The RECOVERY trial

An interesting article published in The Lancet by the recovery collaborative group dated May 14Th 2021, sought to answer this question. 

Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies.  

This trial aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.

The trial was assessing several possible treatments in patients hospitalised with COVID-19 in the United Kingdom.

The trial is currently underway at 177 NHS hospitals from across the UK.

Eligible and consenting patients were randomly assigned to receive either usual care alone or usual care plus high titre convalescent plasma.  

The primary outcome was assessed with 28-day mortality.  

Between May 28th 2020 and January 15th 2021, 16,287 patients were enrolled in the recovery trial and 11,558 were eligible to receive convalescent plasma and these were assigned to either the convalescent plasma group or the usual care group.

There were no significant difference in 28-day mortality between the two groups.

1,399 patients that is 24% of the 5,795 patients in the convalescent plasma group and 1408 patients, that is 24% of the 5,763 patients in the usual care group sadly died within 28 days.

The 28-day mortality rate ratio was similar in all pre-specified subgroups of patients – including in those patients without detectable SARS-CoV-2 antibodies at randomisation. 

Allocation to the convalescent plasma group had no significant effect on the proportion of patients discharged from hospital within 28 days. 

66%, that is 3,832 patients in the convalescent plasma group versus 3,822 patients in the usual care group.  

Amongst those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite end point of progression to invasive mechanical ventilation or sadly death, 1,568 that is 29% of the 5,493 patients in the convalescent plasma group versus 1,568, 29% of 5,448 patients in the usual care group.

Unfortunately, the results of this large randomised trial study showed that convalescent plasma did not improve survival or other clinical outcomes in patients hospitalised with COVID-19.  

The results were consistent across subgroups of age, sex, ethnicity, duration of symptoms before randomisation, level of respiratory support received at randomisation and use of corticosteroids.  

This trial provides results which are consistent with evidence from previously reported randomised trials of convalescent plasma for patients hospitalised with COVID-19. 

It has been suggested that the benefits of convalescent plasma may depend on the level of transfused neutralising titres and that using plasma with lower titres could explain negative results from previous randomised trials.  

In this study, all convalescent plasma was supplied via the UK National Blood Service using standardised laboratory processing.  

Convalescent donors were chosen based on a high anti-spike IgG concentration which correlated with neutralising antibody.  

Nearly all the participants received plasma from two different donors to increase the chance at least one contained higher concentrations of neutralising antibodies.

It has also been considered whether the presence of anti-SARS-CoV-2 antibodies in recipients at the time of transfusion with the convalescent plasma has also had a possible reason for the absence of any observed effect.  

In this recovery trial 38% of patients were seronegative at randomisation, and, although they had a markedly higher 28-day mortality risk than patients who were seropositive at randomisation, they did not observe a significant survival benefit from convalescent plasma.  

It was also considered whether antibody based therapies could be more effective during the early stages of COVID-19, when viral replication dominates.  

This study did not identify a benefit of convalescent plasma when patients were stratified by time since onset of illness.  

In particular, they did not identify a mortality benefit in the subgroup of patients allocated to convalescent plasma four days or less from illness onset, which by itself compromised more patients than the total number of patients enrolled in all other convalescent plasma trials combined.  

During this pandemic caused by this new virus, convalescent plasma appears an appealing treatment because it might be available within weeks of an outbreak.  

Previous to this RECOVERY trial, there has been insufficient evidence from randomised trials to reliably assess its safety and efficacy.

Unfortunately, this trial did not find evidence that high titre convalescent plasma improved survival or other pre-specified clinical outcomes in patients hospitalised with COVID-19.  

However, whether convalescent plasma would benefit other patient groups is unknown and needs to be evaluated.  

The London General Practice, the leading London doctor’s clinic, commends all researchers on the high quality of research which has been undertaken with this new novel virus SARS-CoV-2.  

LGP undertakes all forms of COVID testing and is approved by the Government for all regulatory day two, day eight, fit to fly and day five test for release testing. 

It also provides a comprehensive service to look after any patient with COVID-19 including acute COVID, which we offer a monitoring service for, long COVID and post-acute COVID.

Dr Paul Ettlinger

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