Science, is what it is:
Works: Tocilizumab, (IL-6 monoclonal antibody), Dexamethasone, Remdesivir
Doesn't work: Hydroxychloroquine, convalescent plasma, Ivermectin
In addition, Remdesivir has also been show to lower mortality in moderate to severe cases by roughly 6%.
In patients hospitalized with COVID-19, hypoxemia, and systemic inflammation, treatment with tocilizumab was associated with a reduced 28-day mortality. Tocilizumab, an anti-IL-6 receptor monoclonal antibody, inhibits binding of IL-6 to its receptors, thereby blocking IL-6 signaling and decreasing inflammation. Early in the COVID-19 pandemic, it became evident that some patients with COVID-19 developed an acute hyperinflammatory syndrome characterized by elevations in proinflammatory cytokines and multiorgan failure. Although data were lacking, tocilizumab was used with the intent to mitigate this hyperinflammatory syndrome.
There have now been several randomized controlled trials (RCTs) investigating the role of tocilizumab in the treatment of COVID-19. Two of these RCTs, RECOVERY and REMAP-CAP, reported improved outcomes with tocilizumab in patients who were critically ill. Both trials permitted patients to be receiving mechanical ventilation at time of random assignment, and both initiated tocilizumab early in the hospital and ICU course. Taken together, these studies suggest that tocilizumab may be of greatest benefit when administered early and in patients with an inflammatory phenotype and rapidly progressive disease.
RECOVERY, the largest of these RCTs, enrolled 4,116 adults with hypoxia and evidence of systemic inflammation, defined by a C-reactive protein level ≥7.5 mg/dL (75 mg/L). Of the 2,022 adults randomly assigned to tocilizumab, 268 were receiving invasive mechanical ventilation and 819 were receiving noninvasive mechanical ventilation (high-flow nasal cannula, CPAP) at the time of random assignment. Glucocorticoid use was equal across both arms of the trial, with 82% of participants receiving dexamethasone, after data demonstrated it reduced mortality in COVID-19. Treatment with tocilizumab was associated with decreased 28-day mortality (31% vs 35%; RR, 0.85; 95% CI, 0.76-0.94; P = .0028). These findings were consistent in prespecified subgroup analysis, including those receiving glucocorticoids (29% vs 35%; RR, 0.79; 95% CI, 0.70-0.89), invasive mechanical ventilation at the time of random assignment (49% vs 51%; RR, 0.93; 95% CI, 0.74-1.18), and noninvasive mechanical ventilation (38% vs 42%; RR, 0.86; 95% CI, 0.74-1.00) (choice D is correct).
Patients critically ill with COVID-19 are at increased risk for thrombosis even when treated with standard-dose pharmacologic thromboprophylaxis. Furthermore, elevated biomarkers of thrombosis, such as D-dimer, are independently associated with greater risk of thrombosis, disease progression, and higher mortality in patients with COVID-19. However, therapeutic-dose anticoagulation with heparin has not been shown to decrease mortality in patients critically ill with COVID-19 (choice C is incorrect). An adaptive, multiplatform RCT in patients critically ill with COVID-19 randomly assigned 534 patients to therapeutic-dose anticoagulation and 564 patients to thromboprophylaxis (REMAP-CAP, ACTIV-4a, and ATTACC trials). Patients included in this trial required ICU-level respiratory or cardiovascular support, including high-flow nasal cannula, noninvasive or invasive mechanical ventilation, extracorporeal life support, vasopressors, or inotropes. In this trial, treatment with therapeutic-dose anticoagulation did not decrease in-hospital mortality, and results suggest probable harm with its use. Thus, empiric therapeutic-dose anticoagulation is not recommended in patients critically ill with COVID-19.
Neither convalescent plasma nor hydroxychloroquine has been shown to reduce mortality in patients hospitalized with COVID-19 (choices A and B are incorrect). RCTs of hydroxychloroquine showed a trend toward increased mortality in patients hospitalized with COVID-19 (RR, 1.08; 95% CI, 0.99-1.19).
Works: Tocilizumab, (IL-6 monoclonal antibody), Dexamethasone, Remdesivir
Doesn't work: Hydroxychloroquine, convalescent plasma, Ivermectin
In addition, Remdesivir has also been show to lower mortality in moderate to severe cases by roughly 6%.
In patients hospitalized with COVID-19, hypoxemia, and systemic inflammation, treatment with tocilizumab was associated with a reduced 28-day mortality. Tocilizumab, an anti-IL-6 receptor monoclonal antibody, inhibits binding of IL-6 to its receptors, thereby blocking IL-6 signaling and decreasing inflammation. Early in the COVID-19 pandemic, it became evident that some patients with COVID-19 developed an acute hyperinflammatory syndrome characterized by elevations in proinflammatory cytokines and multiorgan failure. Although data were lacking, tocilizumab was used with the intent to mitigate this hyperinflammatory syndrome.
There have now been several randomized controlled trials (RCTs) investigating the role of tocilizumab in the treatment of COVID-19. Two of these RCTs, RECOVERY and REMAP-CAP, reported improved outcomes with tocilizumab in patients who were critically ill. Both trials permitted patients to be receiving mechanical ventilation at time of random assignment, and both initiated tocilizumab early in the hospital and ICU course. Taken together, these studies suggest that tocilizumab may be of greatest benefit when administered early and in patients with an inflammatory phenotype and rapidly progressive disease.
RECOVERY, the largest of these RCTs, enrolled 4,116 adults with hypoxia and evidence of systemic inflammation, defined by a C-reactive protein level ≥7.5 mg/dL (75 mg/L). Of the 2,022 adults randomly assigned to tocilizumab, 268 were receiving invasive mechanical ventilation and 819 were receiving noninvasive mechanical ventilation (high-flow nasal cannula, CPAP) at the time of random assignment. Glucocorticoid use was equal across both arms of the trial, with 82% of participants receiving dexamethasone, after data demonstrated it reduced mortality in COVID-19. Treatment with tocilizumab was associated with decreased 28-day mortality (31% vs 35%; RR, 0.85; 95% CI, 0.76-0.94; P = .0028). These findings were consistent in prespecified subgroup analysis, including those receiving glucocorticoids (29% vs 35%; RR, 0.79; 95% CI, 0.70-0.89), invasive mechanical ventilation at the time of random assignment (49% vs 51%; RR, 0.93; 95% CI, 0.74-1.18), and noninvasive mechanical ventilation (38% vs 42%; RR, 0.86; 95% CI, 0.74-1.00) (choice D is correct).
Patients critically ill with COVID-19 are at increased risk for thrombosis even when treated with standard-dose pharmacologic thromboprophylaxis. Furthermore, elevated biomarkers of thrombosis, such as D-dimer, are independently associated with greater risk of thrombosis, disease progression, and higher mortality in patients with COVID-19. However, therapeutic-dose anticoagulation with heparin has not been shown to decrease mortality in patients critically ill with COVID-19 (choice C is incorrect). An adaptive, multiplatform RCT in patients critically ill with COVID-19 randomly assigned 534 patients to therapeutic-dose anticoagulation and 564 patients to thromboprophylaxis (REMAP-CAP, ACTIV-4a, and ATTACC trials). Patients included in this trial required ICU-level respiratory or cardiovascular support, including high-flow nasal cannula, noninvasive or invasive mechanical ventilation, extracorporeal life support, vasopressors, or inotropes. In this trial, treatment with therapeutic-dose anticoagulation did not decrease in-hospital mortality, and results suggest probable harm with its use. Thus, empiric therapeutic-dose anticoagulation is not recommended in patients critically ill with COVID-19.
Neither convalescent plasma nor hydroxychloroquine has been shown to reduce mortality in patients hospitalized with COVID-19 (choices A and B are incorrect). RCTs of hydroxychloroquine showed a trend toward increased mortality in patients hospitalized with COVID-19 (RR, 1.08; 95% CI, 0.99-1.19).
