Pharmacokinetics of high-titer anti-SARS-CoV-2 human convalescent plasma in high-risk children
Author
Gordon, OrenBrosnan, 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
Date
2021-12-02Journal
JCI InsightPublisher
American Society for Clinical InvestigationType
Article
Metadata
Show full item recordAbstract
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.Identifier to cite or link to this item
http://hdl.handle.net/10713/17319ae974a485f413a2113503eed53cd6c53
10.1172/jci.insight.151518