Giulia Cassone1, Giovanni Dolci2, Giulia Besutti3, Francesco Muratore4, Gianluigi Bajocchi4, Pamela Mancuso5, Mariagrazia Catanoso4, Lucia Spaggiari6, Elena Galli7, Adalgisa Palermo7, Nicolò Pipitone4, Stefania Croci8, Marco Massari9, Nicola Facciolongo10, Francesco Menzella10, Emanuele Alberto Negri11, Alessandro Zerbini8, Lucia Belloni8, Luca Cimino12, Elisabetta Teopompi13, Fabio Sampaolesi9, Pierpaolo Salsi14, Massimo Costantini15, Paolo Giorgi Rossi5, Raffaella Aldigeri16, Carlo Salvarani17. 1. University of Modena and Reggio Emilia, Modena; Clinical and Experimental Medicine PhD program, University of Modena and Reggio Emilia, Modena; and Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 2. University of Modena and Reggio Emilia, Modena, and Infectious Disease Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 3. University of Modena and Reggio Emilia, Modena; Clinical and Experimental Medicine PhD program, University of Modena and Reggio Emilia, Modena; and Radiology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 4. Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 5. Epidemiology Service, Azienda USL-IRCCS di Reggio Emilia, Italy. 6. Radiology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 7. University of Modena and Reggio Emilia, Modena, Italy. 8. Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 9. Infectious Disease Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 10. Pneumology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 11. High Intensity Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 12. Immuno-Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 13. Internal Medicine Unit, Guastalla Hospital, Azienda USL-IRCCS di Reggio Emilia, Italy. 14. Intensive Care Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. 15. Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, Italy. 16. Department of Medicine and Surgery, University of Parma, Italy. 17. University of Modena and Reggio Emilia, Modena, and Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy. salvarani.carlo@ausl.re.it.
Abstract
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.
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.