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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.
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.
  • Harvala H; National Microbiology Services, NHS Blood and Transplant, London, UK.
  • Robb ML; Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, UK.
  • Watkins N; Department of Research and Development, NHS Blood and Transplant Cambridge, Cambridge, UK.
  • Ijaz S; Virology Reference Department, National Infection Service, Public Health England, London, UK.
  • Dicks S; Virology Reference Department, National Infection Service, Public Health England, London, UK.
  • Patel M; High Containment Microbiology, National Infection Service, Public Health England, London, UK.
  • Supasa P; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Wanwisa D; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Liu C; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Mongkolsapaya J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Bown A; Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • Bailey D; Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, Wiltshire, UK.
  • Vipond R; Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, Wiltshire, UK.
  • Grayson N; Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, Wiltshire, UK.
  • Temperton N; Department of Paediatric Medicine, University of Oxford, University of Oxford, Oxford, UK.
  • Gupta S; Medway School of Pharmacy, University of Kent, Chatham, UK.
  • Ploeg RJ; Department of Zoology, University of Oxford, Oxford, UK.
  • Bolton J; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • Fyfe A; Department of Transplant Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Gopal R; Department of Zoology, University of Oxford, Oxford, UK.
  • Simmonds P; Department of Zoology, University of Oxford, Oxford, UK.
  • Screaton G; Virology Reference Department, National Infection Service, Public Health England, London, UK.
  • Thompson C; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Brooks T; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Zambon M; Department of Zoology, University of Oxford, Oxford, UK.
  • Miflin G; Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, Wiltshire, UK.
  • Roberts DJ; Virology Reference Department, National Infection Service, Public Health England, London, UK.
Transfus Med ; 31(3): 167-175, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-979626
ABSTRACT

INTRODUCTION:

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 120 were detected in 43 samples (83% of those tested) and >1100 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 >1100 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Humans / Male Language: English Journal: Transfus Med Journal subject: Hematology Year: 2021 Document Type: Article Affiliation country: Tme.12746

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Humans / Male Language: English Journal: Transfus Med Journal subject: Hematology Year: 2021 Document Type: Article Affiliation country: Tme.12746