tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Mary Katherine Brosnan[SUP] 1 [/SUP], Steve Yoon[SUP] 2 [/SUP], Dawoon Jung[SUP] 3 [/SUP], Kirsten Littlefield[SUP] 2 [/SUP], Abhinaya Ganesan[SUP] 2 [/SUP], Christopher A Caputo[SUP] 2 [/SUP], Maggie Li[SUP] 2 [/SUP], William R Morgenlander[SUP] 4 [/SUP], Stephanie N Henson[SUP] 4 [/SUP], Alvaro A Ordonez[SUP] 4 [/SUP], Patricia De Jesus[SUP] 4 [/SUP], Elizabeth W Tucker[SUP] 5 [/SUP], Nadine Peart Akindele[SUP] 4 [/SUP], Zexu Ma[SUP] 2 [/SUP], Jo Wilson[SUP] 2 [/SUP], Camilo A Ruiz-Bedoya[SUP] 4 [/SUP], M Elizabeth M Younger[SUP] 1 [/SUP], Evan M Bloch[SUP] 6 [/SUP], Shmuel Shoham[SUP] 5 [/SUP], David Sullivan[SUP] 2 [/SUP], Aaron Ar Tobian[SUP] 4 [/SUP], Kenneth R Cooke[SUP] 7 [/SUP], Ben Larman[SUP] 4 [/SUP], Jogarao Vs Gobburu[SUP] 3 [/SUP], Arturo Casadevall[SUP] 2 [/SUP], Andrew Pekosz[SUP] 2 [/SUP], Howard M Lederman[SUP] 1 [/SUP], Sabra L Klein[SUP] 2 [/SUP], Sanjay K Jain[SUP] 1 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Mary Katherine Brosnan[SUP] 1 [/SUP], Steve Yoon[SUP] 2 [/SUP], Dawoon Jung[SUP] 3 [/SUP], Kirsten Littlefield[SUP] 2 [/SUP], Abhinaya Ganesan[SUP] 2 [/SUP], Christopher A Caputo[SUP] 2 [/SUP], Maggie Li[SUP] 2 [/SUP], William R Morgenlander[SUP] 4 [/SUP], Stephanie N Henson[SUP] 4 [/SUP], Alvaro A Ordonez[SUP] 4 [/SUP], Patricia De Jesus[SUP] 4 [/SUP], Elizabeth W Tucker[SUP] 5 [/SUP], Nadine Peart Akindele[SUP] 4 [/SUP], Zexu Ma[SUP] 2 [/SUP], Jo Wilson[SUP] 2 [/SUP], Camilo A Ruiz-Bedoya[SUP] 4 [/SUP], M Elizabeth M Younger[SUP] 1 [/SUP], Evan M Bloch[SUP] 6 [/SUP], Shmuel Shoham[SUP] 5 [/SUP], David Sullivan[SUP] 2 [/SUP], Aaron Ar Tobian[SUP] 4 [/SUP], Kenneth R Cooke[SUP] 7 [/SUP], Ben Larman[SUP] 4 [/SUP], Jogarao Vs Gobburu[SUP] 3 [/SUP], Arturo Casadevall[SUP] 2 [/SUP], Andrew Pekosz[SUP] 2 [/SUP], Howard M Lederman[SUP] 1 [/SUP], Sabra L Klein[SUP] 2 [/SUP], Sanjay K Jain[SUP] 1 [/SUP]
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.