What is the role of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19)?

Updated: Oct 20, 2020
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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The FDA granted emergency use authorization (EUA) on August 23, 2020 for use of convalescent plasma in hospitalized patients with COVID-19. Convalescent plasma contains antibody-rich plasma products collected from eligible donors who have recovered from COVID-19. An expanded access program (EAP) for convalescent plasma was initiated in early April 2020. [26, 297]  The Mayo Clinic coordinated the open-access COVID-19 expanded access program, but will discontinue enrollment on August 28, as the FDA authorizes emergency use.For further information regarding administration, see the EUA COVID-19 Convalescent Fact Sheet for Health Care Providers.

Additionally, the CoVIg-19 Plasma Alliance is a partnership of numerous pharmaceutical companies who are collecting, developing, producing, and distributing immunoglobulin from patients with confirmed COVID-19 infection who have recovered.

Preliminary data from an open-label, multicenter, expanded access program in hospitalized adults conducted by the Mayo Clinic observed a gradient mortality in relation to IgG antibody levels in transfused ABO-compatible human COVID-19 convalescent plasma. The study analysis is from 2,807 acute care facilities in the US and territories and 5000 participants. The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the ICU and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The 7-day mortality rate in patients who received a high-antibody product was 8.7% in patients transfused within 3 days of COVID-19 diagnosis compared with 11.9% patients transfused 4 or more days after diagnosis (p < 0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p < 0.0001). [299] Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma – the pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared with to low antibody level plasma units. The incidence of serious adverse events, including mortality rate (0.3%) within the first 4 hours after transfusion was < 1%. [295]  

The NIH COVID-19 Guidelines Panel further evaluated the Mayo Clinic’s EAP data and further reviewed subgroups. Among patients who were not intubated, 11% of those who received convalescent plasma with high antibody titers died within 7 days of transfusion compared with 14% of those who received convalescent plasma with low antibody titers. Among those who were intubated, there was no difference in 7-day survival. Based on the available evidence, as of August 27, 2020, the Panel concluded there are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19. [300]

Similar observations were published from a study at Houston Methodist Hospital.  Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 nontransfused control patients with COVID-19. Matching criteria included age, sex, BMI, comorbidities, and baseline ventilation requirement 48 hours from admission, and in a second matching analysis, ventilation status at Day 0. Variability in the timing of transfusion relative to admission and titer of antibodies of plasma transfused allowed for analysis in specific matched cohorts. The analysis showed a significant reduction (P = 0.047) in mortality within 28 days in patients transfused within 72 hours of admission with plasma that measured an anti-spike protein receptor binding domain titer of 1:1350 or greater. [306]

The use of convalescent plasma has a long history in the treatment of infectious diseases. Writing in the Journal of Clinical Investigation Casadevall and Pirofski [303]  proposed using it as a treatment for COVID-19, and Bloch et al  [304]  laid out a conceptual framework for implementation. Two small case series reported improvement in oxygenation, sequential organ failure assessment (SOFA) scores, and eventual ventilator weaning in some patients. The timelines of improvement varied from days to weeks. Caution is advised, as these were not controlled trials and other pharmacologic methods (antivirals) were used in some patients. [305, 298]  

A Cochrane review of convalescent plasma use in patients with COVID-19 is perpetually being updated as data emerge. As of July 10, 2020, the review included 20 studies with 5443 participants, of whom 5211 received convalescent plasma. Among these studies was one randomized controlled trial with 103 participants (52 received convalescent plasma). At the time of publication, the authors expressed uncertainty as to the benefits of convalescent plasma in terms of affecting mortality at hospital discharge, prolonging time to death, or improving clinical symptoms at 7 or 28 days. [307]

A meta-analysis of 15 controlled studies showed a significantly lower mortality rate in patients with COVID-19 who received convalescent plasma compared with control groups. However, the authors point out that the studies were mostly of low or very low quality with a moderate or high risk of bias. [308]

An open-label study (n = 103) of patients with laboratory-confirmed COVID-19 in Wuhan, China, given convalescent plasma did not result in a statistically significant improvement in time to clinical improvement within 28 days compared with standard of care alone. [309]

A nonrandomized study transfused patients based on supplemental oxygen needs with convalescent plasma from donors with a SARS-CoV-2 anti-spike antibody titer of at least 1:320 dilution. Matched control patients were retrospectively identified within the electronic health record database. Supplemental oxygen requirements and survival were compared between plasma recipients and controls. Results showed convalescent plasma transfusion improved survival in nonintubated patients (P = 0.015), but not in intubated patients (P = 0.752). [310]

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