COVID-19 Related Medical Conditions <br/ >1. Respiratory failure at the time of screening due to COVID-19 pneumonia. <br/ >2. Known medical resuscitation within 14 days of randomization. <br/ >3. Any serious medical condition or abnormality of clinical laboratory tests that, in the Investigators judgment, precludes the subjects safe participation in and completion of the study <br/ >4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARSCoV2). <br/ >5. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments <br/ > <br/ >Medical Conditions <br/ >6. Not expected to survive 28 days given their pre-existing, uncorrectable medical condition. <br/ >7. Pregnant or breast feeding. <br/ >8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin � 3x upper limit of normal (ULN) and/or severe hepatic impairment (Child-Pugh class C). <br/ >9. Absolute neutrophil count (ANC) < 500/μL at screening (per local laboratory). <br/ >10. Platelet count < 50,000/μL at screening (per local laboratory). <br/ >11. Estimated creatinine clearance of <30 mL/min calculated using the Cockcroft-Gault formula [(140age) � mass (kg)/(72 � creatinine mg/dL) multiply by 0.85 if female]. <br/ >12.Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). <br/ >Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening area allowed to enrol on study. <br/ >13.History of chronic hypercarbia, respiratory failure in past 6 months, or use of home oxygen in the setting of severe chronic respiratory disease. <br/ >14.Quadriplegia. <br/ >15.History of primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy (PML), aspergillus or other invasive mold/fungal infection, or received organ or bone marrow transplantation within 6 months of randomization. <br/ >16.Known active hepatitis B or C infection requiring therapy. <br/ > <br/ >Prior/Concomitant Therapy: <br/ > <br/ >17.Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug). <br/ >18.Requires treatment with proton-pump inhibitors. <br/ >19.Received oral antirejection or immunomodulatory drugs. <br/ >20.Active participation in other drug clinical trials or received treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization/enrolment. <br/ >21.Subjects at randomization who require inhaled corticosteroids or maintenance doses of more than 7.5 mg of prednisone or equivalent per day. <br/ >22.Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of acalabrutinib. <br/ >23.History of hypersensitivity (ie, allergic response) to active or inactive excipients of acalabrutinib or other Btk inhibitors. <br/ >24.Known cytoreductive chemotherapy treatment within 14 days of randomization. <br/ >25.Major surgery (as defined by the Investigator) within 4 weeks prior to randomization or still recovering from prior surgery.

COVID-19 Related Medical Conditions <br/ >1. Respiratory failure at the time of screening due to COVID-19 pneumonia. <br/ >2. Known medical resuscitation within 14 days of randomization. <br/ >3. Any serious medical condition or abnormality of clinical laboratory tests that, in the Investigators judgment, precludes the subjects safe participation in and completion of the study <br/ >4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARSCoV2). <br/ >5. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments <br/ > <br/ >Medical Conditions <br/ >6. Not expected to survive 28 days given their pre-existing, uncorrectable medical condition. <br/ >7. Pregnant or breast feeding. <br/ >8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin � 3x upper limit of normal (ULN) and/or severe hepatic impairment (Child-Pugh class C). <br/ >9. Absolute neutrophil count (ANC) < 500/μL at screening (per local laboratory). <br/ >10. Platelet count < 50,000/μL at screening (per local laboratory). <br/ >11. Estimated creatinine clearance of <30 mL/min calculated using the Cockcroft-Gault formula [(140age) � mass (kg)/(72 � creatinine mg/dL) multiply by 0.85 if female]. <br/ >12.Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). <br/ >Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening area allowed to enrol on study. <br/ >13.History of chronic hypercarbia, respiratory failure in past 6 months, or use of home oxygen in the setting of severe chronic respiratory disease. <br/ >14.Quadriplegia. <br/ >15.History of primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy (PML), aspergillus or other invasive mold/fungal infection, or received organ or bone marrow transplantation within 6 months of randomization. <br/ >16.Known active hepatitis B or C infection requiring therapy. <br/ > <br/ >Prior/Concomitant Therapy: <br/ > <br/ >17.Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug). <br/ >18.Requires treatment with proton-pump inhibitors. <br/ >19.Received oral antirejection or immunomodulatory drugs. <br/ >20.Active participation in other drug clinical trials or received treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization/enrolment. <br/ >21.Subjects at randomization who require inhaled corticosteroids or maintenance doses of more than 7.5 mg of prednisone or equivalent per day. <br/ >22.Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of acalabrutinib. <br/ >23.History of hypersensitivity (ie, allergic response) to active or inactive excipients of acalabrutinib or other Btk inhibitors. <br/ >24.Known cytoreductive chemotherapy treatment within 14 days of randomization. <br/ >25.Major surgery (as defined by the Investigator) within 4 weeks prior to randomization or still recovering from prior surgery.

N/A

N/A

COVID-19 Related Medical Conditions <br/ >1. Respiratory failure at the time of screening due to COVID-19 pneumonia. <br/ >2. Known medical resuscitation within 14 days of randomization. <br/ >3. Any serious medical condition or abnormality of clinical laboratory tests that, in the Investigators judgment, precludes the subjects safe participation in and completion of the study <br/ >4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARSCoV2). <br/ >5. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments <br/ > <br/ >Medical Conditions <br/ >6. Not expected to survive 28 days given their pre-existing, uncorrectable medical condition. <br/ >7. Pregnant or breast feeding. <br/ >8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin � 3x upper limit of normal (ULN) and/or severe hepatic impairment (Child-Pugh class C). <br/ >9. Absolute neutrophil count (ANC) < 500/μL at screening (per local laboratory). <br/ >10. Platelet count < 50,000/μL at screening (per local laboratory). <br/ >11. Estimated creatinine clearance of <30 mL/min calculated using the Cockcroft-Gault formula [(140age) � mass (kg)/(72 � creatinine mg/dL) multiply by 0.85 if female]. <br/ >12.Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). <br/ >Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening area allowed to enrol on study. <br/ >13.History of chronic hypercarbia, respiratory failure in past 6 months, or use of home oxygen in the setting of severe chronic respiratory disease. <br/ >14.Quadriplegia. <br/ >15.History of primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy (PML), aspergillus or other invasive mold/fungal infection, or received organ or bone marrow transplantation within 6 months of randomization. <br/ >16.Known active hepatitis B or C infection requiring therapy. <br/ > <br/ >Prior/Concomitant Therapy: <br/ > <br/ >17.Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug). <br/ >18.Requires treatment with proton-pump inhibitors. <br/ >19.Received oral antirejection or immunomodulatory drugs. <br/ >20.Active participation in other drug clinical trials or received treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization/enrolment. <br/ >21.Subjects at randomization who require inhaled corticosteroids or maintenance doses of more than 7.5 mg of prednisone or equivalent per day. <br/ >22.Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of acalabrutinib. <br/ >23.History of hypersensitivity (ie, allergic response) to active or inactive excipients of acalabrutinib or other Btk inhibitors. <br/ >24.Known cytoreductive chemotherapy treatment within 14 days of randomization. <br/ >25.Major surgery (as defined by the Investigator) within 4 weeks prior to randomization or still recovering from prior surgery.

COVID-19 Related Medical Conditions <br/ >1. Respiratory failure at the time of screening due to COVID-19 pneumonia. <br/ >2. Known medical resuscitation within 14 days of randomization. <br/ >3. Any serious medical condition or abnormality of clinical laboratory tests that, in the Investigators judgment, precludes the subjects safe participation in and completion of the study <br/ >4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARSCoV2). <br/ >5. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments <br/ > <br/ >Medical Conditions <br/ >6. Not expected to survive 28 days given their pre-existing, uncorrectable medical condition. <br/ >7. Pregnant or breast feeding. <br/ >8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin � 3x upper limit of normal (ULN) and/or severe hepatic impairment (Child-Pugh class C). <br/ >9. Absolute neutrophil count (ANC) < 500/μL at screening (per local laboratory). <br/ >10. Platelet count < 50,000/μL at screening (per local laboratory). <br/ >11. Estimated creatinine clearance of <30 mL/min calculated using the Cockcroft-Gault formula [(140age) � mass (kg)/(72 � creatinine mg/dL) multiply by 0.85 if female]. <br/ >12.Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). <br/ >Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening area allowed to enrol on study. <br/ >13.History of chronic hypercarbia, respiratory failure in past 6 months, or use of home oxygen in the setting of severe chronic respiratory disease. <br/ >14.Quadriplegia. <br/ >15.History of primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy (PML), aspergillus or other invasive mold/fungal infection, or received organ or bone marrow transplantation within 6 months of randomization. <br/ >16.Known active hepatitis B or C infection requiring therapy. <br/ > <br/ >Prior/Concomitant Therapy: <br/ > <br/ >17.Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug). <br/ >18.Requires treatment with proton-pump inhibitors. <br/ >19.Received oral antirejection or immunomodulatory drugs. <br/ >20.Active participation in other drug clinical trials or received treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization/enrolment. <br/ >21.Subjects at randomization who require inhaled corticosteroids or maintenance doses of more than 7.5 mg of prednisone or equivalent per day. <br/ >22.Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of acalabrutinib. <br/ >23.History of hypersensitivity (ie, allergic response) to active or inactive excipients of acalabrutinib or other Btk inhibitors. <br/ >24.Known cytoreductive chemotherapy treatment within 14 days of randomization. <br/ >25.Major surgery (as defined by the Investigator) within 4 weeks prior to randomization or still recovering from prior surgery.