1. is hospitalized for covid-19; 2. has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure; 3. has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; new york heart association class 3 or 4 congestive heart failure; ≥grade 3 hypertension (diastolic blood pressure ≥100 mmhg or systolic blood pressure ≥160 mmhg); or history of congenital prolonged qt syndrome; 4. has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; note: intermittent use of a β2-agonist inhaler is allowed. 5. has evidence of an ongoing or systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) other than sars-cov-2 infection, recurrent or repeat sars cov 2 infection, or history of incompletely treated tuberculosis (tb) and/or suspected or known extrapulmonary tb; note: patients with localized fungal infections of the skin or nails are eligible. patients may be receiving topical antifungals. systemic administration of azole antifungals is prohibited (see section 5.6). 6. has significant infiltrates (involving \>50% of lung parenchyma) on an optional standard of care chest x-ray or other lung imaging exam within 1 week of screening; 7. has known significant electrocardiogram abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (av) block type ii, third-degree av block, ≥grade 2 bradycardia, or qtcf \>450 msec for men or \>470 msec for women; 8. has type 1 diabetes mellitus or type 2 diabetes mellitus; 9. has a body mass index (bmi) \>30 kg/m2; 10. has received a live vaccine within 30 days prior to randomization; 11. has had major surgery within 4 weeks (inclusive) prior to randomization; 12. has had prior solid organ or bone marrow progenitor cell transplantation; 13. has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type); 14. has had prior high-dose chemotherapy requiring stem cell rescue; 15. has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system; 16. has ongoing immunosuppressive therapy, including systemic corticosteroids; note: at screening and during study participation, patients may be using systemic corticosteroids (doses ≤10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. 17. has ongoing use of a therapeutic anticoagulant or history of bleeding disorder; 18. has ongoing use or plans to use antivirals against covid-19; 19. has used a moderate or strong inhibitor or inducer of cyp3a4 within 7 days prior to randomization or is expected to require use of a moderate or strong cyp3a4 inhibitor or inducer during study participation; 20. has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study; note: participation in observational studies is allowed. 21. has a known history of hiv or hepatitis b virus, or active hepatitis c virus infection; 22. has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo; 23. has a history of drug abuse or use of narcotics in the past 2 years that in the opinion of the investigator will preclude study compliance; or 24. has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to provide informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.

1. is hospitalized for covid-19; 2. has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure; 3. has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; new york heart association class 3 or 4 congestive heart failure; ≥grade 3 hypertension (diastolic blood pressure ≥100 mmhg or systolic blood pressure ≥160 mmhg); or history of congenital prolonged qt syndrome; 4. has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; note: intermittent use of a β2-agonist inhaler is allowed. 5. has evidence of an ongoing or systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) other than sars-cov-2 infection, recurrent or repeat sars cov 2 infection, or history of incompletely treated tuberculosis (tb) and/or suspected or known extrapulmonary tb; note: patients with localized fungal infections of the skin or nails are eligible. patients may be receiving topical antifungals. systemic administration of azole antifungals is prohibited (see section 5.6). 6. has significant infiltrates (involving \>50% of lung parenchyma) on an optional standard of care chest x-ray or other lung imaging exam within 1 week of screening; 7. has known significant electrocardiogram abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (av) block type ii, third-degree av block, ≥grade 2 bradycardia, or qtcf \>450 msec for men or \>470 msec for women; 8. has type 1 diabetes mellitus or type 2 diabetes mellitus; 9. has a body mass index (bmi) \>30 kg/m2; 10. has received a live vaccine within 30 days prior to randomization; 11. has had major surgery within 4 weeks (inclusive) prior to randomization; 12. has had prior solid organ or bone marrow progenitor cell transplantation; 13. has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type); 14. has had prior high-dose chemotherapy requiring stem cell rescue; 15. has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system; 16. has ongoing immunosuppressive therapy, including systemic corticosteroids; note: at screening and during study participation, patients may be using systemic corticosteroids (doses ≤10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. 17. has ongoing use of a therapeutic anticoagulant or history of bleeding disorder; 18. has ongoing use or plans to use antivirals against covid-19; 19. has used a moderate or strong inhibitor or inducer of cyp3a4 within 7 days prior to randomization or is expected to require use of a moderate or strong cyp3a4 inhibitor or inducer during study participation; 20. has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study; note: participation in observational studies is allowed. 21. has a known history of hiv or hepatitis b virus, or active hepatitis c virus infection; 22. has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo; 23. has a history of drug abuse or use of narcotics in the past 2 years that in the opinion of the investigator will preclude study compliance; or 24. has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to provide informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.

is hospitalized for covid-19; has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure; has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; new york heart association class 3 or 4 congestive heart failure; ≥grade 3 hypertension (diastolic blood pressure ≥100 mmhg or systolic blood pressure ≥160 mmhg); or history of congenital prolonged qt syndrome; has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; note: intermittent use of a β2-agonist inhaler is allowed. has evidence of an ongoing or systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) other than sars-cov-2 infection, recurrent or repeat sars cov 2 infection, or history of incompletely treated tuberculosis (tb) and/or suspected or known extrapulmonary tb; note: patients with localized fungal infections of the skin or nails are eligible. patients may be receiving topical antifungals. systemic administration of azole antifungals is prohibited (see section 5.6). has significant infiltrates (involving >50% of lung parenchyma) on an optional standard of care chest x-ray or other lung imaging exam within 1 week of screening; has known significant electrocardiogram abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (av) block type ii, third-degree av block, ≥grade 2 bradycardia, or qtcf >450 msec for men or >470 msec for women; has type 1 diabetes mellitus or type 2 diabetes mellitus; has a body mass index (bmi) >30 kg/m2; has received a live vaccine within 30 days prior to randomization; has had major surgery within 4 weeks (inclusive) prior to randomization; has had prior solid organ or bone marrow progenitor cell transplantation; has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type); has had prior high-dose chemotherapy requiring stem cell rescue; has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system; has ongoing immunosuppressive therapy, including systemic corticosteroids; note: at screening and during study participation, patients may be using systemic corticosteroids (doses ≤10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. has ongoing use of a therapeutic anticoagulant or history of bleeding disorder; has ongoing use or plans to use antivirals against covid-19; has used a moderate or strong inhibitor or inducer of cyp3a4 within 7 days prior to randomization or is expected to require use of a moderate or strong cyp3a4 inhibitor or inducer during study participation; has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study; note: participation in observational studies is allowed. has a known history of hiv or hepatitis b virus, or active hepatitis c virus infection; has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo; has a history of drug abuse or use of narcotics in the past 2 years that in the opinion of the investigator will preclude study compliance; or has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to provide informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.

is hospitalized for covid-19; has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure; has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; new york heart association class 3 or 4 congestive heart failure; ≥grade 3 hypertension (diastolic blood pressure ≥100 mmhg or systolic blood pressure ≥160 mmhg); or history of congenital prolonged qt syndrome; has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; note: intermittent use of a β2-agonist inhaler is allowed. has evidence of an ongoing or systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) other than sars-cov-2 infection, recurrent or repeat sars cov 2 infection, or history of incompletely treated tuberculosis (tb) and/or suspected or known extrapulmonary tb; note: patients with localized fungal infections of the skin or nails are eligible. patients may be receiving topical antifungals. systemic administration of azole antifungals is prohibited (see section 5.6). has significant infiltrates (involving >50% of lung parenchyma) on an optional standard of care chest x-ray or other lung imaging exam within 1 week of screening; has known significant electrocardiogram abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (av) block type ii, third-degree av block, ≥grade 2 bradycardia, or qtcf >450 msec for men or >470 msec for women; has type 1 diabetes mellitus or type 2 diabetes mellitus; has a body mass index (bmi) >30 kg/m2; has received a live vaccine within 30 days prior to randomization; has had major surgery within 4 weeks (inclusive) prior to randomization; has had prior solid organ or bone marrow progenitor cell transplantation; has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type); has had prior high-dose chemotherapy requiring stem cell rescue; has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system; has ongoing immunosuppressive therapy, including systemic corticosteroids; note: at screening and during study participation, patients may be using systemic corticosteroids (doses ≤10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. has ongoing use of a therapeutic anticoagulant or history of bleeding disorder; has ongoing use or plans to use antivirals against covid-19; has used a moderate or strong inhibitor or inducer of cyp3a4 within 7 days prior to randomization or is expected to require use of a moderate or strong cyp3a4 inhibitor or inducer during study participation; has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study; note: participation in observational studies is allowed. has a known history of hiv or hepatitis b virus, or active hepatitis c virus infection; has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo; has a history of drug abuse or use of narcotics in the past 2 years that in the opinion of the investigator will preclude study compliance; or has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to provide informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.

1. is hospitalized for covid-19; 2. has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure; 3. has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; new york heart association class 3 or 4 congestive heart failure; ≥grade 3 hypertension (diastolic blood pressure ≥100 mmhg or systolic blood pressure ≥160 mmhg); or history of congenital prolonged qt syndrome; 4. has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; note: intermittent use of a β2-agonist inhaler is allowed. 5. has evidence of an ongoing or systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) other than sars-cov-2 infection, recurrent or repeat sars cov 2 infection, or history of incompletely treated tuberculosis (tb) and/or suspected or known extrapulmonary tb; note: patients with localized fungal infections of the skin or nails are eligible. patients may be receiving topical antifungals. systemic administration of azole antifungals is prohibited (see section 5.6). 6. has significant infiltrates (involving >50% of lung parenchyma) on an optional standard of care chest x-ray or other lung imaging exam within 1 week of screening; 7. has known significant electrocardiogram abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (av) block type ii, third-degree av block, ≥grade 2 bradycardia, or qtcf >450 msec for men or >470 msec for women; 8. has type 1 diabetes mellitus or type 2 diabetes mellitus; 9. has a body mass index (bmi) >30 kg/m2; 10. has received a live vaccine within 30 days prior to randomization; 11. has had major surgery within 4 weeks (inclusive) prior to randomization; 12. has had prior solid organ or bone marrow progenitor cell transplantation; 13. has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type); 14. has had prior high-dose chemotherapy requiring stem cell rescue; 15. has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system; 16. has ongoing immunosuppressive therapy, including systemic corticosteroids; note: at screening and during study participation, patients may be using systemic corticosteroids (doses ≤10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. 17. has ongoing use of a therapeutic anticoagulant or history of bleeding disorder; 18. has ongoing use or plans to use antivirals against covid-19; 19. has used a moderate or strong inhibitor or inducer of cyp3a4 within 7 days prior to randomization or is expected to require use of a moderate or strong cyp3a4 inhibitor or inducer during study participation; 20. has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study; note: participation in observational studies is allowed. 21. has a known history of hiv or hepatitis b virus, or active hepatitis c virus infection; 22. has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo; 23. has a history of drug abuse or use of narcotics in the past 2 years that in the opinion of the investigator will preclude study compliance; or 24. has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to provide informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.

1. is hospitalized for covid-19; 2. has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure; 3. has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; new york heart association class 3 or 4 congestive heart failure; ≥grade 3 hypertension (diastolic blood pressure ≥100 mmhg or systolic blood pressure ≥160 mmhg); or history of congenital prolonged qt syndrome; 4. has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; note: intermittent use of a β2-agonist inhaler is allowed. 5. has evidence of an ongoing or systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) other than sars-cov-2 infection, recurrent or repeat sars cov 2 infection, or history of incompletely treated tuberculosis (tb) and/or suspected or known extrapulmonary tb; note: patients with localized fungal infections of the skin or nails are eligible. patients may be receiving topical antifungals. systemic administration of azole antifungals is prohibited (see section 5.6). 6. has significant infiltrates (involving >50% of lung parenchyma) on an optional standard of care chest x-ray or other lung imaging exam within 1 week of screening; 7. has known significant electrocardiogram abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (av) block type ii, third-degree av block, ≥grade 2 bradycardia, or qtcf >450 msec for men or >470 msec for women; 8. has type 1 diabetes mellitus or type 2 diabetes mellitus; 9. has a body mass index (bmi) >30 kg/m2; 10. has received a live vaccine within 30 days prior to randomization; 11. has had major surgery within 4 weeks (inclusive) prior to randomization; 12. has had prior solid organ or bone marrow progenitor cell transplantation; 13. has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type); 14. has had prior high-dose chemotherapy requiring stem cell rescue; 15. has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system; 16. has ongoing immunosuppressive therapy, including systemic corticosteroids; note: at screening and during study participation, patients may be using systemic corticosteroids (doses ≤10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. 17. has ongoing use of a therapeutic anticoagulant or history of bleeding disorder; 18. has ongoing use or plans to use antivirals against covid-19; 19. has used a moderate or strong inhibitor or inducer of cyp3a4 within 7 days prior to randomization or is expected to require use of a moderate or strong cyp3a4 inhibitor or inducer during study participation; 20. has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study; note: participation in observational studies is allowed. 21. has a known history of hiv or hepatitis b virus, or active hepatitis c virus infection; 22. has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo; 23. has a history of drug abuse or use of narcotics in the past 2 years that in the opinion of the investigator will preclude study compliance; or 24. has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to provide informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.