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.

Apneic Tracheostomy in COVID-19 Patients on Veno-Venous Extracorporeal Membrane Oxygenation.

COVID-19 creates an impressive burden for intensive care units in terms of need for advanced respiratory care, with a huge number of acute respiratory distress syndromes (ARDS) requiring prolonged mechanical ventilation. In some cases, this proves to be insufficient, with a refractory respiratory failure calling for an extracorporeal approach (veno-venous ECMO). In this scenario, most of these patients need an early tracheostomy procedure to be carried out, which creates the risk of distribution of aerosol particles, possibly leading to personnel infection. The use of apneic tracheostomy has been proposed for COVID-19 patients, but in case of ECMO it may produce lung derecruitment, severe hypoxemia, and sudden worsening of respiratory mechanics. We developed an apneic tracheostomy technique and applied it in over 32 patients supported by veno-venous ECMO. We present data showing the safety and feasibility of this technique in terms of patient care and personnel protection. Gas exchange and pH did not show statistically significant changes after the tracheostomy, nor did respiratory mechanics data or the need for inspiratory pressure and FiO2. The use of apneic tracheostomy was a safe option for patient care during ECMO and reduced the possibility of virus spreading.