Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

Manaf Alqahtani,Amal Hamza Hejab,Stephen L Atkin,Alaa Mahmood Al Zamrooni,Pearl Wasif,Abdulkarim Abdulrahman,Abdulrahman Almadani,Manal Abduljalil,Sameer Otoom,Ronán M Conroy,Salman Yousif Alali

doi:10.1038/s41598-021-89444-5

Abstract

Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22–2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

Highlights

Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease
The CP group appeared to have a higher systemic inflammatory response shown by the increased ferritin and D-dimer levels and more patients with chronic lung disease were included, a known risk factor for more severe d isease[14]; respiratory indices did not differ between the groups
The higher ferritin and D-dimer levels shown in the CP group have been reported to predict poorer outcomes for those patients, indicating that the CP group were at a higher baseline risk[15,16]

Summary

Introduction

Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, a larger definitive study is needed for confirmation. Plasma therapy using Convalescent Plasma (CP) transfusion refers to a form of passive therapy, where neutralizing antibodies from a recovered donor are injected into the infected patient with the aim of altering the course of the d isease[3] This has been shown to be effective in severe acute respiratory s yndrome[4], Ebola virus infection[5] and in H1N1 influenza[6]. No studies have been undertaken with CP therapy in hypoxic patients and this pilot trial was undertaken

Methods

Results

Conclusion