Characterization of pathogen-inactivated COVID-19 convalescent plasma and responses in transfused patients

Transfusion. 2022 Oct;62(10):1997-2011. doi: 10.1111/trf.17083. Epub 2022 Sep 5.

Abstract

Background: Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics.

Study design and methods: In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients.

Results: Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients.

Discussion: PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

Keywords: COVID-19; COVID-19 convalescent plasma; SARS-CoV2; neutralizing antibodies; pathogen-reduction treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Serotherapy
  • COVID-19* / therapy
  • Case-Control Studies
  • Humans
  • Immunization, Passive
  • Middle Aged
  • SARS-CoV-2*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral