부산대학교 도서관

Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods and findings: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32–2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54–17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54–17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19–2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. Conclusions: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. Trial registration: NCT04375098. In this randomized trial, María Elvira Balcells and colleagues demonstrate that there is no benefit in immediate versus delayed convalescent plasma administration for COVID-19 patients. Author summary: Why was this study done?: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a matter of worldwide concern, and except for corticosteroids, no other validated treatment against SARS-CoV-2 has been found so far. Plasma from convalescent patients containing antibodies against the virus is being widely used as a treatment alternative against this virus, but few randomized clinical trials have been carried out to show any clinical benefit for patients with COVID-19. What did the researchers do and find?: We conducted a randomized clinical trial. Fifty-eight hospitalized patients in the early stages of COVID-19 (≤7 days of symptoms) and with a high risk of progression into respiratory failure were recruited. Patients were randomized into 2 groups: The early plasma group received convalescent plasma at enrollment, and the deferred plasma group received convalescent plasma only in case of respiratory aggravation or if the patient still required hospitalization for symptomatic COVID-19 >7 days after enrollment. The proportion achieving the combined primary outcome of mechanical ventilation, prolonged hospitalization, or in-hospital death was 32.1% with immediate plasma versus 33.3% in the arm deferring plasma until aggravation, a non-significant difference. What do these findings mean?: Our study failed to show that early convalescent plasma administration improves the outcome compared to convalescent plasma use only in case of clinical deterioration. The small sample size of the study precludes any definitive conclusions, but the results are in agreement with observations from other trials on convalescent plasma for patients hospitalized with COVID-19. [ABSTRACT FROM AUTHOR]