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    Pharmacokinetics of high-titer anti-SARS-CoV-2 human convalescent plasma in high-risk children

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    Author
    Gordon, Oren
    Brosnan, Mary Katherine
    Yoon, Steve
    Jung, Dawoon
    Littlefield, Kirsten
    Ganesan, Abhinaya
    Caputo, Christopher A
    Li, Maggie
    Morgenlander, William R
    Henson, Stephanie N
    Ordonez, Alvaro A
    De Jesus, Patricia
    Tucker, Elizabeth W
    Peart Akindele, Nadine
    Ma, Zexu
    Wilson, Jo
    Ruiz-Bedoya, Camilo A
    Younger, M Elizabeth M
    Bloch, Evan M
    Shoham, Shmuel
    Sullivan, David
    Tobian, Aaron Ar
    Cooke, Kenneth R
    Larman, Ben
    Gobburu, Jogarao Vs
    Casadevall, Arturo
    Pekosz, Andrew
    Lederman, Howard M
    Klein, Sabra L
    Jain, Sanjay K
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    Date
    2021-12-02
    Journal
    JCI Insight
    Publisher
    American Society for Clinical Investigation
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1172/jci.insight.151518
    Abstract
    Background: While most children experience mild COVID-19, high-risk children with underlying conditions may develop severe disease, requiring interventions. Kinetics of antibodies transferred via COVID-19 convalescent plasma early in disease, have not been characterized. Methods: In this study (NCT04377672), high-risk children were prospectively enrolled to receive high-titer COVID-19 convalescent plasma (>1:320 anti-spike IgG; Euroimmun). Passive transfer of antibodies and endogenous antibody production were serially evaluated for up to 2 months after transfusion. Commercial and research ELISA assays, virus neutralization assays, high-throughput phage-display assay utilizing a coronavirus epitope library and pharmacokinetic analyses were performed. Results: Fourteen high-risk children (median age 7.5 years) received high-titer COVID-19 convalescent plasma, nine children within five days (range 2-7) of symptom onset and five children within 4 days (range 3-5) after exposure to SARS-CoV-2. There were no serious adverse events related to transfusion. Antibodies to SARS-CoV-2 were transferred from the donor to the recipient, but antibody titers declined by 14-21 days with a 15.1-day t½ for spike protein IgG. Donor plasma had significant neutralization capacity which was transferred to the recipient. However, as early as 30 minutes post-transfusion, recipient plasma had low neutralization capacity. Conclusions: Convalescent plasma transfused to high-risk children appears to be safe with expected antibody kinetics, regardless of weight or age. However, current use of convalescent plasma in high-risk children achieves low neutralizing capacity.
    Keyword
    COVID-19
    Immunoglobulins
    Infectious disease
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17319
    ae974a485f413a2113503eed53cd6c53
    10.1172/jci.insight.151518
    Scopus Count
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    UMB Coronavirus Publications
    UMB Open Access Articles

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