Modeling SARS-CoV-2 propagation using rat coronavirus-associated shedding and transmission

Abstract

At present, global immunity to SARS-CoV-2 resides within a heterogeneous combination of susceptible, naturally infected and vaccinated individuals. The extent to which viral shedding and transmission occurs on re-exposure to SARS-CoV-2 is an important determinant of the rate at which COVID-19 achieves endemic stability. We used Sialodacryoadenitis Virus (SDAV) in rats to model the extent to which immune protection afforded by prior natural infection via high risk (inoculation; direct contact) or low risk (fomite) exposure, or by vaccination, influenced viral shedding and transmission on re-exposure. On initial infection, we confirmed that amount, duration and consistency of viral shedding, and seroconversion rates were correlated with exposure risk. Animals were reinfected after 3.7–5.5 months using the same exposure paradigm. 59% of seropositive animals shed virus, although at lower amounts. Previously exposed seropositive reinfected animals were able to transmit virus to 25% of naive recipient rats after 24-hour exposure by direct contact. Rats vaccinated intranasally with a related virus (Parker’s Rat Coronavirus) were able to transmit SDAV to only 4.7% of naive animals after a 7-day direct contact exposure, despite comparable viral shedding. Cycle threshold values associated with transmission in both groups ranged from 29–36 cycles. Observed shedding was not a prerequisite for transmission. Results indicate that low-level shedding in both naturally infected and vaccinated seropositive animals can propagate infection in susceptible individuals. Extrapolated to COVID-19, our results suggest that continued propagation of SARS-CoV-2 by seropositive previously infected or vaccinated individuals is possible.

Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data

“…Mixing interactions characterizing infectious disease transmission in human populations are heterogeneous, complex, and dynamic ( 76 , 77 ). Because the full spectrum of these cannot be feasibly modeled in animals, we assessed immune heterogeneity and duration associated with infection and reinfection via high and low risk exposure routes ( 14 ). Beginning with a defined SDAV inoculum, we established initial infection using high risk (H: cohabitation) and low risk (L: fomite) transmission to mimic heterogeneous viral exposure in a naturally infected population ( 14 ).…”

“…Because the full spectrum of these cannot be feasibly modeled in animals, we assessed immune heterogeneity and duration associated with infection and reinfection via high and low risk exposure routes ( 14 ). Beginning with a defined SDAV inoculum, we established initial infection using high risk (H: cohabitation) and low risk (L: fomite) transmission to mimic heterogeneous viral exposure in a naturally infected population ( 14 ). In the high-risk (H) group, cohabiting animals experienced short-range viral exposure through direct physical contact, aerosol, or droplet routes ( 34 , 78 , 79 ).…”

“…Experimental design and outcomes have been previously published ( 14 ) and are briefly summarized here. Young adult Sprague–Dawley rats, evenly split by sex, were infected as follows:…”

“…In this paper, we develop compartmental models of COVID-19 pandemic to endemic transition using parameter estimates derived from controlled coronaviral infection study in rats ( 14 ). Sialodacryoadenitis virus (SDAV) is a highly infectious betacoronavirus ( 2 , 9 , 15 ) that causes transient respiratory disease in rats ( 16 , 17 ).…”

Wastewater Surveillance of U.S. Coast Guard Installations and Seagoing Military Vessels to Mitigate the Risk of COVID-19 Outbreaks

“…Further confounding variables are that the amount of SARS-CoV-2 shedding by individuals is variable over the course of their infection. Also, different individuals shed different amounts of virus depending, potentially, on the severity of their infection, their vaccination status, and whether they've had a prior infection (Zeiss, Asher, Vander Wyk, Allore, & Compton, 2021).…”