Neutralizing activity to SARS‐CoV‐2 of convalescent and control plasma used in a randomized controlled trial

• Published in: Transfusion 2021-05, Vol.61 (5), p.1363-1369
• Main Authors: Freedenberg, Alex T., Pan, Chun‐Hao, Diehl, William E., Romeiser, Jamie L., Hwang, Ga‐Ram, Leiton, Cindy V., Muecksch, Frauke, Shroyer, Kenneth R., Bennett‐Guerrero, Elliott
• Format: Article
• Language: English
• Subjects: ACE2; Adult; Angiotensin-converting enzyme 2; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Blood Donors; Brief Report; Brief Reports; Convalescence; COVID-19; COVID-19 - blood; Double-Blind Method; Female; FFP transfusion; HIV; Human immunodeficiency virus; Humans; IgG antibody; Immunoglobulin G; immunology (other than RBC serology); Infections; Lymphocytes; Lymphocytes T; Male; Middle Aged; Neutralization; Neutralizing; Nucleocapsids; Optical density; Plasma; Proteins; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike protein; Viral diseases
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.16283

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‐Strunc) 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 293TACE2 cells was inhibited by pretreatment with CP compared to control CP (p 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.