A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia

Original: NEJM November 24, 2020

Author(s): Simonovich VA, Burgos Pratx LD, Scibona P et al

Respiratory digests
Respiratory infections
A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia - article image

Reviewer: Stylianos Loukides, e-Learning Director

Published: 01 Dec, 2020

COVID-19 infenction is still lacking effective and ideal treatment. In the current study, the authors randomly assigned hospitalized adult patients with severe Covid-19 pneumonia to receive either convalescent plasma or placebo. The ratiio of assignment was 2:1. The primary outcome was the patient’s clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. Analyzing the above six-point ordinal scale we can notice a wide range of outcomes like, death, mechanical ventilation, oxygen requirement, no supplemental oxygen requirement, discharged without full return to baseline physical function, and finally discharged with full return to baseline physical function.

228 patients were randomized to receive convalescent plasma and 105 to receive placebo. Patients were eligible to participate if they had a positive RT-PCR for SARS-COV 2, radiologically confirmed pneumonia and no previous directives rejecting advanced life support and one of the followwing parameters: Saturation at rest below 93%, PaO2:FiO2 <300mmHg, or a Sequential Organ Failure Assessment (SOFA) or modified SOFA (mSOFA) score of two or more points above baseline status (scores range from 0 to 24, with higher scores indicating more severe disease). Eligible donors for convalescent plasma were those with a minimum SARS-CoV-2 total antibody titer of 1:400.
However the median plasma titer was 1:3200 ranging from 1:800 to 1:3200.

Patients were enrolled approximately 8 days from the onset of symptoms. Hypoxemia was the predominant criterion for the above enrollment.

The results showed that no statistical significant difference was observed in terms of mortality. 10.96% in the convalescent plasma group and 11.43% in the placebo group.
Furthermore, no significant difference was observed between the convalescent plasma group and the placebo group in terms of different clinical outcomes in ordinal based scale. Similar results were observed for ICU admissions and the need of mechanical ventilation. Hospitalization days were similar between the two groups. Considering subgroup analyses, no driven characteristics were noticed. Finally safety issues were not remarkable.

The authors finally concluded that the use of convalescent plasma did not result in a significant clinical benefit as compared with placebo in patients with severe Covid-19 pneumonia.

###Comment:
Another negative trial for COVID-19 related pneumonia. There are three main issues that need further assessment:

  • The early treatment approach, meaning receiving plasma at the onset of symptoms and not waiting for 7-10 days.
  • Avoid other interventions which may alter the immunosuppresive status.
  • Administer a lower titer of antibodies.