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

METHODS:

• 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  

RESULTS:

• 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

CONCLUSION:

• 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

Learn More – Primary Sources:

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19

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