a. core platform exclusions (all participants must not meet the following): 1. death is deemed to be imminent and inevitable during the next 24 hours and one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment 2. patient is expected to be discharged from hospital today or tomorrow 3. more than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to proven sars-cov-2 infection 4. previous participation in this trial, or another trial that is analysed within the same statistical model as this trial, within the last 90 days b. antiviral ii domain exclusions (patients at sites participating in the antiviral ii domain must not meet the following): 1. severe renal impairment, defined as egfr\<30ml/min or receipt of renal replacement therapy 2. severe hepatic impairment, defined as proven or suspected cirrhosis with child pugh class of c, or acute hepatitis, defined as ast or alt\>5 times the upper limit of normal in the testing laboratory. 3. the patient has received, at the time of eligibility assessment, \>24h of an antiviral agent intended to have activity against sars-cov-2, within the past 7 days 4. the patient is known to be pregnant or breastfeeding 5. the treating clinician believes that participation in the domain would not be in the best interests of the patient b.1. antiviral ii domain non-immune suppressed stratum-specific exclusion criteria (all non-immune suppressed patients at sites participating in the antiviral ii domain must not meet the following): 1. onset of covid-related symptoms was more than 7 days (i.e., 168 hours) ago b2. antiviral ii domain intervention-specific exclusion criteria (all patients at sites participating in the antiviral ii domain will be excluded from the below interventions if they meet the following): will be excluded from receiving remdesivir if: 1. no venous access is available and none can be created 2. known hypersensitivity to remdesivir or its excipients will be excluded from receiving nirmatrelvir/ritonavir if: 1. the patient is unable to take, tolerate or absorb oral or enteral medications 2. known hypersensitivity to any of nirmatrelvir, ritonavir or its excipients 3. receipt of a concomitant drug with a high-risk interaction with nirmatrelvir-ritonavir which cannot be ceased or substituted. will be excluded from receiving no antiviral agent if: 1. the patient is in the immune suppressed stratum 2. the patient is receiving or has received supplemental oxygen on the calendar day of eligibility assessment. 3. the patient is considered by the treating clinician to be at very high risk for progression to severe covid-19

a. core platform exclusions (all participants must not meet the following): 1. death is deemed to be imminent and inevitable during the next 24 hours and one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment 2. patient is expected to be discharged from hospital today or tomorrow 3. more than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to proven sars-cov-2 infection 4. previous participation in this trial, or another trial that is analysed within the same statistical model as this trial, within the last 90 days b. antiviral ii domain exclusions (patients at sites participating in the antiviral ii domain must not meet the following): 1. severe renal impairment, defined as egfr\<30ml/min or receipt of renal replacement therapy 2. severe hepatic impairment, defined as proven or suspected cirrhosis with child pugh class of c, or acute hepatitis, defined as ast or alt\>5 times the upper limit of normal in the testing laboratory. 3. the patient has received, at the time of eligibility assessment, \>24h of an antiviral agent intended to have activity against sars-cov-2, within the past 7 days 4. the patient is known to be pregnant or breastfeeding 5. the treating clinician believes that participation in the domain would not be in the best interests of the patient b.1. antiviral ii domain non-immune suppressed stratum-specific exclusion criteria (all non-immune suppressed patients at sites participating in the antiviral ii domain must not meet the following): 1. onset of covid-related symptoms was more than 7 days (i.e., 168 hours) ago b2. antiviral ii domain intervention-specific exclusion criteria (all patients at sites participating in the antiviral ii domain will be excluded from the below interventions if they meet the following): will be excluded from receiving remdesivir if: 1. no venous access is available and none can be created 2. known hypersensitivity to remdesivir or its excipients will be excluded from receiving nirmatrelvir/ritonavir if: 1. the patient is unable to take, tolerate or absorb oral or enteral medications 2. known hypersensitivity to any of nirmatrelvir, ritonavir or its excipients 3. receipt of a concomitant drug with a high-risk interaction with nirmatrelvir-ritonavir which cannot be ceased or substituted. will be excluded from receiving no antiviral agent if: 1. the patient is in the immune suppressed stratum 2. the patient is receiving or has received supplemental oxygen on the calendar day of eligibility assessment. 3. the patient is considered by the treating clinician to be at very high risk for progression to severe covid-19

a. core platform exclusions (all participants must not meet the following): death is deemed to be imminent and inevitable during the next 24 hours and one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment patient is expected to be discharged from hospital today or tomorrow more than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to proven sars-cov-2 infection previous participation in this trial, or another trial that is analysed within the same statistical model as this trial, within the last 90 days b. antiviral ii domain exclusions (patients at sites participating in the antiviral ii domain must not meet the following): severe renal impairment, defined as egfr<30ml/min or receipt of renal replacement therapy severe hepatic impairment, defined as proven or suspected cirrhosis with child pugh class of c, or acute hepatitis, defined as ast or alt>5 times the upper limit of normal in the testing laboratory. the patient has received, at the time of eligibility assessment, >24h of an antiviral agent intended to have activity against sars-cov-2, within the past 7 days the patient is known to be pregnant or breastfeeding the treating clinician believes that participation in the domain would not be in the best interests of the patient b.1. antiviral ii domain non-immune suppressed stratum-specific exclusion criteria (all non-immune suppressed patients at sites participating in the antiviral ii domain must not meet the following): 1. onset of covid-related symptoms was more than 7 days (i.e., 168 hours) ago b2. antiviral ii domain intervention-specific exclusion criteria (all patients at sites participating in the antiviral ii domain will be excluded from the below interventions if they meet the following): will be excluded from receiving remdesivir if: no venous access is available and none can be created known hypersensitivity to remdesivir or its excipients will be excluded from receiving nirmatrelvir/ritonavir if: the patient is unable to take, tolerate or absorb oral or enteral medications known hypersensitivity to any of nirmatrelvir, ritonavir or its excipients receipt of a concomitant drug with a high-risk interaction with nirmatrelvir-ritonavir which cannot be ceased or substituted. will be excluded from receiving no antiviral agent if: the patient is in the immune suppressed stratum the patient is receiving or has received supplemental oxygen on the calendar day of eligibility assessment. the patient is considered by the treating clinician to be at very high risk for progression to severe covid-19

a. core platform exclusions (all participants must not meet the following): death is deemed to be imminent and inevitable during the next 24 hours and one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment patient is expected to be discharged from hospital today or tomorrow more than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to proven sars-cov-2 infection previous participation in this trial, or another trial that is analysed within the same statistical model as this trial, within the last 90 days b. antiviral ii domain exclusions (patients at sites participating in the antiviral ii domain must not meet the following): severe renal impairment, defined as egfr<30ml/min or receipt of renal replacement therapy severe hepatic impairment, defined as proven or suspected cirrhosis with child pugh class of c, or acute hepatitis, defined as ast or alt>5 times the upper limit of normal in the testing laboratory. the patient has received, at the time of eligibility assessment, >24h of an antiviral agent intended to have activity against sars-cov-2, within the past 7 days the patient is known to be pregnant or breastfeeding the treating clinician believes that participation in the domain would not be in the best interests of the patient b.1. antiviral ii domain non-immune suppressed stratum-specific exclusion criteria (all non-immune suppressed patients at sites participating in the antiviral ii domain must not meet the following): 1. onset of covid-related symptoms was more than 7 days (i.e., 168 hours) ago b2. antiviral ii domain intervention-specific exclusion criteria (all patients at sites participating in the antiviral ii domain will be excluded from the below interventions if they meet the following): will be excluded from receiving remdesivir if: no venous access is available and none can be created known hypersensitivity to remdesivir or its excipients will be excluded from receiving nirmatrelvir/ritonavir if: the patient is unable to take, tolerate or absorb oral or enteral medications known hypersensitivity to any of nirmatrelvir, ritonavir or its excipients receipt of a concomitant drug with a high-risk interaction with nirmatrelvir-ritonavir which cannot be ceased or substituted. will be excluded from receiving no antiviral agent if: the patient is in the immune suppressed stratum the patient is receiving or has received supplemental oxygen on the calendar day of eligibility assessment. the patient is considered by the treating clinician to be at very high risk for progression to severe covid-19

a. overall platform exclusions: currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. previous participation in the trial treating team deems enrolment in the study is not in the best interests of the patient death is deemed to be imminent and inevitable within the next 24 hours either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: known current decompensated liver disease (child-pugh b or c) the treating clinician intends to continue or commence therapeutic anticoagulation a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) hypersensitivity to nafamostat pregnancy or breastfeeding currently receiving or have received nafamostat in the past 7 days decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody - hyperimmunoglobulin or standard care) specific exclusions: participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment treating team deems enrolment in antibody intervention is not in the best interests of the patient. participant has received a sars-cov-2 vaccine within the prior 30 days known previous history of serious allergic reaction to blood product transfusion, intravenous immunoglobulin or other injectable form of igg will exclude a patient from hyperimmune globulin known personal or religious objections to receiving blood products will exclude a patient from hyperimmune globulin pregnant or breastfeeding female participants will be excluded from hyperimmune globulin prior history of a thrombotic event (including acute coronary syndromes, cerebrovascular syndromes, pulmonary or deep vein thrombosis) within the prior 30 days of randomisation will exclude a patient from receiving hyperimmune globulin having a creatinine clearance of less than 50ml/min will exclude a patient from receiving hyperimmune globulin d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: receiving dual antiplatelet therapy the treating clinician intends to continue or commence therapeutic anticoagulation contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity severe thrombocytopenia (platelet count less than 530 x 109/l) history of intracranial haemorrhage in the previous 3 months severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation

a. overall platform exclusions: currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. previous participation in the trial treating team deems enrolment in the study is not in the best interests of the patient death is deemed to be imminent and inevitable within the next 24 hours either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: known current decompensated liver disease (child-pugh b or c) the treating clinician intends to continue or commence therapeutic anticoagulation a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) hypersensitivity to nafamostat pregnancy or breastfeeding currently receiving or have received nafamostat in the past 7 days decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody - hyperimmunoglobulin or standard care) specific exclusions: participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment treating team deems enrolment in antibody intervention is not in the best interests of the patient. participant has received a sars-cov-2 vaccine within the prior 30 days known previous history of serious allergic reaction to blood product transfusion, intravenous immunoglobulin or other injectable form of igg will exclude a patient from hyperimmune globulin known personal or religious objections to receiving blood products will exclude a patient from hyperimmune globulin pregnant or breastfeeding female participants will be excluded from hyperimmune globulin prior history of a thrombotic event (including acute coronary syndromes, cerebrovascular syndromes, pulmonary or deep vein thrombosis) within the prior 30 days of randomisation will exclude a patient from receiving hyperimmune globulin having a creatinine clearance of less than 50ml/min will exclude a patient from receiving hyperimmune globulin d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: receiving dual antiplatelet therapy the treating clinician intends to continue or commence therapeutic anticoagulation contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity severe thrombocytopenia (platelet count less than 530 x 109/l) history of intracranial haemorrhage in the previous 3 months severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation

a. overall platform exclusions: currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. previous participation in the trial treating team deems enrolment in the study is not in the best interests of the patient death is deemed to be imminent and inevitable within the next 24 hours either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: known current decompensated liver disease (child-pugh b or c) the treating clinician intends to continue or commence therapeutic anticoagulation a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) hypersensitivity to nafamostat pregnancy or breastfeeding currently receiving or have received nafamostat in the past 7 days decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody) domain-level exclusions: patients will be excluded from this domain if they have any of the following: participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment; treating team deems enrolment in antibody intervention is not in the best interests of the patient. participant has received a sars-cov-2 vaccine within the prior 30 days domain b (antibody) intervention-level exclusions: the following are intervention exclusions: known previous history of serious allergic reaction to blood product transfusion, intravenous immunoglobulin or other injectable form of igg will exclude a patient from hyperimmune globulin; known personal or religious objections to receiving blood products will exclude a patient from receiving hyperimmune globulin; prior history of a thrombotic event (including acute coronary sydromes, cerebrovascular syndromes, pulmonary or deep venous thrombosis) within the prior 30 days of randomisations will exclude a patient from hyperimmune globulin; having a creatinine clearance of less than 50ml/min will exclude a patient from receiving hyperimmune globulin d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: receiving dual antiplatelet therapy the treating clinician intends to continue or commence therapeutic anticoagulation contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity severe thrombocytopenia (platelet count less than 530 x 109/l) history of intracranial haemorrhage in the previous 3 months severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation

a. overall platform exclusions: currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. previous participation in the trial treating team deems enrolment in the study is not in the best interests of the patient death is deemed to be imminent and inevitable within the next 24 hours either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: known current decompensated liver disease (child-pugh b or c) the treating clinician intends to continue or commence therapeutic anticoagulation a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) hypersensitivity to nafamostat pregnancy or breastfeeding currently receiving or have received nafamostat in the past 7 days decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody) domain-level exclusions: patients will be excluded from this domain if they have any of the following: participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment; treating team deems enrolment in antibody intervention is not in the best interests of the patient. participant has received a sars-cov-2 vaccine within the prior 30 days domain b (antibody) intervention-level exclusions: the following are intervention exclusions: known previous history of serious allergic reaction to blood product transfusion, intravenous immunoglobulin or other injectable form of igg will exclude a patient from hyperimmune globulin; known personal or religious objections to receiving blood products will exclude a patient from receiving hyperimmune globulin; prior history of a thrombotic event (including acute coronary sydromes, cerebrovascular syndromes, pulmonary or deep venous thrombosis) within the prior 30 days of randomisations will exclude a patient from hyperimmune globulin; having a creatinine clearance of less than 50ml/min will exclude a patient from receiving hyperimmune globulin d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: receiving dual antiplatelet therapy the treating clinician intends to continue or commence therapeutic anticoagulation contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity severe thrombocytopenia (platelet count less than 530 x 109/l) history of intracranial haemorrhage in the previous 3 months severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation

a. overall platform exclusions: 1. currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. 2. previous participation in the trial 3. treating team deems enrolment in the study is not in the best interests of the patient 4. death is deemed to be imminent and inevitable within the next 24 hours 5. either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: - known current decompensated liver disease (child-pugh b or c) - the treating clinician intends to continue or commence therapeutic anticoagulation - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation - serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - hypersensitivity to nafamostat - pregnancy or breastfeeding - currently receiving or have received nafamostat in the past 7 days - decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment; - treating team deems enrolment in antibody intervention is not in the best interests of the patient. - participant has received a sars-cov-2 vaccine within the prior 30 days domain b (antibody) intervention-level exclusions: the following are intervention exclusions: - known previous history of serious allergic reaction to blood product transfusion, intravenous immunoglobulin or other injectable form of igg will exclude a patient from hyperimmune globulin; - known personal or religious objections to receiving blood products will exclude a patient from receiving hyperimmune globulin; - prior history of a thrombotic event (including acute coronary sydromes, cerebrovascular syndromes, pulmonary or deep venous thrombosis) within the prior 30 days of randomisations will exclude a patient from hyperimmune globulin; - having a creatinine clearance of less than 50ml/min will exclude a patient from receiving hyperimmune globulin d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - receiving dual antiplatelet therapy - the treating clinician intends to continue or commence therapeutic anticoagulation - contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity - severe thrombocytopenia (platelet count less than 530 x 109/l) - history of intracranial haemorrhage in the previous 3 months - severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation

a. overall platform exclusions: 1. currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. 2. previous participation in the trial 3. treating team deems enrolment in the study is not in the best interests of the patient 4. death is deemed to be imminent and inevitable within the next 24 hours 5. either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: - known current decompensated liver disease (child-pugh b or c) - the treating clinician intends to continue or commence therapeutic anticoagulation - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation - serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - hypersensitivity to nafamostat - pregnancy or breastfeeding - currently receiving or have received nafamostat in the past 7 days - decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment; - treating team deems enrolment in antibody intervention is not in the best interests of the patient. - participant has received a sars-cov-2 vaccine within the prior 30 days domain b (antibody) intervention-level exclusions: the following are intervention exclusions: - known previous history of serious allergic reaction to blood product transfusion, intravenous immunoglobulin or other injectable form of igg will exclude a patient from hyperimmune globulin; - known personal or religious objections to receiving blood products will exclude a patient from receiving hyperimmune globulin; - prior history of a thrombotic event (including acute coronary sydromes, cerebrovascular syndromes, pulmonary or deep venous thrombosis) within the prior 30 days of randomisations will exclude a patient from hyperimmune globulin; - having a creatinine clearance of less than 50ml/min will exclude a patient from receiving hyperimmune globulin d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - receiving dual antiplatelet therapy - the treating clinician intends to continue or commence therapeutic anticoagulation - contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity - severe thrombocytopenia (platelet count less than 530 x 109/l) - history of intracranial haemorrhage in the previous 3 months - severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation

a. overall platform exclusions: 1. currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. 2. previous participation in the trial 3. treating team deems enrolment in the study is not in the best interests of the patient 4. death is deemed to be imminent and inevitable within the next 24 hours 5. either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: - known current decompensated liver disease (child-pugh b or c) - the treating clinician intends to continue or commence therapeutic anticoagulation - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation - serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - hypersensitivity to nafamostat - pregnancy or breastfeeding - currently receiving or have received nafamostat in the past 7 days - decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment; - treating team deems enrolment in antibody intervention is not in the best interests of the patient. domain b (antibody) intervention-level exclusions: the following are intervention exclusions: - known previous history of transfusion-related acute lung injury will exclude a patient from convalescent plasma; - known previous history of serious allergic reaction to blood product transfusion will exclude a patient from convalescent plasma; - known personal or religious objections to receiving blood products will exclude a patient from receiving convalescent plasma; d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - receiving dual antiplatelet therapy - the treating clinician intends to continue or commence therapeutic anticoagulation contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity - severe thrombocytopenia (platelet count less than 30 x 109/l) - history of intracranial haemorrhage in the previous 3 months - severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive thromboprophylaxis domain c (anticoagulation) intervention-level

a. overall platform exclusions: 1. currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. note, participants already on community based non-invasive ventilation (either cpap or bipap) can still be recruited. humidified high flow nasal oxygen will not be considered an exclusion criterion. 2. previous participation in the trial 3. treating team deems enrolment in the study is not in the best interests of the patient 4. death is deemed to be imminent and inevitable within the next 24 hours 5. either the patient or their primary treating clinician are not committed to active treatment. this criterion seeks to exclude those patients where supportive comfort measures only are being provided. patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included. b. domain a (antiviral) intervention-level exclusions: criteria that exclude a patient from one or more interventions are: nafamostat: - known current decompensated liver disease (child-pugh b or c) - the treating clinician intends to continue or commence therapeutic anticoagulation - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation - serum potassium >5.5 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - serum sodium <120 mmol/l (based on most recent blood test result collected as part of routine care within the previous 3 days) - hypersensitivity to nafamostat - pregnancy or breastfeeding - currently receiving or have received nafamostat in the past 7 days - decompensated heart failure or renal dialysis and clinician believes an extra 500ml fluid/day would be detrimental there are no domain-level exclusions for the antiviral domain. c. domain b (antibody) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - participant has already received treatment with sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment; - treating team deems enrolment in antibody intervention is not in the best interests of the patient. domain b (antibody) intervention-level exclusions: the following are intervention exclusions: - known previous history of transfusion-related acute lung injury will exclude a patient from convalescent plasma; - known previous history of serious allergic reaction to blood product transfusion will exclude a patient from convalescent plasma; - known personal or religious objections to receiving blood products will exclude a patient from receiving convalescent plasma; d. domain c (anticoagulation) domain-level exclusions: patients will be excluded from this domain if they have any of the following: - receiving dual antiplatelet therapy - the treating clinician intends to continue or commence therapeutic anticoagulation contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity - severe thrombocytopenia (platelet count less than 30 x 109/l) - history of intracranial haemorrhage in the previous 3 months - severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2 - a current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive thromboprophylaxis domain c (anticoagulation) intervention-level

a. overall exclusions: 1. currently receiving acute intensive respiratory support (invasive or noninvasive ventilation) or vasopressor/inotropic support. note, participants already on non-invasive ventilation (either cpap or bipap) in the community can still be recruited if they are continuing on their usual degree of niv. humidified high flow nasal oxygen will not be considered an exclusion criterion. 2. previous participation in the trial; 3. known pregnancy; 4. treating team deems enrolment in the study is not in the best interests of the patient; 5. death is deemed to be imminent and inevitable within the next 24 hours; 6. enrolment to other study protocols that do not allow co-enrolment in ascot. b. domain 1 (antiviral) specific exclusions: 1. lpv/r not available at trial site; 2. hydroxychloroquine not available at trial site; 3. currently taking lpv/r or hydroxychloroquine; 4. known allergy or hypersensitivity to lpv/r or hydroxychloroquine 5. use of medications that are contraindicated with lpv/r or hydroxychloroquine that cannot be replaced or stopped during the study period; 6. known cirrhosis or alt or ast > 5x upper limit of normal; 7. known hiv infection not on antiretroviral therapy; 8. qtc ≥470ms for males, qtc ≥480ms for females; 9. treating team deems enrolment in antiviral interventions is not in the best interests of the patient. c. domain 2 (convalescent plasma) specific exclusions: 1. convalescent plasma not available at trial site; 2. participant has already received treatment with non-trial prescribed sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody); 3. known previous history of transfusion-related acute lung injury; 4. know previous history of serious allergic reaction to blood product transfusion; 5. known religious objection to receiving blood products; 6. treating team deems enrolment in antibody interventions is not in the best interests of the patient.

a. overall exclusions: 1. currently receiving acute intensive respiratory support (invasive or noninvasive ventilation) or vasopressor/inotropic support. note, participants already on non-invasive ventilation (either cpap or bipap) in the community can still be recruited if they are continuing on their usual degree of niv. humidified high flow nasal oxygen will not be considered an exclusion criterion. 2. previous participation in the trial; 3. known pregnancy; 4. treating team deems enrolment in the study is not in the best interests of the patient; 5. death is deemed to be imminent and inevitable within the next 24 hours; 6. enrolment to other study protocols that do not allow co-enrolment in ascot. b. domain 1 (antiviral) specific exclusions: 1. lpv/r not available at trial site; 2. hydroxychloroquine not available at trial site; 3. currently taking lpv/r or hydroxychloroquine; 4. known allergy or hypersensitivity to lpv/r or hydroxychloroquine 5. use of medications that are contraindicated with lpv/r or hydroxychloroquine that cannot be replaced or stopped during the study period; 6. known cirrhosis or alt or ast > 5x upper limit of normal; 7. known hiv infection not on antiretroviral therapy; 8. qtc ≥470ms for males, qtc ≥480ms for females; 9. treating team deems enrolment in antiviral interventions is not in the best interests of the patient. c. domain 2 (convalescent plasma) specific exclusions: 1. convalescent plasma not available at trial site; 2. participant has already received treatment with non-trial prescribed sars-cov-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody); 3. known previous history of transfusion-related acute lung injury; 4. know previous history of serious allergic reaction to blood product transfusion; 5. known religious objection to receiving blood products; 6. treating team deems enrolment in antibody interventions is not in the best interests of the patient.