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JCI Insight
. 2021 Dec 2;e151518.
doi: 10.1172/jci.insight.151518. Online ahead of print.
Pharmacokinetics of high-titer anti-SARS-CoV-2 human convalescent plasma in high-risk children
Oren Gordon 1 , Mary Katherine Brosnan 1 , Steve Yoon 2 , Dawoon Jung 3 , Kirsten Littlefield 2 , Abhinaya Ganesan 2 , Christopher A Caputo 2 , Maggie Li 2 , William R Morgenlander 4 , Stephanie N Henson 4 , Alvaro A Ordonez 4 , Patricia De Jesus 4 , Elizabeth W Tucker 5 , Nadine Peart Akindele 4 , Zexu Ma 2 , Jo Wilson 2 , Camilo A Ruiz-Bedoya 4 , M Elizabeth M Younger 1 , Evan M Bloch 6 , Shmuel Shoham 5 , David Sullivan 2 , Aaron Ar Tobian 4 , Kenneth R Cooke 7 , Ben Larman 4 , Jogarao Vs Gobburu 3 , Arturo Casadevall 2 , Andrew Pekosz 2 , Howard M Lederman 1 , Sabra L Klein 2 , Sanjay K Jain 1
Affiliations
- PMID: 34855624
- DOI: 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.
Keywords: COVID-19; Immunoglobulins; Infectious disease.