Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:147

Article

Bozzi, Giorgio¹  Mangioni, Davide^1,2  Minoia, Francesca³  Aliberti, Stefano^4,5,6  Grasselli, Giacomo^6,7  Barbetta, Laura⁸  Castelli, Valeria¹  Palomba, Emanuele¹  Alagna, Laura¹  Lombardi, Andrea¹  Ungaro, Riccardo¹  Agostoni, Carlo^3,9  Baldini, Marina¹⁰  Blasi, Francesco^4,5,6  Cesari, Matteo^9,11  Costantino, Giorgio^7,9  Fracanzani, Anna Ludovica^6,12  Montano, Nicola^6,13  Monzani, Valter⁸  Pesenti, Antonio^6,7  Peyvandi, Flora^6,14  Sottocorno, Marcello¹⁵  Muscatello, Antonio¹  Filocamo, Giovanni³  Gori, Andrea^1,6,16  Bandera, Alessandra^1,6,16 

[1] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Infect Dis Unit, Milan, Italy

[2] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy

[3] Fdn IRCCS Ca Granda Osped Maggiore Policlin, UOC Pediat Media Intensita Cure, Milan, Italy

[4] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Resp Unit, Milan, Italy

[5] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Cyst Fibrosis Adult Ctr, Milan, Italy

[6] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy

[7] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Anesthesia Crit Care & Emergency, Milan, Italy

[8] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Acute Med Unit, Milan, Italy

[9] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy

[10] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Internal Med Unit, Milan, Italy

[11] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Geriatr Unit, Milan, Italy

[12] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Internal Med & Metab Dis Unit, Milan, Italy

[13] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Internal Med Unit, Immunol & Allergol Unit, Milan, Italy

[14] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Internal Med & Hemostasis & Thrombosis Unit, Milan, Italy

[15] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Hosp Pharm, Milan, Italy

[16] Univ Milan, Ctr Multidisciplinary Res Hlth Sci, Milan, Italy

关键词: SARS-CoV-2;    COVID-19;    hyperinflammation;    anti-IL-1;    anakinra;    corticosteroids;    methylprednisolone;    immunomodulation;    respiratory failure;    mechanical ventilation;   

DOI  :  10.1016/j.jaci.2020.11.006

来源: Elsevier

【 摘 要 】

Background: Immunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2-induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19). Objective: We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Methods: A secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020) with hyperinflammation (ferritin >1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO(2) Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO2:FiO2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model). Results: A total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO2:FiO(2) ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P 5.005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P 5.007, and HR, 0.18, 95% CI, 0.07-0.50, P 5.001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered. Conclusions: Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results.

【 授权许可】

Free