Skip to main content
U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Https

Secure .gov websites use HTTPS
A lock () or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Table 3b. COVID-19 Convalescent Plasma: Selected Clinical Data

Last Updated: December 16, 2021

The clinical trials described in this table do not represent all the trials that the Panel reviewed while developing the recommendations for COVID-19 CP. The studies summarized below are those that have had the greatest impact on the Panel’s recommendations.

Note: The current EUA for COVID-19 CP is limited to the use of high-titer CP. Refer to the revised EUA Letter of Authorization for a list of anti-SARS-CoV-2 antibody tests that can be used to qualify COVID-19 CP as high titer.

Table 3b. COVID-19 Convalescent Plasma: Selected Clinical Data
Methods Results Limitations and Interpretation
REMAP-CAP: Multinational, Open-Label RCT of High-Titer Convalescent Plasma in Hospitalized Patients With Critical COVID-191
Key Inclusion Criteria:
  • Admitted to ICU with receipt of respiratory support (HFNC oxygen, NIV, MV, ECMO) and/or vasopressor or inotrope support

Key Exclusion Criteria:

  • CP contraindicated
  • Death imminent

Interventions:

  • High-titer CP (550 mL +/- 150 mL) within 48 hours of randomization (n = 1,084)
  • Usual care (n = 916)

Primary Endpoint:

  • Organ support-free days by Day 21

Key Secondary Endpoints:

  • Mortality at Day 28 and Day 90
  • Progression to respiratory support
  • ICU LOS

Participant Characteristics:

  • Mean age 61 years; 68% men
  • 32% on MV
  • 29% SARS-CoV-2 antibody negative at baseline
  • 94% received corticosteroids, 45% received RDV, 39% received IL-6 inhibitors

Primary Outcome:

  • No difference in median number of organ support-free days by Day 21: 0 days in CP arm vs. 3 days in usual care arm (OR 0.97; 95% CrI, 0.82–1.14).

Secondary Outcomes:

  • No difference for in-hospital mortality between CP arm (37%) and usual care arm (38%).
  • No difference in median number of respiratory support-free days: 0 days in CP arm and 2 days in usual care arm.
  • No difference in median ICU LOS: 21 days in CP arm and 17 days in usual care arm.
Key Limitations:
  • Open-label study
  • Not all patients in CP arm received CP (86% received CP as per protocol and 95% received some CP)

Interpretation:

  • There was no benefit of CP in hospitalized patients with severe COVID-19.
CONCOR-1: Multinational, Open-Label RCT of Convalescent Plasma for Hospitalized Patients With COVID-19 in Canada, the United States, and Brazil2
Key Inclusion Criteria:
  • Hospitalized patients receiving supplemental oxygen
  • Within 12 days of respiratory symptom onset

Key Exclusion Criteria:

  • Imminent or current intubation

Interventions:

  • 1–2 units CP (approximately 500 mL) from 1–2 donors (n = 625)
  • SOC (n = 313)

Primary Endpoint:

  • Intubation or death at Day 30

Key Secondary Endpoints:

  • Time to intubation or death by Day 30
  • Mortality at Day 30 and Day 90
  • ICU LOS by Day 30
  • Need for renal dialysis by Day 30
  • SAE by Day 30

Participant Characteristics:

  • Mean age 68 years; 59% men
  • 84% receiving systemic corticosteroids at enrollment

Primary Outcome:

  • Intubation or death occurred in 32% of patients in CP arm and 28% in SOC arm (relative risk 1.16; 95% CI, 0.94–1.43, P = 0.18).

Secondary Outcomes:

  • By Day 30, no difference between the CP and SOC arms in:
    • Time to intubation or death
    • All-cause mortality (23% in CP arm vs. 21% in SOC arm)
    • ICU LOS (mean 4.3 days in CP arm vs. 3.7 days in SOC arm)
    • Need for renal dialysis (1.6% in CP arm vs. 2.0% in SOC arm)
  • More SAEs reported in CP arm (33% vs. 26% in SOC arm)
Key Limitations:
  • Open-label study
  • Trial stopped after 78% of planned enrollment after meeting prespecified futility criteria for early termination

Interpretation:

  • There was no benefit of CP in oxygen-dependent, hospitalized COVID-19 patients within 12 days of symptom onset.
RECOVERY Trial: Open-Label RCT of High-Titer Convalescent Plasma in Hospitalized Patients in the United Kingdom3
Key Inclusion Criteria:
  • Hospitalized patients with clinically suspected or laboratory-confirmed SARS-CoV-2 infection

Key Exclusion Criteria:

  • CP contraindicated

Interventions

  • 2 units high-titer CP (IgG SARS-CoV-2 spike protein ratio ≥6.0), first unit ASAP after randomization, second unit ≥12 hours later the next day (n = 5,795)
  • Usual care (n = 5,763)

Primary Endpoint:

  • All-cause mortality at Day 28

Key Secondary Endpoints:

  • Time to hospital discharge by Day 28
  • Among patients not receiving MV, receipt of MV or death by Day 28

Participant Characteristics:

  • Mean age 63.5 years; 64% men
  • 5% on MV
  • 92% received corticosteroids

Primary Outcomes:

  • No difference between the arms in:
    • Mortality (24% in each arm).
    • Mortality in patients without detectable SARS-CoV-2 antibodies (32% in CP arm and 34% in SOC arm).

Secondary Outcomes:

  • No difference between the arms in:
    • Proportion of patients discharged (66% in CP arm and 67% in SOC arm).
    • Proportion of patients who progressed to MV or death (28% in CP arm and 29% in SOC arm).
Key Limitations:
  • Open-label study

Interpretation:

  • There was no benefit of CP in hospitalized patients with COVID-19.
PLACID Trial: Open-Label RCT of Convalescent Plasma in Hospitalized Adults With Severe COVID-19 in India4
Key Inclusion Criteria:
  • Hospitalized patients with moderate, laboratory-confirmed SARS-CoV-2 infection
  • PaO2/FiO2 200–300 mm Hg or respiratory rate >24 breaths/min with SpO2 ≤93% on room air
Key Exclusion Criteria:
  • Critical illness

Interventions

  • 2 doses of 200 mL of CP transfused 24 hours apart (n = 235)
  • SOC (n = 229)

Primary Endpoint:

  • Progression to severe disease (defined as PaO2/FiO2 <100 mm Hg) or death within 28 days

Participant Characteristics:

  • Median age 52 years; 76% men
  • Higher prevalence of DM in CP arm (48%) than SOC arm (38%)

Primary Outcomes:

  • No difference in proportion of patients who progressed to severe disease or death between CP arm (19%) and SOC arm (18%) (risk ratio 1.04; 95% CI, 0.71–1.54).
  • Among patients without detectable SARS-CoV-2 neutralizing antibody titers at baseline (n = 70), no difference in proportion of patients who progressed to severe disease or death in CP arm and SOC arm (30% vs. 25%; risk ratio 1.2; 95% CI, 0.6–2.6).
Key Limitations:
  • Open-label study
  • SARS-CoV-2 antibody testing not used to select CP; many participants may have received low-titer CP

Interpretation:

  • CP use did not reduce progression to severe disease or death in hospitalized patients with moderate COVID-19.
PlasmAr Study: Double-Blind RCT of Convalescent Plasma in Hospitalized Adults in Argentina5
Key Inclusion Criteria:
  • PCR-confirmed, severe COVID-19
Key Exclusion Criteria:
  • Critical illness

Interventions:

  • 1 unit CP with SARS-CoV-2 viral spike-RBD IgG titer ≥1:800 (n = 228)
  • Placebo (n = 106)

Primary Endpoint:

  • Clinical status at 30 days (ordinal score)

Participant Characteristics:

  • Median age 62 years; 68% men
  • 65% with coexisting condition

Primary Outcome:

  • No significant difference between the arms in clinical status at 30 days (OR 0.83; 95% CI, 0.52–1.35; P = 0.46).
  • 30-day mortality 11% in both arms.
Key Limitations:
  • Small sample size

Interpretation:

  • There was no benefit of CP in hospitalized patients with severe COVID-19.
Multicenter, Double-Blind RCT of Convalescent Plasma in Hospitalized Adults With Severe COVID-19 in the United States and Brazil6
Key Inclusion Criteria:
  • Severe COVID-19 pneumonia
  • SpO2 ≤94% on room air or requirement of supplemental oxygen, MV, or ECMO
Key Exclusion Criteria:
  • >5 days on MV or ECMO
  • Severe multiorgan failure

Interventions:

  • Single dose of CP with SARS-CoV-2 spike-RBD IgG titer ≥1:400 (n = 150)
  • Non-SARS-CoV-2 plasma (control) (n = 73)

Primary Endpoint:

  • Clinical status on Day 28 (ordinal score)

Key Secondary Endpoints:

  • In-hospital and 28-day mortality
  • Time to clinical improvement
  • Time to discontinuation of supplemental oxygen
  • Time to hospital discharge

Participant Characteristics:

  • Median age 61 years; 66% men
  • 57% required supplemental oxygen at baseline: 25% high-flow oxygen or NIV and 13% MV or ECMO
  • 81% received corticosteroids

Primary Outcome:

  • No difference in Day 28 clinical status between the arms (OR 1.5; 95% CI, 0.83–2.68; P = 0.18).

Secondary Outcomes:

  • In-hospital mortality lower in CP arm than control arm (13% vs. 25%; OR 0.44; 95% CI, 0.22–0.91; P = 0.034). The difference was no longer significant after adjustment for age, sex, and duration of symptoms.
  • No difference between CP arm and control arm in median time to:
    • Clinical improvement (5 vs. 7 days).
    • Discontinuation of supplemental oxygen (6 vs. 7 days).
    • Hospital discharge (9 vs. 8 days).
Key Limitations:
  • Small sample size
  • Control arm intervention was blood plasma without SARS-CoV-2 antibodies, therefore not possible to identify potential harm due to plasma infusion

Interpretation:

  • Although the difference in clinical status on Day 28 between the arms was not statistically significant, lower 28-day mortality in the CP arm suggests potential benefit of CP in hospitalized patients with severe COVID-19
Double-Blind RCT of Early High-Titer Convalescent Plasma Therapy to Prevent Severe COVID-19 in Nonhospitalized Older Adults in Argentina7
Key Inclusion Criteria:
  • Nonhospitalized
  • Aged ≥75 years or aged 65–74 years with ≥1 coexisting condition
  • Mild COVID-19 with symptoms for <72 hours
Key Exclusion Criteria:
  • Severe respiratory disease

Interventions:

  • 250 mL of CP with IgG against SARS-CoV-2 spike protein >1:1,000 (n = 80)
  • Placebo (n = 80)

Primary Endpoint:

  • Severe respiratory disease, defined as respiratory rate ≥30 breaths/min and/or SpO2 <93% on room air by Day 15

Participant Characteristics:

  • Mean age 77 years; 38% men
  • Most with comorbidities

Primary Outcome:

  • 16% of patients in CP arm and 31% in placebo arm experienced severe respiratory disease by Day 15 (relative risk 0.52; 95% CI, 0.29–0.94; P = 0.03).
Key Limitations:
  • Small sample size
  • Early termination because COVID-19 cases decreased

Interpretation:

  • This trial demonstrated a benefit of CP in older adult outpatients with <72 hours of mild COVID-19 symptoms.
C3PO: Multicenter, Single-Blind RCT of High-Titer Convalescent Plasma in the United States8
Key Inclusion Criteria:
  • ED patient with ≤7 days of symptoms
  • PCR-confirmed SARS-CoV-2 infection
  • Aged ≥50 years or aged ≥18 years with ≥1 risk factor for disease progression
Key Exclusion Criteria:
  • Need for supplemental oxygen

Interventions:

  • 250 mL high-titer CP (median titer 1:641) (n = 257)
  • Placebo (n = 254)

Primary Endpoint:

  • Disease progression, defined as hospital admission, death, or seeking emergency or urgent care within 15 days of randomization

Key Secondary Endpoints:

  • Severity of illness (ordinal score)
  • All-cause mortality within 30 days
  • Hospital-free days over 30 days

Participant Characteristics:

  • Median age 54 years; 46% men
  • More patients with immunosuppression in CP arm (33 [13%]) than in placebo arm (17 [7%])
  • More patients with ≥3 risk factors in CP arm (141 [55%]) than in placebo arm (123 [48%])

Primary Outcomes:

  • There was no difference between the arms in the number of patients with disease progression: 77 (30%) in CP arm vs. 81 (32%) in placebo arm (risk difference 1.9%; 95% CrI, -6.0% to 9.8%).
  • 25 patients (19 in CP arm and 6 in placebo arm) required hospitalization during the index visit. In a post hoc analysis that excluded these patients, disease progression occurred in 24% of patients in CP arm vs. 30% in placebo arm (risk difference 5.8% [-1.9% to 13.6%]).

Secondary Outcomes:

  • 5 patients (1.9%) in CP arm and 1 patient (0.4%) in placebo arm died.
  • No difference in scores for illness severity or mean number of hospital-free days between the CP and placebo arms.
Key Limitations:
  • Imbalance of patients requiring hospital admission during the index visit included in the primary analysis
  • Slightly more patients with multiple risk factors, including immunosuppression, in CP arm

Interpretation:

  • In outpatients with COVID-19 at high risk of severe disease, use of high-titer CP within 1 week of symptom onset did not prevent disease progression.
Retrospective Evaluation of Convalescent Plasma Antibody Levels and the Risk of Death From COVID-19 in the United States9
Key Inclusion Criteria:
  • Severe or life-threatening COVID-19
  • Patients for whom samples of transfused CP were available for retrospective analysis of antibody titer

Intervention:

  • High-titer CP (n = 515), medium-titer CP (n = 2,006), or low-titer CP (n = 561), characterized retrospectively

Primary Endpoint:

  • Mortality at 30 days after CP transfusion

Participant Characteristics:

  • 31% aged ≥70 years; 61% men; 48% White, 37% Hispanic/Latinx
  • 61% in ICU; 33% on MV
  • 51% received corticosteroids and 31% received RDV

Primary Outcomes:

  • Mortality at 30 days after transfusion was 22% in high-titer CP arm, 27% in medium-titer CP arm, and 30% in low-titer CP arm.
    • Patients in high-titer CP arm had a lower risk of death than those in low-titer CP arm (relative risk 0.75; 95% CI, 0.61–0.93).
  • Mortality was lower among patients who were not receiving MV before CP transfusion (relative risk 0.66; 95% CI, 0.48–0.91).
  • Among the patients who were on MV before the CP transfusion, there was no difference in mortality between the high-titer and low-titer arms (relative risk 1.02; 95% CI, 0.78–1.32).
Key Limitation:
  • Lack of untreated control arm

Interpretation:

  • The study data are not sufficient to establish the efficacy or safety of COVID-19 CP.

References

  1. Writing Committee for the REMAP-CAP Investigators, Estcourt LJ, Turgeon AF, et al. Effect of convalescent plasma on organ support-free days in critically ill patients with COVID-19: a randomized clinical trial. JAMA. 2021;326(17):1690-1702. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34606578.
  2. Begin P, Callum J, Jamula E, et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med. 2021;27(11):2012-2024. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34504336.
  3. RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet. 2021;397(10289):2049-2059. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34000257.
  4. Agarwal A, Mukherjee A, Kumar G, et al. Convalescent plasma in the management of moderate COVID-19 in adults in India: open label Phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020;371:m3939. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33093056.
  5. Simonovich VA, Burgos Pratx LD, Scibona P, et al. A randomized trial of convalescent plasma in COVID-19 severe pneumonia. N Engl J Med. 2021;384(7):619-629. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33232588.
  6. O'Donnell MR, Grinsztejn B, Cummings MJ, et al. A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19. J Clin Invest. 2021;131(13). Available at: https://www.ncbi.nlm.nih.gov/pubmed/33974559.
  7. Libster R, Perez Marc G, Wappner D, et al. Early high-titer plasma therapy to prevent severe COVID-19 in older adults. N Engl J Med. 2021;384(7):610-618. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33406353.
  8. Korley FK, Durkalski-Mauldin V, Yeatts SD, et al. Early convalescent plasma for high-risk outpatients with COVID-19. N Engl J Med. 2021;385(21):1951-1960. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34407339.
  9. Joyner MJ, Carter RE, Senefeld JW, et al. Convalescent plasma antibody levels and the risk of death from COVID-19. N Engl J Med. 2021;384(11):1015-1027. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33523609.