Treating critically ill COVID-19 patients with blood plasma from people who have fought off the disease has limited impact on patient outcomes.

The early findings, which are yet to be published, come from the REMAP-CAP study and show that treatment with convalescent plasma did not improve outcomes among patients requiring intensive care unit (ICU) support.

There was no evidence of harm associated with the administration of convalescent plasma, but investigators have paused enrollment of severely ill COVID-19 patients in ICU to this arm of REMAP-CAP study.

They explain the trial will continue to recruit hospitalised COVID-19 patients who are moderately unwell and are not requiring intensive care, to assess if less severely ill patients benefit from the treatment.

Professor Anthony Gordon, Professor of anesthesia and critical care at Imperial College London and an NIHR research professor, said: “I am glad REMAP-CAP has been able to provide important evidence about which patients might benefit from convalescent plasma.

“Although it is disappointing that all critically ill patients don’t appear to gain any benefit, this is still vitally important to know. Convalescent plasma is a precious resource, and we can now continue to focus on identifying exactly which patients might benefit the most from treatment – maybe people earlier in their illness or those with weak immune systems.”

Antibodies against the virus

Convalescent plasma – the yellowish liquid making up half of our blood volume – is obtained from people who have recovered from COVID-19 and contains antibodies against the SARS-CoV-2 virus. By administering plasma to sick patients, the hope is that these antibodies can neutralize the virus in their bodies, preventing further replication and halting ongoing tissue damage.

The latest analysis, based on 912 participants who were severely ill and had outcome data available, showed that overall convalescent plasma was unlikely to be beneficial, with a very low probability (2.2%) that it improved the chances of decreasing the number of days requiring intensive care support or death by more than 20%.

Although it is disappointing that all critically ill patients don’t appear to gain any benefit, this is still vitally important to know. Professor Anthony Gordon NIHR Professor

However, this initial analysis did not examine the effect of convalescent plasma in moderately ill patients. Whether the use of convalescent plasma leads to better outcomes in hospitalised patients with less severe disease remains a very important question. Recruitment of such patients will continue in the trial.

This arm of the trial has now paused to enable completion of follow-up of all enrolled participants. The investigators await a more complete analysis based on data from more than 4000 severely ill patients recruited in the trial, including if any subgroups of patients derived benefit from this treatment. These findings are therefore preliminary and may change when all the analyses have been completed.

Manu Shankar-Hari PhD, Professor of Critical Care Medicine at Guy’s and St Thomas’ Hospital London and an NIHR Clinician Scientist, said: “It is biologically plausible that patients who are not producing antibodies at the time of convalescent plasma therapy and those patients with excess virus may benefit more than others. Our additional analyses will explore this. Aside from these severe patients, patients who are moderately ill and patients with immune impairments may benefit. It is therefore vital that plasma donations continue.”

Dr Alexis Turgeon, Critical Care Physician and Scientist at CHU de Québec-Université Laval and Professor of Critical Care Medicine at Université Laval in Québec City, Canada, said: “Why convalescent plasma does not seem to improve outcome in severely ill COVID-19 patients admitted to the ICU is not yet known. We can however hypothesize that the damage to the lungs may be already too advanced in these patients to be slowed down and controlled with the neutralization of the virus by the SARS-CoV-2 antibodies.”

The study is supported in the UK by the National Institute for Health Research (NIHR) and Imperial College London & ICNARC are partners in the EU funded PREPARE consortium.

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This article is based on materials provided by REMAP-CAP co-ordinating centres.