Abstract
The incidence of severe COVID-19 in children is low, and underlying mechanisms for lower SARS-CoV-2 susceptibility and self-limiting disease severity are poorly understood. Severe clinical manifestations in adults require SARS-CoV-2 inoculation in the lower respiratory tract, establishing a pulmonary disease phase. This may be either accomplished by direct inoculation of the thoracic region upon exposure to virion-laden aerosols, or by infection of the upper respiratory system and aspiration of virion-laden aerosols originating right there into the lower respiratory tract. The particularities of epithelial barriers as the anatomical site of first viral deposition specifically determine the initial characteristics of an innate immune response, emerging respiratory tissue damage and dysfunctionality, and hence, severity of clinical symptoms. We, thus, investigated by in silico modeling whether the combined effect of juvenile lung morphometry, children's ventilatory pattern and the peculiarities of the virion-laden aerosols' properties, render children more resilient to aerosol deposition in the lower respiratory tract. Our study presents evidence for major age-dependent differences of the regional virion-laden aerosol deposition. We identified deposition hotspots in the alveolar-interstitial region of the young adult. Our data reveal that children are void of corresponding hotspots. The inoculum quantum in the alveolar-interstitial region hotspots is found to be considerably related to age. Our results suggest that children are intrinsically protected against SARS-CoV-2 inoculation in the lower respiratory tract, which may help to explain the lower risk of severe clinical manifestations associated with a pulmonary phase.