Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19

Cohort 1: Elderly and high COVID-age population: Inclusion criteria: * SARS-CoV-2 RNA detected in a specimen, ≤ 7 days after onset of symptoms * Symptoms of COVID-19 (so including but not limited to: fever; cough; breathlessness; chest pain; wheeze; sore throat; haemoptysis; runny nose; fatigue; muscle or joint pain; confusion; headache; seizures; nausea; vomiting; diarrhoea; abdominal pain; poor appetite; skin ulcers or rash; ear pain; conjunctivitis; anosmia; bleeding; lymphadenopathy. The attending clinician will determine if symptoms are consistent with COVID-19. * Clinical status not requiring admission to hospital for COVID-19 disease and oxygen support * Ability to transfuse (per randomisation) within 7 days after onset of symptoms * Men or women, 70 years or older OR * under 70 years with significant comorbidities (arterial hypertension, diabetes, obesity, asthma or other chronic pulmonary disease, cardiovascular disease, cerebrovascular disease, chronic kidney disease / dialysis, hemoglobinopathies, liver disease, chronic neurological disease, rheumatoid arthritis, lupus or psoriasis) resulting in a 'COVID-age' of 70 years or more according to the ALAMA risk calculator https://alama.org.uk/covid-19-medical-risk-assessment/ Exclusion Criteria: * Age \< 18 years (France and Germany only) * Prior or concurrent treatment for COVID-19 (unless listed as authorized) * History of COVID-19 disease in the last 90 days prior to enrollment * Prior anti-SARS-CoV-2 immunization * Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components * Known participant objection to receiving plasma products * Primary or acquired immune deficiency listed below (see cohort 2) * Refusal to participate expressed by patient or legally authorised representative * Pregnancy Cohort 2: High-risk immunocompromised population Inclusion criteria: * SARS-CoV-2 RNA, or positive antigenic test, detected in a specimen, ≤ 7 days after onset of symptoms * Symptoms of COVID-19 (so including but not limited to: fever; cough; breathlessness; chest pain; wheeze; sore throat; haemoptysis; runny nose; fatigue; muscle or joint pain; confusion; headache; seizures; nausea; vomiting; diarrhoea; abdominal pain; poor appetite; skin ulcers or rash; ear pain; conjunctivitis; anosmia; bleeding; lymphadenopathy. The attending clinician will determine if symptoms are consistent with COVID-19. * Clinical status not requiring admission to hospital for COVID-19 disease and oxygen support * Ability to transfuse (per randomisation) within 7 days after onset of symptoms * Male or female with extremely high risk including: a. Patients with at least one of the following acquired immune deficiencies i. Lymphoid malignancies treated within the last 12 months ii. Lymphoid malignancies with persistent hypogammaglobulinaemia (IgG \< 5g/L) iii. Myeloid malignancies treated by chemotherapy within the last 12 months iv. Myeloid malignancies treated by anti-BCL-2 drugs within the last 12 months v. Myeloid malignancies associated with prolonged neutropenia (≥ 6 weeks) vi. Solid tumour undergoing treatment with chemotherapy (until 3 months after completion of the last chemotherapy cycle) vii. Allogenic hematopoietic stem cell transplantation within the last 12 months or anytime if on-going treatment for chronic GVHD viii. Organ transplantation ix. Anti-B (CD20/CD19) MoAb and/or mycophenolate mofetil treatment within the last 12 months x. Anti-CD19/CD20 CAR-T cell treatment xi. ATG or alemtuzumab treatment within the last 6 months xii. AIDS OR b. Patients with primary lymphoid immune deficiencies. i. B cell deficiencies (such as Bruton agammaglobulinemia) ii. T cell deficiencies (such as Wiskott Aldrich disease) iii. Combined deficiencies (such as Common variable immunodeficiency). OR c. Patients without detectable seroconversion ≥ 3 weeks after complete vaccination schedule with an approved vaccine. Exclusion Criteria: * Age \< 18 years (France and Germany only) * Prior or concurrent treatment for COVID-19 (dexamethasone, anti-IL-6/IL6R, remdesivir) except for prophylactic administration of anti-SARS-CoV-2 monoclonal antibodies (pre or post exposure) and authorized specific treatment * History of COVID-19 disease in the last 90 days prior to enrollment * Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components * Known participant objection to receiving plasma products * Refusal to participate expressed by patient or legally authorised representative * Pregnancy