Tags

Type your tag names separated by a space and hit enter

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.
Autoimmun Rev. 2020 Jul; 19(7):102568.AR

Abstract

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.

Authors+Show Affiliations

Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.Pediatric Rheumatology, Children's Hospital, ASST Spedali Civili, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.Department of Laboratory Diagnostics, ASST Spedali Civili, Brescia, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.Division of Anesthesiology and Critical Care Medicine, Montichiari Hospital, ASST Spedali Civili, Brescia, Italy.Division of Pneumology, ASST Spedali Civili, Brescia, Italy.Division of Endoscopic Pneumology, ASST Spedali Civili, Brescia, Italy.Division of Nephrology and Dialysis, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; University Division of Internal Medicine and Endocrinology, ASST Spedali Civili, Brescia, Italy.Division of Cardio-Thoracic Intensive Care, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.Division of Gastroenterology, ASST Spedali Civili, Brescia, Italy.Division of Internal Medicine, Gardone Val Trompia Hospital, ASST Spedali Civili, Brescia, Italy.University Division of Internal Medicine and Endocrinology, ASST Spedali Civili, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy.Division of Anesthesiology and Critical Care Medicine, Gardone Val Trompia Hospital, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.Division of Nephrology and Dialysis, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.Pulmonary Division, Department of Medicine, Intermountain Medical Center, Murray, UT, USA.University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy.Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy; University Division of Diagnostic Radiology, ASST Spedali Civili, Brescia, Italy.Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy; Division of Cardiology, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.Division of Pneumology, ASST Spedali Civili, Brescia, Italy.University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.Third Division of Internal Medicine, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Division of Internal Medicine, ASST Spedali Civili, Brescia, Italy.University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy.Division of Gastroenterology, ASST Spedali Civili, Brescia, Italy.University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.University Division of Internal Medicine and Endocrinology, ASST Spedali Civili, Brescia, Italy.Division of Gastroenterology, ASST Spedali Civili, Brescia, Italy.Division of Internal Medicine, Gardone Val Trompia Hospital, ASST Spedali Civili, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Division of Gastroenterology, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; University Division of Internal Medicine, Montichiari Hospital, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; University Division of Geriatric Internal Medicine, Montichiari Hospital, ASST Spedali Civili, Brescia, Italy.Third Division of Internal Medicine, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Division of Internal Medicine, ASST Spedali Civili, Brescia, Italy.Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy; Division of Nephrology and Dialysis, ASST Spedali Civili, Brescia, Italy.University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.First Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy.University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.Division of Pneumology, ASST Spedali Civili, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.First Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy.Pediatric Rheumatology, Children's Hospital, ASST Spedali Civili, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; University Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy.Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.University Division of Anesthesiology and Critical Care Medicine, ASST Spedali Civili, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. Electronic address: nicola.latronico@unibs.it.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32376398

Citation

Toniati, Paola, et al. "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." Autoimmunity Reviews, vol. 19, no. 7, 2020, p. 102568.
Toniati P, Piva S, Cattalini M, et al. 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. Autoimmun Rev. 2020;19(7):102568.
Toniati, P., Piva, S., Cattalini, M., Garrafa, E., Regola, F., Castelli, F., Franceschini, F., Airò, P., Bazzani, C., Beindorf, E. A., Berlendis, M., Bezzi, M., Bossini, N., Castellano, M., Cattaneo, S., Cavazzana, I., Contessi, G. B., Crippa, M., Delbarba, A., ... Latronico, N. (2020). 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. Autoimmunity Reviews, 19(7), 102568. https://doi.org/10.1016/j.autrev.2020.102568
Toniati P, et al. 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. Autoimmun Rev. 2020;19(7):102568. PubMed PMID: 32376398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Toniati,Paola, AU - Piva,Simone, AU - Cattalini,Marco, AU - Garrafa,Emirena, AU - Regola,Francesca, AU - Castelli,Francesco, AU - Franceschini,Franco, AU - Airò,Paolo, AU - Bazzani,Chiara, AU - Beindorf,Eva-Andrea, AU - Berlendis,Marialma, AU - Bezzi,Michela, AU - Bossini,Nicola, AU - Castellano,Maurizio, AU - Cattaneo,Sergio, AU - Cavazzana,Ilaria, AU - Contessi,Giovanni-Battista, AU - Crippa,Massimo, AU - Delbarba,Andrea, AU - De Peri,Elena, AU - Faletti,Angela, AU - Filippini,Matteo, AU - Filippini,Matteo, AU - Frassi,Micol, AU - Gaggiotti,Mario, AU - Gorla,Roberto, AU - Lanspa,Michael, AU - Lorenzotti,Silvia, AU - Marino,Rosa, AU - Maroldi,Roberto, AU - Metra,Marco, AU - Matteelli,Alberto, AU - Modina,Denise, AU - Moioli,Giovanni, AU - Montani,Giovanni, AU - Muiesan,Maria-Lorenza, AU - Odolini,Silvia, AU - Peli,Elena, AU - Pesenti,Silvia, AU - Pezzoli,Maria-Chiara, AU - Pirola,Ilenia, AU - Pozzi,Alessandro, AU - Proto,Alessandro, AU - Rasulo,Francesco-Antonio, AU - Renisi,Giulia, AU - Ricci,Chiara, AU - Rizzoni,Damiano, AU - Romanelli,Giuseppe, AU - Rossi,Mara, AU - Salvetti,Massimo, AU - Scolari,Francesco, AU - Signorini,Liana, AU - Taglietti,Marco, AU - Tomasoni,Gabriele, AU - Tomasoni,Lina-Rachele, AU - Turla,Fabio, AU - Valsecchi,Alberto, AU - Zani,Davide, AU - Zuccalà,Francesco, AU - Zunica,Fiammetta, AU - Focà,Emanuele, AU - Andreoli,Laura, AU - Latronico,Nicola, Y1 - 2020/05/03/ PY - 2020/04/16/received PY - 2020/04/17/accepted PY - 2020/5/8/pubmed PY - 2020/6/11/medline PY - 2020/5/8/entrez SP - 102568 EP - 102568 JF - Autoimmunity reviews JO - Autoimmun Rev VL - 19 IS - 7 N2 - 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. SN - 1873-0183 UR - https://www.unboundmedicine.com/medline/citation/32376398/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1568-9972(20)30130-0 DB - PRIME DP - Unbound Medicine ER -