Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 via Close Contact and Respiratory Droplets Among Human Angiotensin-Converting Enzyme 2 Mice

Abstract

We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations.

Keywords: SARS-COV-2; aerosol; close contact; hACE2 transgenic mice; respiratory droplets; transmission routes.

Figure 1.

Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among human angiotensin-converting enzyme 2 (hACE2) transgenic mice via different routes. A, Graphic outline of experimental design and sample collection. B, The changes in body weight in the 3 hACE2 mice intranasally inoculated with 5 × 10⁵ median tissue-culture infectious dose (TCID₅₀) of SARS-CoV-2 used to measure close-contact transmission. C, Changes in body weight in the 13 naive hACE2 mice after they were introduced into the same cage with infected mice. D, Reactivity of the serum samples from the 13 cohoused mice with SARS-CoV-2 antigens. E, Changes in body weight in the other 3 hACE2 mice intranasally inoculated with 5 × 10⁵ TCID₅₀ of SARS-CoV-2 used to measure the respiratory droplets transmission. F, Changes in body weight in the 10 naive hACE2 mice after introduced into the same cage separated by 2 layers of stainless-steel grids with the infected mice. G, Reactivity of the serum samples from the 10 mice for respiratory droplets experiment with SARS-CoV-2 antigens. H, Histopathological observation of the hACE2 mice inoculated with aerosol for different durations. Abbreviations: IgG, immunoglobulin G; OD₄₅₀, optical density at 450 nm.