From exhalation to infection: A multiscale review of infectious respiratory particle dynamics

Infectious respiratory particles (IRPs) are the dominant vehicle for airborne transmission of respiratory viruses, yet their complete life cycle (from formation inside the human body to deposition and host cell infection) remains insufficiently integrated for quantitative risk assessment. Here, we synthesize 238 studies to provide the first integrated, multiscale appraisal of IRP fate from airway formation to post-deposition virus–host interactions. We consolidate a comprehensive numerical framework that couples computational fluid dynamics (CFD) with virus dynamics (VD) models to trace IRPs across physiological and environmental scales. Current evidence indicates that IRPs are generated primarily in the oral cavity, larynx, trachea, and terminal bronchioles through four distinct mechanisms. Exhaled size distributions are tightly linked to respiratory activity and anatomical origin, whereas temperature, humidity, initial velocity, and indoor airflow govern size evolution and trajectory during transport. Increased salinity or inlet humidity, or reduced inlet temperature, enhances hygroscopic growth of IRPs, enlarging their particle diameter and promoting deposition in the upper respiratory tract. CFD–VD coupling markedly improves the accuracy of predicting in vivo viral infection. Finally, we identify critical knowledge gaps are the absence of standardized composition models of IRPs and limited validation of IRP deposition within the human body. New methods and technologies need to be developed to measure their precise composition and deposition. Concurrently, integrating machine learning algorithms shows significant potential for rapidly tracking IRPs and predicting clinical infection status, which may provide targeted information for the prevention and treatment of infectious respiratory diseases.