Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

Early Treatment with Bamlanivimab Alone does not Prevent COVID-19 Hospitalization and Its Post-Acute Sequelae. A Real Experience in Umbria, Italy.

BACKGROUND AND OBJECTIVE: The use of monoclonal antibodies to the SARS-Cov-2 spike protein for early treatment of COVID-19 disease is being evaluated, with only phase 2 studies available to date. The emergency authorization of bamlanivimab monotherapy was obtained in November 2020 by the FDA and in March 2021 by Italian agency AIFA. Its use was then revoked in April 2021 by both. This study reports the results of bamlanivimab utilization in monotherapy in Umbria (Italian region) to verify whether, in a population with multiple risk factors, comparable results to the phase 2 BLAZE1 trial had been obtained. METHODS: Between March and April 2021, a retrospective observational study was performed on patients treated with bamlanivimab. Demographic and clinical characteristics before and after infusion were evaluated. Moreover, a telephone interview was conducted about 30 days after the infusion to evaluate the overall course. RESULTS: All patients had an early infection (mean 4±1.73 days), almost all by alpha variant (97%). No adverse events to treatment were observed. Altogether within 30 days, the hospitalization rate was 20%, 15% for COVID-19 related pathologies, versus 4% at 11 days in the BLAZE1 phase 2 study. In addition, worsening of some symptoms observed at baseline such as asthenia (77 vs. 51.3%), shortness of breath (38 vs. 23%) was registered, as well as the onset of non-restorative sleep (41%). CONCLUSION: The clinical outcome after bamlanivimab monotherapy was far below the expectation despite the patients had been infected by a theoretically sensitive viral variant.