RAPID: Aerosol and Direct Transmission of SARS-CoV-2 in Bats and other Animals

This research will increase our understanding of the transmission of SARS-CoV-2 between species, focusing on bats, hamsters, and deer mice. This knowledge is urgently needed because the SARS-CoV-2 coronavirus is causing the COVID-19 pandemic and is being spread rapidly and globally by humans. It is therefore coming into contact with many potential novel hosts. This is problematic for a number of reasons: (1) novel hosts could serve as intermediate or amplifying hosts in which viral mutations occur that impact efficiency for zoonotic transmission or pathogenesis, (2) novel hosts could become new reservoirs for the virus, (3) there could be a heavy disease toll on the hosts with major economic ramifications if they are livestock, or with ecological ramifications if they are wildlife, and (4) infection of more hosts, including potential spillback to bats, increases the chances of genesis of yet more novel coronaviruses. It is known that SARS-CoV mutated over the 2002-2004 epidemic to become more virulent. It is likely there will be recurrent waves of SARS-CoV-2 with altered virulence as it spreads globally. It is therefore critically important to increase our knowledge about the transmission of SARS-CoV-2 between species. Knowledge of routes of infection will help prevent transmission and can influence the clinical outcome of diseases. This research also will provide an exceptional interdisciplinary training opportunity for a postdoctoral fellow.

This research will examine why transmission of SARS-CoV-2 occurs by a fecal-oral route in some animals, such as bats, but can be airborne in others, such as hamsters, deer mice and humans. The project will lead to a better understanding of why the lungs of bats remain uninfected when the respiratory system is exposed to the virus by inhalation. Insufflated particles may be filtered in the upper airways, lung cells may lack the cellular machinery required for viral entry [angiotensin-converting enzyme-2 (ACE2) receptors and the serine protease TMPRSS2], or the virus may enter cells but not replicate within them. The following experiments will be conducted in bat, hamster, and deer mice that are inoculated by direct contact or by insufflation of viral laden aerosol: (1) Regions within the respiratory system where insufflated aerosolized particles are most likely to be deposited during breathing will be modeled using computational fluid dynamics. (2) Maps of cells that express ACE2, TMPRSS2, and viral RNA within the respiratory system and the small intestine will be generated using RNAscope. (3) These maps will be compared to measurements of viral protein assayed with immunohistochemistry. In addition to new knowledge about SARS-CoV-2 transmission, this project will provide basic information about lung physiology and cell biology in three mammal species, and will provide interdisciplinary training for a post-doctoral fellow.

This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.