Exposure route drives SARS-CoV-2 infection patterns in non-human primates

Area of Science:

• Infectious Diseases
• Virology
• Animal Models

Background:

• Understanding infectious disease progression is vital for public health policy and clinical interventions.
• Animal infection experiments are crucial for studying complex, multi-scale disease processes.
• Previous studies show dose and route of exposure influence within-host dynamics, but quantification is limited by small sample sizes.

Purpose of the Study:

• To quantify how exposure conditions and demographic factors shape within-host SARS-CoV-2 infection kinetics.
• To analyze the largest published database of non-human primate challenge experiments.
• To determine the relative impact of exposure route versus dose on infection dynamics.

Main Methods:

• Compiled and analyzed a large database of 107 non-human primate challenge experiments (721 animals, 22,183 observations).
• Focused on SARS-CoV-2 infection kinetics in the respiratory and gastrointestinal tracts.
• Utilized meta-analysis to overcome limitations of individual studies.

Main Results:

• Exposure route had a stronger effect on infection kinetics than dose, age, sex, or species.
• Directly exposed tissues showed distinct spatiotemporal kinetics compared to non-exposed tissues.
• Estimated 50% infectious doses varied greatly by exposure route, and dose effects were route- and tissue-specific.

Conclusions:

• Exposure route is a primary driver of SARS-CoV-2 infection kinetics in non-human primates.
• Meta-analysis of animal experiments can yield significant insights into disease dynamics.
• Findings support the use of exposure route as a critical factor in translational medicine and infectious disease modeling.