Patients are excluded from the study if any of the following criteria apply (or any of the criteria from the appropriate sub-protocol): 1. Patients who have previously had a score of 6 or 7 on the 9-point ordinal scale. 2. Any patient whose interests are not best served by study participation, as determined by a senior attending clinician. 3. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × the upper limit of normal (ULN). 4. Known active infection with HIV or hepatitis B or C. 5. Stage 4 severe chronic kidney disease. 6. Allergy to any study medication. 7. Experimental off-label usage of medicinal products as treatments for COVID-19 (except where the product has either been given a positive opinion under the Early Access to Medicines Scheme [EAMS] or is a SARS-CoV-2 vaccine) at the time of enrolment. 8. Patients participating in another clinical study of an investigational medicinal product, unless co-enrolment in the other study has been pre-approved by the Sponsor and Chief Investigator. 9. Active tuberculosis defined as requiring current treatment for tuberculosis. Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-002: X1. Inability to swallow capsules (administration via nasogastric tube is permitted in patients who become unable to swallow after starting the study drug) X2. Patients with a permanent cardiac pacemaker implanted. X3. History of the following cardiac conditions: a) Myocardial infarction within 3 months prior to the first dose b) Unstable angina c) History of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia [≤55 bpm]), left bundle branch block, or ventricular arrhythmia) or history of familial long QT. Patients with an implantable cardioverter defibrillator device in place, will be allowed to enrol. Atrial fibrillation will not be a reason for exclusion. X4. Screening 12-lead ECG with a measurable QTc interval according to Fridericia correction (QTcF) >470 msec In the presence of a temporary cardiac pacemaker, QTcF will need to be calculated from an ECG which has been recorded during a period where ventricular (QRS) complexes without pacing are present. If no unpaced ventricular complexes are present to allow calculation of QTcF, the patient should not be enrolled in this sub-protocol. X5. Clinically significant hypokalaemia. Individuals who do not meet this criterion may be rescreened once, after correction of electrolyte abnormality X6. Therapeutic anticoagulation with vitamin K antagonists. Note: Patients receiving low doses prescribed to maintain the patency of venous access devices may be included. X7. Previous bowel resection that would interfere with drug absorption Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-003: X1. A known history of myocardial infarction within 3 months prior to the first dose X2. A known history of heart failure defined as either of the following: a) ≥2 first degree relatives with clinically significant heart failure, or b) ≥1 first degree relative with heart failure known to be heritable (eg, hypertrophic cardiomyopathy), unless inheritance was previously excluded by genetic testing Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-006: X1.Participants with unresolved or suspected infection with Neisseria meningitidis, or a past history of Neisseria meningitidis (eg, in a complement deficient patient), should not receive treatment with zilucoplan.

Patients are excluded from the study if any of the following criteria apply (or any of the criteria from the appropriate sub-protocol): 1. Patients who have previously had a score of 6 or 7 on the 9-point ordinal scale. 2. Any patient whose interests are not best served by study participation, as determined by a senior attending clinician. 3. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × the upper limit of normal (ULN). 4. Known active infection with HIV or hepatitis B or C. 5. Stage 4 severe chronic kidney disease. 6. Allergy to any study medication. 7. Experimental off-label usage of medicinal products as treatments for COVID-19 (except where the product has either been given a positive opinion under the Early Access to Medicines Scheme [EAMS] or is a SARS-CoV-2 vaccine) at the time of enrolment. 8. Patients participating in another clinical study of an investigational medicinal product, unless co-enrolment in the other study has been pre-approved by the Sponsor and Chief Investigator. 9. Active tuberculosis defined as requiring current treatment for tuberculosis. Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-002: X1. Inability to swallow capsules (administration via nasogastric tube is permitted in patients who become unable to swallow after starting the study drug) X2. Patients with a permanent cardiac pacemaker implanted. X3. History of the following cardiac conditions: a) Myocardial infarction within 3 months prior to the first dose b) Unstable angina c) History of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia [≤55 bpm]), left bundle branch block, or ventricular arrhythmia) or history of familial long QT. Patients with an implantable cardioverter defibrillator device in place, will be allowed to enrol. Atrial fibrillation will not be a reason for exclusion. X4. Screening 12-lead ECG with a measurable QTc interval according to Fridericia correction (QTcF) >470 msec In the presence of a temporary cardiac pacemaker, QTcF will need to be calculated from an ECG which has been recorded during a period where ventricular (QRS) complexes without pacing are present. If no unpaced ventricular complexes are present to allow calculation of QTcF, the patient should not be enrolled in this sub-protocol. X5. Clinically significant hypokalaemia. Individuals who do not meet this criterion may be rescreened once, after correction of electrolyte abnormality X6. Therapeutic anticoagulation with vitamin K antagonists. Note: Patients receiving low doses prescribed to maintain the patency of venous access devices may be included. X7. Previous bowel resection that would interfere with drug absorption Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-003: X1. A known history of myocardial infarction within 3 months prior to the first dose X2. A known history of heart failure defined as either of the following: a) ≥2 first degree relatives with clinically significant heart failure, or b) ≥1 first degree relative with heart failure known to be heritable (eg, hypertrophic cardiomyopathy), unless inheritance was previously excluded by genetic testing Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-006: X1.Participants with unresolved or suspected infection with Neisseria meningitidis, or a past history of Neisseria meningitidis (eg, in a complement deficient patient), should not receive treatment with zilucoplan.

Patients are excluded from the study if any of the following criteria apply (or any of the criteria from the appropriate sub-protocol): 1. Patients who have previously had a score of 6 or 7 on the 9-point ordinal scale. 2. Any patient whose interests are not best served by study participation, as determined by a senior attending clinician. 3. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × the upper limit of normal (ULN). 4. Known active infection with HIV or hepatitis B or C. 5. Stage 4 severe chronic kidney disease. 6. Anticipated transfer to another hospital that is not a study centre within 72 hours. 7. Allergy to any study medication. 8. Experimental off-label usage of medicinal products as treatments for COVID-19 (except where the product has either been given a positive opinion under the Early Access to Medicines Scheme [EAMS] or is a SARS-CoV-2 vaccine) at the time of enrolment. 9. Patients participating in another clinical study of an investigational medicinal product, unless co-enrolment in the other study has been pre-approved by the Steering Committee. 10. Active tuberculosis defined as requiring current treatment for tuberculosis. Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-002: 11. Inability to swallow capsules (administration via nasogastric tube is permitted in patients who become unable to swallow after starting the study drug) 12. Patients with a permanent cardiac pacemaker implanted. 13. History of the following cardiac conditions: a) Myocardial infarction within 3 months prior to the first dose b) Unstable angina c) History of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia [≤55 bpm]), left bundle branch block, or ventricular arrhythmia) or history of familial long QT. Patients with an implantable cardioverter defibrillator device in place, will be allowed to enrol. Atrial fibrillation will not be a reason for exclusion. 14. Screening 12-lead ECG with a measurable QTc interval according to Fridericia correction (QTcF) >470 msec In the presence of a temporary cardiac pacemaker, QTcF will need to be calculated from an ECG which has been recorded during a period where ventricular (QRS) complexes without pacing are present. If no unpaced ventricular complexes are present to allow calculation of QTcF, the patient should not be enrolled in this sub-protocol. 15. Clinically significant hypokalaemia. Individuals who do not meet this criterion may be rescreened once, after correction of electrolyte abnormality 16. Therapeutic anticoagulation with vitamin K antagonists. Note: Patients receiving low doses prescribed to maintain the patency of venous access devices may be included. 17. Previous bowel resection that would interfere with drug absorption Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-003: 18. Active tuberculosis defined as requiring current treatment for tuberculosis Active tuberculosis defined as requiring current treatment for tuberculosis 19. A known family history of heart failure defined as either of the following: a) ≥2 first degree relatives with clinically significant heart failure, or b) ≥1 first degree relative with heart failure known to be heritable (eg, hypertrophic cardiomyopathy), unless inheritance was previously excluded by genetic testing Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-004: Unable to take acalabrutinib by mouth Profound neutropenia and/or profound thrombocytopenia as defined as an absolute neutrophil count < 500/µL and platelet count < 50,000/µL respectively at screening per local laboratory Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-006: 20.Participants with unresolved or suspected infection with Neisseria meningitidis, or a past history of Neisseria meningitidis (eg, in a complement deficient patient), should not receive treatment with zilucoplan. For Sub study ACCORD 2-005, please refer to the Master protocol. For Sub study ACCORD 2-008, please refer to the Master protocol.

Patients are excluded from the study if any of the following criteria apply (or any of the criteria from the appropriate sub-protocol): 1. Patients who have previously had a score of 6 or 7 on the 9-point ordinal scale. 2. Any patient whose interests are not best served by study participation, as determined by a senior attending clinician. 3. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × the upper limit of normal (ULN). 4. Known active infection with HIV or hepatitis B or C. 5. Stage 4 severe chronic kidney disease. 6. Anticipated transfer to another hospital that is not a study centre within 72 hours. 7. Allergy to any study medication. 8. Experimental off-label usage of medicinal products as treatments for COVID-19 (except where the product has either been given a positive opinion under the Early Access to Medicines Scheme [EAMS] or is a SARS-CoV-2 vaccine) at the time of enrolment. 9. Patients participating in another clinical study of an investigational medicinal product, unless co-enrolment in the other study has been pre-approved by the Steering Committee. 10. Active tuberculosis defined as requiring current treatment for tuberculosis. Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-002: 11. Inability to swallow capsules (administration via nasogastric tube is permitted in patients who become unable to swallow after starting the study drug) 12. Patients with a permanent cardiac pacemaker implanted. 13. History of the following cardiac conditions: a) Myocardial infarction within 3 months prior to the first dose b) Unstable angina c) History of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia [≤55 bpm]), left bundle branch block, or ventricular arrhythmia) or history of familial long QT. Patients with an implantable cardioverter defibrillator device in place, will be allowed to enrol. Atrial fibrillation will not be a reason for exclusion. 14. Screening 12-lead ECG with a measurable QTc interval according to Fridericia correction (QTcF) >470 msec In the presence of a temporary cardiac pacemaker, QTcF will need to be calculated from an ECG which has been recorded during a period where ventricular (QRS) complexes without pacing are present. If no unpaced ventricular complexes are present to allow calculation of QTcF, the patient should not be enrolled in this sub-protocol. 15. Clinically significant hypokalaemia. Individuals who do not meet this criterion may be rescreened once, after correction of electrolyte abnormality 16. Therapeutic anticoagulation with vitamin K antagonists. Note: Patients receiving low doses prescribed to maintain the patency of venous access devices may be included. 17. Previous bowel resection that would interfere with drug absorption Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-003: 18. Active tuberculosis defined as requiring current treatment for tuberculosis Active tuberculosis defined as requiring current treatment for tuberculosis 19. A known family history of heart failure defined as either of the following: a) ≥2 first degree relatives with clinically significant heart failure, or b) ≥1 first degree relative with heart failure known to be heritable (eg, hypertrophic cardiomyopathy), unless inheritance was previously excluded by genetic testing Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-004: Unable to take acalabrutinib by mouth Profound neutropenia and/or profound thrombocytopenia as defined as an absolute neutrophil count < 500/µL and platelet count < 50,000/µL respectively at screening per local laboratory Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-006: 20.Participants with unresolved or suspected infection with Neisseria meningitidis, or a past history of Neisseria meningitidis (eg, in a complement deficient patient), should not receive treatment with zilucoplan. For Sub study ACCORD 2-005, please refer to the Master protocol. For Sub study ACCORD 2-008, please refer to the Master protocol.