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.
Keywords: SARS-CoV-2; hamsters; immune globulin; pharmacokinetics; viral replication.
【저자키워드】 SARS-CoV-2, hamsters, pharmacokinetics, viral replication, immune globulin, 【초록키워드】 COVID-19, coronavirus disease, Efficacy, coronavirus, clinical trial, therapy, antibody, SARS-CoV-2 virus, nasal, anti-SARS-CoV-2, immune, Immunoglobulin, viral replication, challenge, plasma, hamster, upper respiratory tract, parameters, Blood, single dose, Donor, binding, pharmacokinetic, dose, Lower respiratory tract, Messenger RNA, acute respiratory syndrome, different time points, blood sample, lung tissue, clearance, hyperimmune, polymerase chain, resulting, investigated, were given, hospitalized patient, tracheal, reduction in, accelerated, lung tissue sample, PK parameter, the SARS-CoV-2 virus, treating SARS-CoV-2 infection, used to calculate, with COVID-19, 【제목키워드】 Human, coronavirus 2, hamster, respiratory,