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Background The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. Methods In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04351152 , and is completed. Findings Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41–137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79–89) participants in the lenzilumab group and in 190 (78%; 72–83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. Interpretation Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with CO...

RATIONALE: Penicillin is reported as a drug allergy in 10% of the general population. We studied the epidemiology of documented penicillin allergy in patients entering the ED of an inner-city tertiary care hospital including the general prevalence, prevalence by race, and reports of multiple drug allergies, defined as 2 or more allergies. METHODS: This was a retrospective review of patients entering the ED of University Hospital from 01/2017-07/2017. We identified all patients with a documented penicillin allergy by a query of the electronic medical record, removing duplicate presentations for the same patient. The total number of patients presenting to the ED over the same time frame was identified. Excel sheet filters were used to tally the number of patients with penicillin allergy, the number of African Americans and Whites with penicillin allergy, and the number of patients with multiple drug allergies. RESULTS: Of 7291 patients presenting the ED from 01/2017 to 07/2017, 2503 (34%) had documented penicillin allergy. Penicillin allergy was documented in 45% (1390/3043) of African American patients. Similarly 46% (385/832) of White patients had documented penicillin allergy. Twenty-eight percent (701/2503) of patients with penicillin allergy also reported allergy to multiple drugs. CONCLUSIONS: The prevalence of documented penicillin allergy is greater in our inner-city tertiary care hospital than in the general population (34% versus 10%). Prevalence in the African American and White population is approximately equal, but greater than the general population. Patients with penicillin allergy are likely to report allergies to two or more drugs.

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