-19 pneumonia receiving tocilizumab in Reggio Emilia province Hospitals between 11 March and 3 June 2020 were enrolled in a prospective cohort study. Clinical improvement was defined as status improvement on a six-category ordinal scale or discharge from the hospital, whichever came first. A composite outcome of intubation/death was also evaluated. CRP and IL-6 levels were determined before TCZ administration (T0) and after 3 (T3), and 7 (T7) days. RESULTS At multivariate analysis T0 and T3 CRP levels were negatively associated with clinical improvement (OR 0.13, CI 0.03-0.55 and OR 0.11, CI 0.0-0.46) (p=0.006 and p=0.003) and positively associated with intubation/death (OR 17.66, CI 2.47-126.14 and OR 5.34, CI: 1.49-19.12) (p=0.01 and p=0.004). No significant associations with IL-6 values were observed. General linear model analyses for repeated measures showed significantly different trends for CRP from day 3 to day 7 between patients who improved and those who did not, and between patients who were intubated or died and those who were not (p<0.0001 for both). ROC analysis identified a baseline CRP level of 15.8 mg/dl as the best cut-off to predict intubation/death (AUC = 0.711, sensitivity = 0.67, specificity = 0.71). CONCLUSIONS CRP serial measurements in the first week of TCZ therapy are useful in identifying patients developing poor outcomes.