Pharmacokinetics and Efficacy of Human Hyperimmune Intravenous Immunoglobulin Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Adult Syrian Hamsters.
Clin Infect Dis
; 75(1): e459-e465, 2022 08 24.
Article
em En
| MEDLINE
| ID: mdl-34554235
ABSTRACT
BACKGROUND:
After the failure of antibody therapies in treating hospitalized patients with coronavirus disease 2019 (COVID-19), we investigated the impact of viral replication on the pharmacokinetics and efficacy of a hyperimmune severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (CoVIG) product in treating SARS-CoV-2 infection using an adult Syrian hamster model.METHODS:
The CoVIG was manufactured from plasma donors who had recovered from COVID-19. The dose used (400 mg/kg) was based on the dose given in clinical trials to hospitalized patients with COVID-19. Hamsters were given a single dose of CoVIG 2 days after challenge with the SARS-CoV-2 virus (isolate NY/PV08410/2020), followed by sampling of blood, nasal, tracheal, and lung tissues at different time points. The blood samples were assayed for anti-SARS-CoV-2 spike binding and used to calculate pharmacokinetic (PK) parameters. Nasal wash, tracheal, and lung tissue samples were assayed for viral replication by polymerase chain reaction (subgenomic messenger RNA).RESULTS:
CoVIG-treated hamsters showed a reduction in viral replication in the lower respiratory tract, but minimal reduction in the upper respiratory tract, after challenge with SARS-CoV-2. Challenge resulted in altered PK parameters proportionate to viral replication, resulting in decreased area under the curve, accelerated clearance, and shorter half-life of CoVIG.CONCLUSIONS:
These data indicate that in the presence of actively replicating SARS-CoV-2 virus, PK parameters are altered and should trigger an adjustment in CoVIG dosing.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tratamento Farmacológico da COVID-19
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article