Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma

Abstract

Description: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP.

Methods: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations.

Recommendation 1 (outpatient): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence).

Recommendation 2 (inpatient): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2.

Recommendation 3 (inpatient): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence).

Recommendation 4 (inpatient): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence).

Recommendation 5 (prophylaxis): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence).

Good clinical practice statement: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Appendix Figure.. PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) flow diagram.

Modeled using Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [PMID: 33782057] doi:10.1136/bmj.n71.

Figure 1.. CCP transfusion for outpatients with COVID-19.

The top panel compares CCP to standard of care or placebo with the outcome of need for hospitalization with need of at least oxygen by mask or nasal prongs or death. The bottom panel compares CCP to standard plasma with the outcome of need for hospitalization with need of at least oxygen by mask or nasal prongs or death. For risk of bias assessment explanation and GRADE assessment, see the Supplement Methods. For WHO grading, see Supplement Table 8. COnV-ert = Convalescent Methylene Blue Treated (MBT) Plasma for Early Treatment in Non-hospitalised Mild or Moderate COVID-19 Patients: a Randomized Double Blind Study; GRADE = Grading of Recommendations Assessment, Development and Evaluation; M–H = Mantel–Haenszel; WHO = World Health Organization.

Figure 2.. CCP transfusion versus standard of care or placebo for hospitalized patients.

The primary outcome was all-cause mortality at day 28. For risk of bias assessment explanation and GRADE assessment, see the Supplement Methods. df = degrees of freedom; GRADE = Grading of Recommendations Assessment, Development and Evaluation; M–H = Mantel–Haenszel.

Figure 3.. CCP transfusion versus standard of care or placebo stratified by status of SARS-CoV-2 antibodies at baseline.

The primary outcome was need for invasive mechanical ventilation or death at 28 days in hospitalized patients. For risk of bias assessment explanation and GRADE assessment, see the Supplement Methods. CP = convalescent plasma; df = degrees of freedom; EU = European Union; FDA = U.S. Food and Drug Administration; GRADE = Grading of Recommendations Assessment, Development and Evaluation; ICEMAN = Instrument to assess the Credibility of Effect Modification Analyses; M–H = Mantel–Haenszel; nAb = neutralizing antibody titer.

Figure 4.. CCP transfusion versus standard of care or placebo stratified by immunosuppression status.

The primary outcome was all-cause mortality at 28 days in hospitalized patients. For risk of bias assessment explanation and GRADE assessment, see the Supplement Methods. df = degrees of freedom; GRADE = Grading of Recommendations Assessment, Development and Evaluation; ICEMAN = Instrument to assess the Credibility of Effect Modification Analyses; M–H = Mantel–Haenszel.

Figure 5.. CCP transfusion versus standard plasma as prophylaxis to prevent infection with SARS-CoV-2 within 30 days.

For risk of bias assessment explanation and GRADE assessment, see the Supplement Methods. df = degrees of freedom; GRADE = Grading of Recommendations Assessment, Development and Evaluation; M–H = Mantel–Haenszel.