Modeling Within-Host Dynamics of SARS-CoV-2 Infection: A Case Study in Ferrets.

Naveen K. Vaidya,Alan S. Perelson,Angelica Bloomquist

doi:10.3390/v13081635

Naveen K. Vaidya, Alan S. Perelson + Show 1 more

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https://doi.org/10.3390/v13081635

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Abstract

The pre-clinical development of antiviral agents involves experimental trials in animals and ferrets as an animal model for the study of SARS-CoV-2. Here, we used mathematical models and experimental data to characterize the within-host infection dynamics of SARS-CoV-2 in ferrets. We also performed a global sensitivity analysis of model parameters impacting the characteristics of the viral infection. We provide estimates of the viral dynamic parameters in ferrets, such as the infection rate, the virus production rate, the infectious virus proportion, the infected cell death rate, the virus clearance rate, as well as other related characteristics, including the basic reproduction number, pre-peak infectious viral growth rate, post-peak infectious viral decay rate, pre-peak infectious viral doubling time, post-peak infectious virus half-life, and the target cell loss in the respiratory tract. These parameters and indices are not significantly different between animals infected with viral strains isolated from the environment and isolated from human hosts, indicating a potential for transmission from fomites. While the infection period in ferrets is relatively short, the similarity observed between our results and previous results in humans supports that ferrets can be an appropriate animal model for SARS-CoV-2 dynamics-related studies, and our estimates provide helpful information for such studies.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes the infectious disease COVID-19 [1,2,3,4]
Our results provide evidence-based quantitative insights into within-host viral dynamics in animal models that can significantly benefit the control of SARS-CoV-2 infection in humans
For each best-fit parameter, we provide 95% confidence intervals (CI), which were computed from 250 replicates, by bootstrapping the residuals [53,54]

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes the infectious disease COVID-19 [1,2,3,4]. The ongoing global pandemic of COVID-19 has spread to almost all countries globally, with more than 178 million confirmed cases and more than 3.8 million deaths as of 21 June 2021 [5]. While tremendous efforts have been put into the control of COVID-19 outbreaks, these have mainly been nonpharmaceutical. The disease is still spreading because of vaccine hesitancy, the lack of availability of vaccines in most parts of the world, and the difficulties of getting vaccines into arms when it is available. The emergence of SARS-CoV-2 variants amplifies already existing substantial threats to global public health [6,7]

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