Title: The use of convalescent plasma to treat hospitalised and critically ill patients with COVID-19 disease
Funder: Department of Health and Social Care

Abstract: 1.2 Scientific/technical summary (max. 250 words) The COVID-19 pandemic caused by SARS-CoV2 includes a wide spectrum of disease - ranging from mild self-limiting symptoms to critical illness. Estimated case-fatality is 1.5- 2.5%, overall, but 50% in patients admitted to ICU. Current management of patients is exclusively supportive, and there is an urgent need for definitive therapies. We hypothesise that specific antibodies against SARS-CoV-2 in convalescent plasma increase viral clearance and reduce mortality. We have DHSE funding for large-scale convalescent plasma (CP) collection, to conduct randomised clinical trials (RCTs). First, in REMAP-CAP, will enrol 1000 ICU COVID-19 patients randomised to convalescent plasma and 1000 controls, powered to detect a 20% relative reduction in mortality. After the safety of convalescent plasma is confirmed in 200 patients in REMAP-CAP, we will immediately enrol up to 5000 patients in the RECOVERY trial, aiming to show a 20% reduction in mortality or ventilation. This proposal supports both trials and target keys scientific aims. In REMAP-CAP, we will determine rates of viral clearance, anti-SARS- CoV-2 antibody trajectory and cytokine profile and immunological phenotypes before and after convalescent plasma, to examine differences the immune response between 200 plasma recipients and 200 controls. These data will establish causal associations between therapy and viral clearance, pharmacokinetics of transferred antibody, and identify the relationship of virological, immunological and clinical outcomes with transferred antibodies. We will define B-, T-cell and dendritic cell function in a sub-set, and antibody responses in all donors, and relate these to clinical outcomes. These data will not only provide evidence for the efficacy of passive immunotherapy with convalescent plasma, but also inform future development of hyperimmune globulin and human mAbs. 1.3. Lay summary (max. 200 words) Most people who have an infection with COVID-19 will have a mild illness and recover with rest. However, some people will become critically ill and need to go to hospital, this is often due to problems with breathing. Patients who recover from the virus develop antibodies in their blood which prevent future infections. It is possible to safely collect blood plasma from these people and this convalescent plasma can be safely given to other people with the disease to help them recover. This trial will see if this technique reduces the number of deaths due to COVID-19. We will identify 2000 patients and give 1000 the antibodies to see if they have a better outcome compared to 1000 with normal care. We will also collect information on how the virus is cleared from the body and what specific antibodies are useful. As soon as we know the therapy is safe, we will also enrol up to 5000 patients in a second trial to see if convalescent plasma helps people admitted to hospital wards with COVID-19.

Lay abstract: 1.2 Scientific/technical summary (max. 250 words) The COVID-19 pandemic caused by SARS-CoV2 includes a wide spectrum of disease - ranging from mild self-limiting symptoms to critical illness. Estimated case-fatality is 1.5- 2.5%, overall, but 50% in patients admitted to ICU. Current management of patients is exclusively supportive, and there is an urgent need for definitive therapies. We hypothesise that specific antibodies against SARS-CoV-2 in convalescent plasma increase viral clearance and reduce mortality. We have DHSE funding for large-scale convalescent plasma (CP) collection, to conduct randomised clinical trials (RCTs). First, in REMAP-CAP, will enrol 1000 ICU COVID-19 patients randomised to convalescent plasma and 1000 controls, powered to detect a 20% relative reduction in mortality. After the safety of convalescent plasma is confirmed in 200 patients in REMAP-CAP, we will immediately enrol up to 5000 patients in the RECOVERY trial, aiming to show a 20% reduction in mortality or ventilation. This proposal supports both trials and target keys scientific aims. In REMAP-CAP, we will determine rates of viral clearance, anti-SARS- CoV-2 antibody trajectory and cytokine profile and immunological phenotypes before and after convalescent plasma, to examine differences the immune response between 200 plasma recipients and 200 controls. These data will establish causal associations between therapy and viral clearance, pharmacokinetics of transferred antibody, and identify the relationship of virological, immunological and clinical outcomes with transferred antibodies. We will define B-, T-cell and dendritic cell function in a sub-set, and antibody responses in all donors, and relate these to clinical outcomes. These data will not only provide evidence for the efficacy of passive immunotherapy with convalescent plasma, but also inform future development of hyperimmune globulin and human mAbs. 1.3. Lay summary (max. 200 words) Most people who have an infection with COVID-19 will have a mild illness and recover with rest. However, some people will become critically ill and need to go to hospital, this is often due to problems with breathing. Patients who recover from the virus develop antibodies in their blood which prevent future infections. It is possible to safely collect blood plasma from these people and this convalescent plasma can be safely given to other people with the disease to help them recover. This trial will see if this technique reduces the number of deaths due to COVID-19. We will identify 2000 patients and give 1000 the antibodies to see if they have a better outcome compared to 1000 with normal care. We will also collect information on how the virus is cleared from the body and what specific antibodies are useful. As soon as we know the therapy is safe, we will also enrol up to 5000 patients in a second trial to see if convalescent plasma helps people admitted to hospital wards with COVID-19.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION