From SARS-CoV-2 infection to COVID-19 disease: a proposed mechanism for viral spread to the lower airway based on in silico estimation of virion flow rates

Abstract

ABSTRACTWhile the nasopharynx in the upper respiratory airway is the dominant initial infection site for SARS-CoV-2, the physiologic mechanism that launches the infection in the lower airway is still not well-understood. Based on the rapidity with which SARS-CoV-2 infection progresses to the lungs, it has been conjectured that the nasopharynx acts as the seeding zone for subsequent contamination of the lower airway via aspiration of virus-laden boluses of nasopharyngeal fluids. In this study, we examine the plausibility of this proposed mechanism. To this end, we have developed computational fluid mechanics models of the inhalation process in two medical imaging based airway reconstructions and have quantified the nasopharyngeal liquid volume ingested into the lower airspace during each aspiration. The numerical predictions are validated by comparing the number of projected aspirations (approximately 2 – 4) during an eight-hour sleep cycle with prior observational findings of 3 aspirations in human subjects. Extending the numerical trends on aspiration volume to earlier records on aspiration frequency for the entire day indicates a total aspirated nasopharyngeal liquid volume of 0.3 – 0.76 ml per day. We then used sputum assessment data from hospitalized COVID-19 patients to estimate the number of virions that are transmitted daily to the lungs via nasopharyngeal liquid boluses. For mean sputum viral load, our modeling projects that the number of virions penetrating to the lower airway per day will range over 2.1 × 106 – 5.3 × 106; for peak viral load, the corresponding number of penetrating virions hovers between 7.1 × 108 – 17.9 × 108. These findings fill in a key piece of the mechanistic puzzle of the progression from SARS-CoV-2 infection of the nasopharynx to the development of COVID-19 disease within a patient, and point to dysphagia as a potential underlying risk factor for COVID-19. The findings also have significant practical implications in the design of COVID-19 prophylactics and therapeutics that aim to constrain the pathogenic progress of the disease within the limits of the upper airway.