Airborne transmission of respiratory viruses in healthcare settings is often underestimated because conventional epidemiologic methods provide limited insight into aerosol dynamics and ventilation performance. Integrating aerosol simulations with viral genomic data may support the plausibility of airborne transmission pathways and help explain differences in outbreak magnitude over time. We investigated two nosocomial SARS-CoV-2 clusters between January and April 2021 in a French university hospital. Patients and healthcare workers were screened by RT-PCR, and whole-genome sequencing was performed for samples with Ct <30. Computational fluid dynamics (CFD) simulations reproduced ventilation conditions and modeled aerosol dispersion and inter-room particle transport. Genomic sequencing identified transmission links that were not fully explained by contact tracing alone. CFD simulations showed consistent aerosol recirculation between patient rooms and corridors, with localized increases in particle concentrations in poorly ventilated areas due to an extraction failure. Spatial overlap between airflow pathways and genetically linked cases supported the plausibility of airborne transmission and helped explain differences in outbreak magnitude over time. Combining CFD modeling with viral genomic sequencing provided complementary insights into airborne transmission pathways not fully captured by conventional epidemiologic investigation and can guide targeted ventilation interventions.
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