Barcoded SARS-CoV-2 viruses define the impact of duration and route of exposure on the transmission bottleneck in a hamster model.

Summary

Using >200 isogenic barcoded SARS-CoV-2 variants in hamsters, longer and more direct exposures increased the transmission bottleneck, and barcode enumeration across upper and lower airways showed the upper airway as the primary source of transmitted virus. The barcoded-virus platform provides a rigorous tool to quantify transmission dynamics.

Key Findings

• Generated a pool of >200 isogenic, 6-nt barcoded SARS-CoV-2 variants via reverse genetics.
• Longer and more direct exposure increased the transmission bottleneck size.
• Barcode profiling across nasal turbinates, trachea, and lungs identified the upper airway as the primary source of transmitted virus.

Clinical Implications

While preclinical, findings support targeting upper airway viral load and minimizing prolonged/direct exposure in infection control. Barcoding approaches can inform variant fitness and transmission risk assessments.

Limitations

• Hamster model may not fully recapitulate human transmission dynamics
• Barcoding, while designed isogenic, could still subtly affect fitness or detection biases

Future Directions

Translate to human challenge or household transmission studies; integrate with immune status and variant-specific fitness; apply to other respiratory viruses to generalize bottleneck principles.