1. Viral dynamics model

Temporal change in viral load (i.e., viral dynamics) of viruses causing acute respiratory infection including SARS-CoV-2 has been described by a simple mathematical model, commonly referred to as the target cell limited model (Panel A) with only three variables T(t), I(t), and V(t), which  are the numbers of uninfected target cells, infected target cells, and the amount of virus at time , respectively. The model accounts for the fundamental biological process of the infection within a host, such as viral replication and elimination due to immune response and explains the longitudinal viral load data (Panel B). However, the mechanism is not that simple and different between viruses.

We aim to build on top of this simple model by including compelling new features as driven by new empirical evidence on SARS-CoV-2 viral dynamics. For example, recent literature suggests that the difference in response of adaptive immunity, such as cytotoxic T lymphocytes and antibody, may contribute to determine the mortality risk. Therefore, we plan to extend the model to explicitly include adaptive immunity reaction to SARS-CoV-2 infection (Panel A). Further, the model will be extended to incorporate the effect of the treatment. We will primarily consider three mechanisms of action: (①) blocking virus production; (②) blocking de novo infection; and (③) promoting cytotoxicity (Panel A).