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Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels
Author(s) -
Harvala Heli,
Robb Matthew L.,
Watkins Nick,
Ijaz Samreen,
Dicks Steven,
Patel Monika,
Supasa Piyada,
Wanwisa Dejnirattisai,
Liu Chang,
Mongkolsapaya Juthathip,
Bown Abbie,
Bailey Daniel,
Vipond Richard,
Grayson Nicholas,
Temperton Nigel,
Gupta Sunetra,
Ploeg Rutger J.,
Bolton Jai,
Fyfe Alex,
Gopal Robin,
Simmonds Peter,
Screaton Gavin,
Thompson Craig,
Brooks Tim,
Zambon Maria,
Miflin Gail,
Roberts David J.
Publication year - 2021
Publication title -
transfusion medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.471
H-Index - 59
eISSN - 1365-3148
pISSN - 0958-7578
DOI - 10.1111/tme.12746
Subject(s) - antibody , medicine , immunology , covid-19 , coronavirus , immunoassay , virology , immunoglobulin g , immune system , disease , infectious disease (medical specialty)
The lack of approved specific therapeutic agents to treat coronavirus disease (COVID‐19) associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS‐CoV‐2 proteins in scalable assays will be crucial for the success of a large‐scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme‐linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. Methods Blood samples were collected from 52 individuals with a previous laboratory‐confirmed SARS‐CoV‐2 infection. These were assayed for SARS‐CoV‐2 nAbs by microneutralisation and pseudo‐type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. Results All samples contained SARS‐CoV‐2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). Discussion Robust associations between nAb titres and reactivity in several ELISA‐based antibody tests demonstrate their possible utility for scaled‐up production of convalescent plasma containing potentially therapeutic levels of anti‐SARS‐CoV‐2 nAbs.