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Neutralizing activity to SARS‐CoV ‐2 of convalescent and control plasma used in a randomized controlled trial
Author(s) -
Freedenberg Alex T.,
Pan ChunHao,
Diehl William E.,
Romeiser Jamie L.,
Hwang GaRam,
Leiton Cindy V.,
Muecksch Frauke,
Shroyer Kenneth R.,
BennettGuerrero Elliott
Publication year - 2021
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.16283
Subject(s) - convalescent plasma , covid-19 , randomized controlled trial , sars virus , medicine , virology , betacoronavirus , immunology , outbreak , disease , infectious disease (medical specialty)
Background There are limited data on the neutralizing activity of convalescent plasma (CP) administered in randomized controlled trials (RCT) of COVID‐19 infection. Study Design and Methods As part of an RCT, CP was collected per FDA guidelines from individuals recovered from COVID‐19 infection. CP donors had to have ≥145 optical density (OD) units (ideal target ≥300) using a semiquantitative, immunochromatographic test for IgG antibody to the nucleocapsid protein (NP) of SARS‐CoV‐2 (typical range 0–500 OD units). A random subset of samples [14 control plasma, 12 CP “medium‐anti‐NP” (145–299 OD units), and 13 CP “high” anti‐NP (≥300 OD units)] were tested for neutralizing antibodies using an established viral luciferase antibody inhibition assay to detect the infection of SARS‐CoV‐2 pseudovirus that encoded spike protein (SARS2‐S trunc ) on a human immunodeficiency virus 1 vector (NL43dEnvNanoLuc), using ACE2‐expressing 293 T cells. The titer needed to neutralize 50% of viral activity (NT50) was calculated. Results The uptake of SARS‐CoV‐2 pseudovirus by 293T ACE2 cells was inhibited by pretreatment with CP compared to control CP ( p < .001) with control plasma having a median (IQR) 50% neutralization titer (NT50) of 1:28 (1:16,1:36) compared to 1:334 (1:130,1:1295) and 1:324 (1:244,1:578), for medium anti‐NP and high anti‐NP CP units, respectively. The neutralizing activity of CP met minimum FDA criteria with neutralizing antibody titers >1:80 in 100% of randomly selected samples, using a conservative approach that excluded non‐specific binding. Discussion Plasma from donors screened using an immunochromatographic test for IgG antibody to SARS‐CoV‐2 NP exhibited neutralizing activity meeting FDA's minimum standard in all randomly selected COVID‐19 CP units.