CPT Pharmacometrics Syst Pharmacol. 2022 Mar 14. doi: 10.1002/psp4.12784. Online ahead of print.
ABSTRACT
The relationship between SARS-CoV-2 viral load reduction and disease symptom resolution remains largely undefined for COVID-19. While vaccine-derived immunity takes time to develop, neutralizing monoclonal antibodies offer immediate, passive immunity to patients with COVID-19. Bamlanivimab and etesevimab are two potent neutralizing monoclonal antibodies directed to the receptor binding domain (RBD) of the spike (S) protein of SARS-CoV-2. This study aims to describe the relationship between viral load and resolution of 8 common COVID-19-related symptoms in patients following treatment with neutralizing monoclonal antibodies (bamlanivimab alone or bamlanivimab and etesevimab together), in a Phase 2 clinical trial. Corresponding pharmacokinetics (PK), viral load and COVID-19-related symptom data were modelled using Nonlinear Mixed Effects Modeling (NONMEM) to describe the time-course of 8 COVID-19-related symptoms in an ordered categorical manner (none, mild, moderate, severe), following administration of bamlanivimab or bamlanivimab and etesevimab together to participants with COVID-19. The PK/PD models characterized the exposure-viral load-symptom time course of the 8 pre-selected COVID-19-related symptoms. Baseline viral load (BVL), change in viral load from baseline (ΔVL) and time since the onset of symptoms, demonstrated statistically significant effects on symptom score probabilities. Higher BVL generally indicated an increased probability of symptom severity. The severity of symptoms decreased over time, partially driven by the decrease in viral load. The effect of increasing time resulting in decreased severity of symptoms was over and above the effect of decreasing viral load. Administration of bamlanivimab alone or together with etesevimab results in a faster time to resolution of COVID-19-related symptoms compared to placebo.
PMID:35289125 | DOI:10.1002/psp4.12784
