Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease
Manaf Alqahtani, Abdulkarim Abdulrahman, Abdulrahman Almadani, Salman Yousif Alali, Alaa Mahmood Al Zamrooni, Amal Hamza Hejab, Ronán M Conroy, Pearl Wasif, Sameer Otoom, Stephen L Atkin, Manal Abduljalil
Scientific Reports, doi:10.1038/s41598-021-89444-5
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.
Coronavirus disease 2019 (COVID-19 ) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic with serious global public health and economic sequelae. As of 25 February 2021, more than 113 million cases have been confirmed worldwide leading to over 2.5 million deaths 1 . There have been a number of reports of medications, such as remdesivir, with antiviral properties that have shown efficacy against SARS-CoV-2 with shorter time to recovery 2 . Whilst there are now several effective vaccines emerging and being used globally, the rate of COVID-19 disease and its complications currently remain high. 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 disease 3 . This has been shown to be effective in severe acute respiratory syndrome 4 , Ebola virus infection 5 and in H1N1 influenza 6 . More recently, there has been a report of the use of CP in the treatment of five mechanically ventilated COVID-19 patients with the suggestion of expedited recovery as the patients improved one week after the transfusion 7 . A randomized trial with CP therapy in severely and critically ill COVID-19 patients undertaken in China was stopped early as recruitment slowed down due to the decrease in COVID-19 cases in China 8 . Similarly, an open label randomized trial in the Netherlands was stopped prematurely due to the detection of baseline neutralizing..
Author contributions A.A., A.A. and S.L.A. analyzed the data and wrote the manuscript. S.Y.A., A.Z., A.H., P.W. and M.A. performed data collection, S.O. interpreted data and edited the manuscript. R.C. performed the statistical analysis. M.A.Q. supervised data collection, data analysis and edited the manuscript. All authors reviewed and approved the final version of the manuscript. M.A. is the guarantor of this work.
Competing interests The authors declare no competing interests.
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'abstract': '<jats:title>Abstract</jats:title><jats:p>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\xa0ml 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\xa0days. The CP group were a higher risk group with higher '
'ferritin levels (<jats:italic>p</jats:italic>\u2009<\u20090.05) 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, <jats:italic>p</jats:italic>\u2009=\u20090.72); 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.</jats:p><jats:p><jats:italic>Clinical trials registration</jats:italic> NCT04356534: '
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'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': 'The authors declare no competing interests.',
'order': 1,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}],
'article-number': '9927'}
