SARS-CoV-2 aerosols: A physical bridge linking upper respiratory infection to lung pathology — A pathological transmission hypothesis

• Proposes aerosols as a physical bridge linking the upper to lower respiratory tract via exogenous seeding and re-inhalation of self-generated virus-containing aerosols. • Presents a hypothesis-generating “Three-Tier Physical Gradient” in early COVID-19 CT abnormalities across ventilation conditions. • Highlights environment-dependent URT–LRT dissociation despite high upper-respiratory viral loads. • Suggests fine-aerosol control in enclosed settings may selectively reduce pulmonary pathology beyond transmission prevention SARS-CoV-2 infection shows a dichotomy: upper respiratory tract (URT) replication is common, whereas lower respiratory tract (LRT) involvement largely determines whether illness remains URT-limited or progresses toward pneumonia. Yet mechanisms linking URT infection to early, multifocal lung involvement remain unclear. Early COVID-19 chest computed tomography (CT) often shows rapid, multifocal, peripherally distributed ground-glass opacities (GGOs), and imaging involvement varies by environment and exposure route: in a high-containment human challenge trial (HCT), volunteers developed high URT viral loads but rarely showed CT abnormalities while isolated in individual negative-pressure rooms. We propose a “pathological transmission” hypothesis in which virus-laden aerosols provide a physical bridge from URT to lung via (i) exogenous seeding and (ii) re-inhalation of self-generated virus-containing aerosols under low-dilution indoor conditions. A secondary synthesis of early-pandemic cohorts suggests a hypothesis-generating, stepwise “Three-Tier Physical Gradient” in CT abnormality (any): Tier 1 household/community settings, 84% overall (Shanghai mass screening) and 68% among pooled asymptomatic cohorts; Tier 2 coarse filtration/partial recirculation (Diamond Princess), 61% overall and 54% asymptomatic; Tier 3 individual negative-pressure rooms (UK HCT), 11%. This pattern is compatible with modulation of LRT imaging involvement by air-handling conditions rather than inevitable within-host spread. The hypothesis motivates testing whether disrupting fine-aerosol accumulation in enclosed, accumulation-prone public and private microenvironments can reduce LRT involvement even when URT infection is established.