Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia.

BACKGROUND: IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. OBJECTIVE: Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score-adjusted Cox model. RESULTS: A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70). CONCLUSIONS: This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.

Multidimensional prognostic index (MPI) predicts non-invasive ventilation failure in older adults with acute respiratory failure.

BACKGROUND: Acute respiratory failure (ARF) is a very common complication among hospitalized older adults. Non-invasive ventilation (NIV) may avoid admission to intensive care units, intubation and their related complication, but still lacks specific indications in older adults. Multidimensional Prognostic Index (MPI) based on comprehensive geriatric assessment (CGA) could have a role in defining the short-term prognosis and the best candidates for NIV among older adults with ARF. METHODS: This is a retrospective observational study which enrolled patients older than 70 years, consecutively admitted to an acute geriatric unit with ARF. A standardized CGA was used to calculate the MPI at admission. Multivariate Cox regression models were used to test if MPI score could predict in-hospital mortality and NIV failure. Receiver operator curve (ROC) analysis was used to identify the discriminatory power of MPI for NIV failure. RESULTS: We enrolled 231 patients (88.2 ± 5.9 years, 47% females). Mean MPI at admission was 0.76±0.16. In-hospital mortality rate was 33.8%, with similar incidence in patients treated with and without NIV. Among NIV users (26.4%), NIV failure occurred in 39.3%. Higher MPI scores at admission significantly predicted in-hospital mortality (ß=4.46, p<0.0001) among patients with ARF and NIV failure (ß=7.82, p = 0.001) among NIV users. MPI showed good discriminatory power for NIV failure (area under the curve: 0.72, 95% CI: 0.58-0.85, p<0.001) with optimal cut-off at MPI value of 0.84. CONCLUSIONS: MPI at admission might be a useful tool to early detect patients more at risk of in-hospital death and NIV failure among older adults with ARF.