Treating people with convalescent plasma for COVID-19
Professor David Roberts, Associate Medical Director, NHS Blood and Transplant, and Dr Lise Estcourt, Director, Clinical Trials Unit, NHS Blood and Transplant, describe the clinical trials to establish whether convalescent plasma is an effective therapy for patients with COVID-19.
A recent report of 30,000 patients treated with convalescent plasma in the USA suggested that convalescent plasma is safe, but there is insufficient evidence to determine whether convalescent plasma is effective in the treatment of COVID-19.
The global pandemic of the new coronavirus SARS-CoV-2 has provided an unprecedented challenge in modern times for medical services and scientific endeavour. Many members of the College across many specialties have used their skills and experience to support epidemiology and the prevention, diagnosis and treatment of COVID-19. As well as keeping the vital non-COVID-19 work going.
There have been real advances in a very short time, including better ventilation, dexamethasone and remdesivir. Another promising specific antiviral therapy still under trial is also one of the oldest: patients who have had COVID-19 can donate plasma that can be used as a therapy for new patients at different stages of the disease.
Convalescent plasma has already been used in observational studies of patients with severe COVID-19. A recent report of 30,000 patients treated with convalescent plasma in the USA suggested that convalescent plasma is safe, but there is insufficient evidence to determine whether convalescent plasma is effective in the treatment of COVID-19.
In the UK, NHS Blood and Transplant is leading two large randomised control trials (RCTs) of convalescent plasma, in a new programme of work funded by the Department of Health and Social Care. The strategy is to build up a collection of plasma from convalescent donors to provide enough plasma not only for two large-scale RCTs to assess the efficacy and safety of convalescent plasma, but also to provide enough plasma to treat hospitalised and intensive care patients with COVID-19 if the RCTs show efficacy.
This new programme to collect convalescent plasma has required setting up collection for plasma within 23 fixed donor centres and opening three new centres in London. A further 14 new centres will open before January 2021 to increase collection as infections increase in the autumn and winter of 2020. So far, more than 100,000 donors have been contacted and 30,000 people such as Ian Frayling (read his personal account of COVID-19) have attended donation centres, yielding more than 11,000 units of high-titre plasma units and more than 17,000 units of medium-titre plasma. Convalescent plasma for clinical trials will only use plasma that has antibodies in the upper third of the range of anti-spike antibodies.
It is inevitable that completing any trials of therapy in a pandemic is a race against time.
The first trial, REMAP-CAP, is for treatment of community- acquired pneumonia in intensive care. This international trial is randomising intensive care patients across the UK to convalescent plasma to assess whether this treatment decreases the risk of remaining on a ventilator or dying due to COVID-19. The plan is to randomise up to 2,000 participants to this trial. The trial is currently open at 110 hospitals around the country.
Behind every person who becomes severely ill with COVID-19 lies an intensely personal story. Ahmed Bhayat was one of the first people in the UK to receive a transfusion of convalescent plasma. Opposite, he explains how he became ill and participated in the trial.
The second trial is a UK-wide trial of convalescent plasma in all hospitalised patients with COVID-19 and this started in May 2020. Patients in the RECOVERY trial receive the same treatment as in the REMAP-CAP trial: two doses of convalescent plasma. The RECOVERY trial will assess whether convalescent plasma decreases the risk of death or the need for mechanical ventilation for anyone who is hospitalised with COVID-19. The plan is to randomise up to 5,000 participants to this trial and the trial is open at more than 180 hospitals around the UK.
It is inevitable that completing any trials of therapy in a pandemic is a race against time. These trials have proven no exception. The trials of convalescent plasma need a pool of patients who have recovered from acute illness and who have developed antibodies to provide plasma. The trials are likely to report in late 2020 or early 2021. Plasma is being collected to treat patients after the trials have ended and there is likely to be a need for convalescent plasma even after vaccines are available, as uptake and protection are likely to be incomplete. We hope the completion of the trials will define a new, effective therapy for COVID-19.