The NHS Blood and Transplant Clinical Trials Unit is managing the convalescent plasma aspects of the REMAP-CAP and RECOVERY trials.
This page answers some of the common clinical queries about the trials.
Is there a possibility that convalescent plasma will be more effective during the acute phase of virus replication rather than in patients with acute respiratory distress syndrome?
The effectiveness (or otherwise) of convalescent plasma is not yet proven, and this is the purpose of providing convalescent plasma through trials. Each trial is looking at patient treatment in different settings:
- REMAP-CAP is recruiting the most severely ill patients (in intensive care)
- RECOVERY is recruiting patients being treated in hospital
No. It is a theoretical risk. The plasma we are giving has high levels of neutralising antibodies.
Problems occur with antibody dependent enhancement if the antibodies transfused are not neutralising in nature.
Whilst the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) has permitted the use of UK plasma in blood products, there has been no change to its use for fractionation.
However, SaBTO and the Medicines and Healthcare products Regulatory Agency (MHRA) are presently considering if UK plasma donations can be used for manufacture of convalescent plasma immunoglobulin. NHS Blood and Transplant will aim to support, should this use be approved.
At present the clinical trials are only looking at post-infection treatment, but data will be reviewed if it suggests that prophylaxis may warrant further investigation.
REMAP-CAP is recruiting adults only. RECOVERY will include children and neonates.
Could the use of convalescent plasma in the sickest patients only lead to delay in progressing with the RECOVERY trial?
No. Each trial has its own patient recruitment criteria independent of each other.
We will start RECOVERY when we have sufficient plasma to start the trial and hope to begin at the end of May.
The risk for convalescent plasma is the same as the risk for other blood components. SaBTO has decided that pathogen inactivation is not necessary for convalescent plasma after a review of the evidence.
We don’t know yet, this is why we are assessing patients in great detail as part of the trial.
Do you expect patients receiving convalescent plasma to still produce the same antibody response themselves, or is there a danger that their own immune response will be diminished?
We don’t know yet, we will assess this as part of the trial.
Yes. One of our subgroup analyses in REMAP-CAP is to see if it is effective in patients who have already developed antibodies against COVID-19.
REMAP-CAP is for patients in intensive care and who, therefore, are under the highest levels of observation and care.
This provides increased opportunity to observe and also to intervene if necessary.
The reason for doing a trial is that we do not yet know the answer to this question.
Are there any concerns regarding pro-coagulopathic effects with plasma transfusions where the patients have normal or high levels of factors?
We will assess the effect of convalescent plasma on venous thrombotic events up to 90 days after the start of the trial to assess the effect on clinical thrombosis (a blood clot inside a blood vessel).
Is there a cut off for administration with fibrinogen and or Factor v11 levels which can be quite high in these patients?
Should patients on continuous veno-venous hemofiltration be concerned about loss of efficacy of convalescent plasma?
This will be something we can assess as part of the trial.
If the plasma includes donations from multiparous women, is there an increased risk of transfusion-related acute lung injury (TRALI)?
All plasma from female donors is tested for human leukocyte antigen/human platelet antigen as a safety measure to minimise the TRALI risk.
What evidence is there from China that convalescent plasma is therapeutically beneficial for COVID-19 patients?
A rapid systematic review of the evidence is about to be published by Cochrane which summarises the evidence.
Contraindications are a previous history of moderate or severe allergy to blood components and a previous history of TRALI. Or a known objection to receiving plasma containing blood components.
If the patient has a severe reaction that could be TRALI or bacterial contamination it needs to be quarantined and usual investigations made. Standard methods for referral apply.
All transfusion related adverse reactions should be reported in the usual way (to SHOT/SABRE). In addition, serious adverse reactions following convalescent plasma transfusion should also be reported to the relevant trial team.