Cristina Mussini1,2, Alessandro Cozzi-Lepri3, Marianna Menozzi1, Marianna Meschiari1, Erica Franceschini1, Jovana Milic2, Lucio Brugioni4, Antonello Pietrangelo5, Massimo Girardis2,6, Andrea Cossarizza5, Roberto Tonelli7, Enrico Clini5,7, Marco Massari8, Michele Bartoletti9, Anna Ferrari10, Anna Maria Cattelan10, Paola Zuccalà11, Miriam Lichtner11, Roberto Rossotti12, Enrico Girardi13, Emanuele Nicastri13, Massimo Puoti13,14, Andrea Antinori13, Pierluigi Viale9, Giovanni Guaraldi1,2. 1. Department of Infectious Diseases, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy. 2. Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy. 3. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL Population Health Sciences, University College London, London, United Kingdom. 4. Internal Medicine Department, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy. 5. Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy. 6. Department of Anaesthesia and Intensive Care Unit, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy. 7. Respiratory Diseases Unit, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy. 8. Infectious Disease Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. 9. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 10. Infectious Disease Unit, Azienda Ospedale, University of Padua, Padua, Italy. 11. Department of Public Health and Infectious Disease, Sapienza University of Rome, Polo Pontino, Italy. 12. Niguarda Hospital Milan, Milano, Italy. 13. National Institute for Infectious Diseases L. Spallanzani (INMI), Rome, Italy. 14. School of Medicine, Università degli studi di Milano Bicocca, Milano, Italy.
Abstract
BACKGROUND: The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients' profile. METHODS: Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort. RESULTS: 266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively. CONCLUSIONS: Our score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies.
BACKGROUND: The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients' profile. METHODS:Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort. RESULTS: 266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively. CONCLUSIONS: Our score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies.
Authors: Carlos Salama; Jian Han; Linda Yau; William G Reiss; Benjamin Kramer; Jeffrey D Neidhart; Gerard J Criner; Emma Kaplan-Lewis; Rachel Baden; Lavannya Pandit; Miriam L Cameron; Julia Garcia-Diaz; Victoria Chávez; Martha Mekebeb-Reuter; Ferdinando Lima de Menezes; Reena Shah; Maria F González-Lara; Beverly Assman; Jamie Freedman; Shalini V Mohan Journal: N Engl J Med Date: 2020-12-17 Impact factor: 91.245
Authors: Peter Horby; Wei Shen Lim; Jonathan R Emberson; Marion Mafham; Jennifer L Bell; Louise Linsell; Natalie Staplin; Christopher Brightling; Andrew Ustianowski; Einas Elmahi; Benjamin Prudon; Christopher Green; Timothy Felton; David Chadwick; Kanchan Rege; Christopher Fegan; Lucy C Chappell; Saul N Faust; Thomas Jaki; Katie Jeffery; Alan Montgomery; Kathryn Rowan; Edmund Juszczak; J Kenneth Baillie; Richard Haynes; Martin J Landray Journal: N Engl J Med Date: 2020-07-17 Impact factor: 91.245
Authors: Noa Biran; Andrew Ip; Jaeil Ahn; Ronaldo C Go; Shuqi Wang; Shivam Mathura; Brittany A Sinclaire; Urszula Bednarz; Michael Marafelias; Eric Hansen; David S Siegel; Andre H Goy; Andrew L Pecora; Ihor S Sawczuk; Lauren S Koniaris; Micky Simwenyi; Daniel W Varga; Lisa K Tank; Aaron A Stein; Valerie Allusson; George S Lin; William F Oser; Roman A Tuma; Joseph Reichman; Louis Brusco; Kim L Carpenter; Eric J Costanzo; Vincent Vivona; Stuart L Goldberg Journal: Lancet Rheumatol Date: 2020-08-14