Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial

PLoS Med. 2021 Mar 3;18(3):e1003415. doi: 10.1371/journal.pmed.1003415. eCollection 2021 Mar.


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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • COVID-19 / complications
  • COVID-19 / mortality
  • COVID-19 / pathology
  • COVID-19 / therapy*
  • Chile
  • Disease Progression
  • Early Medical Intervention / methods*
  • Early Medical Intervention / statistics & numerical data
  • Female
  • Hospital Mortality
  • Humans
  • Immunization, Passive / methods
  • Immunization, Passive / mortality
  • Length of Stay / statistics & numerical data
  • Male
  • Middle Aged
  • Mortality
  • Respiration, Artificial / mortality
  • Respiration, Artificial / statistics & numerical data
  • Time-to-Treatment* / standards
  • Treatment Outcome

Supplementary concepts

  • COVID-19 serotherapy

Associated data

  • ClinicalTrials.gov/NCT04375098

Grant support

This work was supported by a grant from the Fondo de Adopción Tecnológica SiEmpre, SOFOFA Hub (https://web.sofofa.cl/centros-sofofa/sofofa-hub/), and Ministerio de Ciencia, Tecnología, Conocimiento e Innovación, Chile (https://www.minciencia.gob.cl/)(M.E.B) as well as a donation from ENEL Chile S.A. (www.enel.cl/es/sostenibilidad.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.