Estimation of viral kinetics model parameters in young and aged SARS-CoV-2 infected macaques

Abstract

The SARS-CoV-2 virus disproportionately causes serious illness and death in older individuals. In order to have the greatest impact in decreasing the human toll caused by the virus, antiviral treatment should be targeted to older patients. For this, we need a better understanding of the differences in viral dynamics between SARS-CoV-2 infection in younger and older adults. In this study, we use previously published averaged viral titre measurements from the nose and throat of SARS-CoV-2 infection in young and aged cynomolgus macaques to parametrize a viral kinetics model. We find that all viral kinetics parameters differ between young and aged macaques in the nasal passages, but that there are fewer differences in parameter estimates from the throat. We further use our parametrized model to study the antiviral treatment of young and aged animals, finding that early antiviral treatment is more likely to lead to a lengthening of the infection in aged animals, but not in young animals.

Modeling explains prolonged SARS-CoV-2 nasal shedding relative to lung shedding in remdesivir-treated rhesus macaques

“…Here, we apply mathematical models to remdesivir treatment data in rhesus macaques in which both lung and nasal viral load were measured. We believe that our model explains the observed data in its entirety and allows several testable hypotheses not generated by existing models (Gonc ¸alves et al, 2021;Kim et al, 2021b;Rodriguez and Dobrovolny, 2021). Specifically, our model provides a plausible explanation for prolonged viral shedding in nasal passages in treated animals while also capturing lower lung viral load kinetics and limited pulmonary pathology in treated animals.…”

“…Several mathematical models have been developed detailing SARS-CoV-2 viral kinetics in humans (Cao et al, 2021;Goyal et al, 2020;Ke et al, 2021aKe et al, , 2021bKim et al, 2021a;Ne ´ant et al, 2021), nonhuman primates (Dobrovolny, 2020;Gonc ¸alves et al, 2021;Kim et al, 2021b;Rodriguez and Dobrovolny, 2021), and ferrets (Vaidya et al, 2021). The general structure follows a target cell-limited model with or without innate and adaptive immune responses.…”

Predicting the Cross-Coordinated Immune Response Dynamics in Sars-Cov-2 Infection: Implications for Disease Pathogenesis

“…the broadness of engaged organs and physiological systems to be considered in the models, and the lack of coherent time-series data on the immune response to infection which are required to robustly calibrate the described processes. So far, more than a dozen of mathematical models of SARS-CoV-2 infection have been developed [3][4][5][6][7][8][9][10][11][12][13][14][16][17][18][19][20][21]. They differ enormously in their complexity, ranging from low-dimensional models (e.g., the ODE systems of two to five equations) [4,5,7,11,16]) through medium-size models (about ten equations) [3,6,8,13,14,17,21] up to high resolution models of ODEs (up to 60 equations) [9,10] or hybrid multi-scale models [18,20].…”

“…So far, more than a dozen of mathematical models of SARS-CoV-2 infection have been developed [3][4][5][6][7][8][9][10][11][12][13][14][16][17][18][19][20][21]. They differ enormously in their complexity, ranging from low-dimensional models (e.g., the ODE systems of two to five equations) [4,5,7,11,16]) through medium-size models (about ten equations) [3,6,8,13,14,17,21] up to high resolution models of ODEs (up to 60 equations) [9,10] or hybrid multi-scale models [18,20]. The later can be categorized as "experimental mathematical" models.…”

“…predicting the effect of therapies [4,[7][8][9][10]12]; • relationship between the disease phenotype and immune response parameters [4,7,11,13,19]; • effect of aging on disease course [7,14].…”