COVID-19 Management

RCT Results: Convalescent Plasma for the Treatment of COVID-19

PURPOSE:

Li et al. (JAMA, 2020) assessed the efficacy of convalescent plasma therapy for the treatment of patients with severe or life-threatening COVID-19

Open-label, multicenter, randomized clinical trial (February 14 to April 1, 2020)
- 7 centers in Wuhan, China
Participants
- Laboratory-confirmed COVID-19
  - Severe: Respiratory distress and/or hypoxemia or
  - Life-threatening: Shock | Organ failure | Mechanical ventilation
Randomization (1:1)
- Intervention group: Standard treatment and convalescent plasma transfusion
- Control: Standard treatment alone
Convalescent plasma transfusion protocol
- Dose: 4 to 13 mL/kg | ABO type compatible
- Transfused at approximately 10 mL for the first 15 minutes and then increased to approximately 100 mL/hour
Primary outcome
- Clinical improvement within 28 days
- Determined using a 6 point disease severity scale | Improvement defined as a 2 point reduction
Secondary outcomes included
- 28-day mortality | Duration of hospitalization | Time from admission to discharge and 28-day discharge rates | Conversion of nasopharyngeal viral PCR results (positive to negative)
Statistical analysis
- 2-sided significance level of α = .05 | 80% power
- Would require 100 in each group to detect an 8 day change

103 patients randomized
- Median age: 70 years | Male 58.3%
- Median time from symptom onset to randomization: 30 days

Primary Outcome: Overall Clinical Improvement at 28 days

Overall
- Clinical improvement was greater in the convalescent plasma group (51.9%) vs control group (43.1%) but was not statistically significant
- Hazard ratio (HR): 1.40 (95% CI, 0.79 to 2.49; P = .26)
In the severe disease subgroup
- Clinical improvement was greater in the convalescent plasma group (91.3%) vs control group (68.2%) and this difference was statistically significant
- HR: 2.15 (95% CI, 1.07 to 4.32; P = .03)
In the life-threatening disease subgroup
- Clinical improvement was decreased (20.7%) vs the control group (24.1%) but this difference was not statistically significant
- HR: 0.88 (95% CI, 0.30 to 2.63; P = .83)
No differences were found for the following
- 28-day mortality
- Time from randomization to discharge
Conversion rates from a positive to a negative SARS-CoV-2 test (at 72 hours) was higher in the convalescent plasma group (87.2%) vs control group (37.5%)
- Odds ratio (OR): 11.39 (95% CI, 3.91 to 33.18; P < .001)
- Likewise, conversion rates were higher in the convalescent plasma group at 24 and 48 hours
2 adverse events (both patients improved with supportive care)
- 1 patient developed chills and rash (nonsevere allergic transfusion)
- 1 patient had severe transfusion-associated dyspnea

While overall, convalescent plasma therapy did not improve clinical course of patients with severe or life-threatening COVID-19, there may be benefit in the severe subset of patients
The association with higher conversion rates (from positive to negative test results) would support the hypothesis that convalescent plasma does have antiviral activity in these patients
Authors acknowledge study limitations
- Study was stopped early due to COVID-19 containment in Wuhan and insufficient cases to continue recruitment and therefore may have been underpowered
- Patients received therapy approximately a month (median value) after symptom onset and therefore unclear if earlier intervention would result in greater benefit

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