1. patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥10l nasal cannula at screening 2. patients currently in shock as defined by hemodynamic instability requiring vasopressors 3. patients with a current hospitalization for covid-19 that is \>/=7 days at the time of screening. 4. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment 5. patients in which either symptom onset or a positive covid-19 laboratory test occurred \>14 days prior to enrollment. 6. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. 7. female patients who are pregnant or breastfeeding at time of hospital admission 8. diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) 9. crcl \< 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening 10. history of cirrhosis or advanced liver disease, or active hepatic viral infection 11. transplant of kidney, lung, heart, or liver in the past 2 years 12. uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months 13. patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl \< 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). 14. patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies 15. chronic or current use of colchicine or any mu-opioid antagonist. 16. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. 17. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. 18. note: patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for covid-19. use of tocilizumab at baseline for another indication will continue to be excluded. 19. participation in any other clinical trial of an experimental treatment for covid-19, note: 1. while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; 2. patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; 3. remdesivir is allowed per standard protocol; 4. dexamethasone is allowed per standard protocol 20. patients actively enrolled in hospice or that are dni or on palliative care 21. history of hypersensitivity reaction to colchicine or its inactive ingredients 22. history of hypersensitivity reaction to naltrexone or its inactive ingredients 23. incarcerated or a ward of the state 24. any patient considered an unsuitable candidate, for any reason, by study investigators.

1. patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥10l nasal cannula at screening 2. patients currently in shock as defined by hemodynamic instability requiring vasopressors 3. patients with a current hospitalization for covid-19 that is \>/=7 days at the time of screening. 4. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment 5. patients in which either symptom onset or a positive covid-19 laboratory test occurred \>14 days prior to enrollment. 6. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. 7. female patients who are pregnant or breastfeeding at time of hospital admission 8. diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) 9. crcl \< 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening 10. history of cirrhosis or advanced liver disease, or active hepatic viral infection 11. transplant of kidney, lung, heart, or liver in the past 2 years 12. uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months 13. patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl \< 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). 14. patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies 15. chronic or current use of colchicine or any mu-opioid antagonist. 16. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. 17. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. 18. note: patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for covid-19. use of tocilizumab at baseline for another indication will continue to be excluded. 19. participation in any other clinical trial of an experimental treatment for covid-19, note: 1. while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; 2. patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; 3. remdesivir is allowed per standard protocol; 4. dexamethasone is allowed per standard protocol 20. patients actively enrolled in hospice or that are dni or on palliative care 21. history of hypersensitivity reaction to colchicine or its inactive ingredients 22. history of hypersensitivity reaction to naltrexone or its inactive ingredients 23. incarcerated or a ward of the state 24. any patient considered an unsuitable candidate, for any reason, by study investigators.

patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥10l nasal cannula at screening patients currently in shock as defined by hemodynamic instability requiring vasopressors patients with a current hospitalization for covid-19 that is >/=7 days at the time of screening. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment patients in which either symptom onset or a positive covid-19 laboratory test occurred >14 days prior to enrollment. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. female patients who are pregnant or breastfeeding at time of hospital admission diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) crcl < 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening history of cirrhosis or advanced liver disease, or active hepatic viral infection transplant of kidney, lung, heart, or liver in the past 2 years uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl < 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies chronic or current use of colchicine or any mu-opioid antagonist. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. note: patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for covid-19. use of tocilizumab at baseline for another indication will continue to be excluded. participation in any other clinical trial of an experimental treatment for covid-19, note: while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; remdesivir is allowed per standard protocol; dexamethasone is allowed per standard protocol patients actively enrolled in hospice or that are dni or on palliative care history of hypersensitivity reaction to colchicine or its inactive ingredients history of hypersensitivity reaction to naltrexone or its inactive ingredients incarcerated or a ward of the state any patient considered an unsuitable candidate, for any reason, by study investigators.

patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥10l nasal cannula at screening patients currently in shock as defined by hemodynamic instability requiring vasopressors patients with a current hospitalization for covid-19 that is >/=7 days at the time of screening. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment patients in which either symptom onset or a positive covid-19 laboratory test occurred >14 days prior to enrollment. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. female patients who are pregnant or breastfeeding at time of hospital admission diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) crcl < 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening history of cirrhosis or advanced liver disease, or active hepatic viral infection transplant of kidney, lung, heart, or liver in the past 2 years uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl < 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies chronic or current use of colchicine or any mu-opioid antagonist. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. note: patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for covid-19. use of tocilizumab at baseline for another indication will continue to be excluded. participation in any other clinical trial of an experimental treatment for covid-19, note: while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; remdesivir is allowed per standard protocol; dexamethasone is allowed per standard protocol patients actively enrolled in hospice or that are dni or on palliative care history of hypersensitivity reaction to colchicine or its inactive ingredients history of hypersensitivity reaction to naltrexone or its inactive ingredients incarcerated or a ward of the state any patient considered an unsuitable candidate, for any reason, by study investigators.

1. patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥10l nasal cannula at screening 2. patients currently in shock as defined by hemodynamic instability requiring vasopressors 3. patients with a current hospitalization for covid-19 that is >/=7 days at the time of screening. 4. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment 5. patients in which either symptom onset or a positive covid-19 laboratory test occurred >14 days prior to enrollment. 6. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. 7. female patients who are pregnant or breastfeeding at time of hospital admission 8. diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) 9. crcl < 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening 10. history of cirrhosis or advanced liver disease, or active hepatic viral infection 11. transplant of kidney, lung, heart, or liver in the past 2 years 12. uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months 13. patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl < 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). 14. patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies 15. chronic or current use of colchicine or any mu-opioid antagonist. 16. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. 17. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. 18. note: patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for covid-19. use of tocilizumab at baseline for another indication will continue to be excluded. 19. participation in any other clinical trial of an experimental treatment for covid-19, note: 1. while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; 2. patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; 3. remdesivir is allowed per standard protocol; 4. dexamethasone is allowed per standard protocol 20. patients actively enrolled in hospice or that are dni or on palliative care 21. history of hypersensitivity reaction to colchicine or its inactive ingredients 22. history of hypersensitivity reaction to naltrexone or its inactive ingredients 23. incarcerated or a ward of the state 24. any patient considered an unsuitable candidate, for any reason, by study investigators.

1. patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥10l nasal cannula at screening 2. patients currently in shock as defined by hemodynamic instability requiring vasopressors 3. patients with a current hospitalization for covid-19 that is >/=7 days at the time of screening. 4. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment 5. patients in which either symptom onset or a positive covid-19 laboratory test occurred >14 days prior to enrollment. 6. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. 7. female patients who are pregnant or breastfeeding at time of hospital admission 8. diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) 9. crcl < 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening 10. history of cirrhosis or advanced liver disease, or active hepatic viral infection 11. transplant of kidney, lung, heart, or liver in the past 2 years 12. uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months 13. patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl < 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). 14. patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies 15. chronic or current use of colchicine or any mu-opioid antagonist. 16. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. 17. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. 18. note: patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for covid-19. use of tocilizumab at baseline for another indication will continue to be excluded. 19. participation in any other clinical trial of an experimental treatment for covid-19, note: 1. while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; 2. patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; 3. remdesivir is allowed per standard protocol; 4. dexamethasone is allowed per standard protocol 20. patients actively enrolled in hospice or that are dni or on palliative care 21. history of hypersensitivity reaction to colchicine or its inactive ingredients 22. history of hypersensitivity reaction to naltrexone or its inactive ingredients 23. incarcerated or a ward of the state 24. any patient considered an unsuitable candidate, for any reason, by study investigators.

1. patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥6l nasal cannula at screening 2. patients currently in shock as defined by hemodynamic instability requiring vasopressors 3. patients with a current hospitalization for covid-19 that is >/=7 days at the time of screening. 4. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment 5. clinical estimation of attending physician that patient will be discharged within 48 hours of enrollment 6. patients in which either symptom onset or a positive covid-19 laboratory test occurred >10 days prior to enrollment. 7. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. 8. female patients who are pregnant or breastfeeding at time of hospital admission 9. diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) 10. crcl < 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening 11. history of cirrhosis or advanced liver disease, or active hepatic viral infection 12. transplant of kidney, lung, heart, or liver in the past 2 years 13. uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months 14. patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl < 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). 15. patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies 16. chronic or current use of colchicine or any mu-opioid antagonist. 17. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. 18. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. 19. participation in any other clinical trial of an experimental treatment for covid-19, note: a. while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; b. patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; c.remdesivir is allowed per standard protocol; d. dexamethasone is allowed per standard protocol 20. patients actively enrolled in hospice or that are dni or on palliative care 21. history of hypersensitivity reaction to colchicine or its inactive ingredients 22. history of hypersensitivity reaction to naltrexone or its inactive ingredients 23. incarcerated or a ward of the state 24. any patient considered an unsuitable candidate, for any reason, by study investigators.

1. patients meeting criteria for severe/critical covid-19 as defined by study protocol or requiring o2 supplementation ≥6l nasal cannula at screening 2. patients currently in shock as defined by hemodynamic instability requiring vasopressors 3. patients with a current hospitalization for covid-19 that is >/=7 days at the time of screening. 4. clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment 5. clinical estimation of attending physician that patient will be discharged within 48 hours of enrollment 6. patients in which either symptom onset or a positive covid-19 laboratory test occurred >10 days prior to enrollment. 7. patients with concomitant influenza a or b at time of hospitalization if tested as part of ed/hospital admission. 8. female patients who are pregnant or breastfeeding at time of hospital admission 9. diagnosis of chronic kidney disease stage ≥4 as documented in the patient's problem list (not based on crci calculations alone) 10. crcl < 30 ml/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening 11. history of cirrhosis or advanced liver disease, or active hepatic viral infection 12. transplant of kidney, lung, heart, or liver in the past 2 years 13. uncontrolled severe gastrointestinal disorders, crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months 14. patients currently receiving agents that are p-glycoprotein and strong cyp3a4 inhibitors with crcl < 60 ml/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential colchicine and naltrexone interactions). 15. patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies 16. chronic or current use of colchicine or any mu-opioid antagonist. 17. chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. 18. pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, tnf-inhibitors, or jak inhibitors. 19. participation in any other clinical trial of an experimental treatment for covid-19, note: a. while convalescent plasma is no longer recommended within hp, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; b. patients previously enrolled in the c3po study can enroll in this study, as any convalescent plasma received would have been outpatient; c.remdesivir is allowed per standard protocol; d. dexamethasone is allowed per standard protocol 20. patients actively enrolled in hospice or that are dni or on palliative care 21. history of hypersensitivity reaction to colchicine or its inactive ingredients 22. history of hypersensitivity reaction to naltrexone or its inactive ingredients 23. incarcerated or a ward of the state 24. any patient considered an unsuitable candidate, for any reason, by study investigators.