Table 2.
Outcomes and Adverse Events
| Outcome | COVID-19 Convalescent Plasma (n = 487) | Placebo (n = 473) | aOR, OR, or Adjusted Hazard Ratio (1/7 SI)a | Unadjusted Difference In Percentage Points (1/7 SI) |
|---|---|---|---|---|
| Primary efficacy outcome | ||||
| COVID Clinical Progression Ordinal Scale at 14 d, median (IQR)b | 2 (1-5) | 2 (1-4) | 1.04 (0.82 to 1.33) | |
| Secondary efficacy outcomes | ||||
| All-cause, all-location death, No. (%) | ||||
| At 14 d | 63/482 (13.1) | 48/465 (10.3) | 1.30 (0.79 to 2.12) | 2.7 (–1.4 to 6.9) |
| At 28 d | 89/482 (18.5) | 80/465 (17.2) | 1.04 (0.69 to 1.58) | 1.3 (–3.6 to 6.2) |
| Time to death through 28 d | 1.21 (0.88 to 1.64) | |||
| Time to hospital discharge | 1.00 (0.86 to 1.16) | |||
| Time to recovery (earlier of final receipt of oxygen or hospital discharge) | 1.00 (0.88 to 1.14) | |||
| COVID Clinical Progression Scale, median (IQR)b | ||||
| At 2 d | 4 (4-5) | 4 (4-5) | 1.26 (0.98 to 1.63) | |
| At 7 d | 3 (2-5) | 3 (2-5) | 1.12 (0.88 to 1.41) | |
| At 28 d | 2 (1-4) | 2 (1-4) | 1.19 (0.92 to 1.53) | |
| Support-free days through day 28, median (IQR) | ||||
| Hospital-free days | 20 (0-24) | 21 (0-24) | 0.98 (0.77 to 1.24) | |
| Oxygen-free days | 21 (0-25) | 21 (0-25) | 0.95 (0.75 to 1.21) | |
| ICU-free days | 28 (2-28) | 28 (13-28) | 0.92 (0.68 to 1.23) | |
| Ventilator-free days | 28 (18-28) | 28 (22-28) | 0.87 (0.61 to 1.24) | |
| Vasopressor-free days | 28 (27-28) | 28 (26-28) | 1.11 (0.78 to 1.60) | |
| Safety outcomes and adverse events, No. (%) | ||||
| Transfusion reaction | 6 (1.2) | 0 (0) | 1.2 (0.4 to 2.5) | |
| ≥ 1 Adverse event | 47 (9.7) | 33 (7.0) | 1.42 (0.86 to 2.27) | 2.7 (–0.8 to 6.2) |
| ≥ 1 Serious adverse event | 21 (4.3) | 16 (3.4) | 1.29 (0.66 to 2.51) | 0.9 (–1.5 to 3.4) |
1/7 SI = one-seventh support interval; aOR = adjusted OR; IQR = interquartile range.
Models for the primary and secondary efficacy outcomes were constructed with trial group assignment (COVID-19 convalescent plasma vs placebo) as the independent variable, the outcome as the dependent variable, and the following co-variates: age (as a restricted cubic spline with three knots), sex, Sequential Organ Failure Assessment score, baseline COVID-19 Clinical Progression Scale category (as a second degree polynomial), duration of COVID-19 symptoms (as a restricted cubic spline with three knots), and enrolling site (as a random effect). Multivariable cumulative probability ordinal regression models with logit link were used to analyze ordinal outcomes (COVID-19 Clinical Progression Scale outcomes and support-free outcomes). Multivariable logistic regression models were used for binary outcomes (binary death outcomes). Multivariable proportional hazards (Cox) models were used for time to event outcomes (time to death through 28 days, time to hospital discharge, and time to recovery). Discharge and recovery were potentially censored by death. Logistic regression models without covariate adjustment were used for safety outcomes and adverse events. ORs < 1.0 indicated more favorable outcomes for patients in the convalescent plasma group compared with the placebo group for the following outcomes: COVID Clinical Progression Scale (aOR < 1.0 indicated lower score on the scale); death (aOR < 1.0 indicated fewer deaths); transfusion reaction (aOR < 1.0 indicated fewer transfusion reactions); and adverse events (aOR < 1.0 indicated fewer adverse events). ORs > 1.0 indicate more favorable outcomes for patients in the convalescent plasma group compared with the placebo group for the support-free outcomes (aOR > 1.0 indicated more support free days). Variability for each OR was represented by a 1/7 SI.
The COVID Clinical Progression Scale is a seven-category ordinal scale that classifies a patient’s clinical status.22 The seven categories are: (1) not hospitalized with resumption of normal pre-illness activities; (2) not hospitalized but unable to resume normal pre-illness activities (including use of home supplemental oxygen by patients who did not use home oxygen pre-illness); (3) hospitalized and not on supplemental oxygen; (4) hospitalized and on standard flow supplemental oxygen; (5) hospitalized and on nasal high-flow oxygen therapy or noninvasive mechanical ventilation; (6) hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation; and (7) death.