Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection

Abstract

Emerging highly pathogenic coronaviruses (CoV) are a global public health threat due to the potential for person-to-person transmission and higher mortality rates than common seasonal respiratory pathogens. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing lethal respiratory disease in approximately 35% of human cases.Primate models of highly pathogenic coronavirus infection are needed to support development of therapeutics or vaccines, but few models exist that recapitulate severe disease signs. For initial development of a MERS-CoV primate model, twelve African green monkeys (AGMs) were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. We observed a dose- dependent increase of respiratory disease signs and viral titers in serum and throat swabs between the 103 PFU and the 105 PFU dose groups, although all AGMs survived for the 28 day duration of the study. This study is the first to describe dose-dependent effects of highly pathogenic coronavirus infection of primates and uses a route of infection (small particle aerosol) with potential relevance to MERS-CoV transmission in humans. Aerosol exposure of AGMs may provide a platform for the development of primate models of novel coronavirus disease, with potential utility in therapeutic development and viral pathogenesis studies.

Factors associated with asymptomatic infection in health-care workers with severe acute respiratory syndrome coronavirus 2 infection in Wuhan, China: a multicentre retrospective cohort study

“…In 12 African green monkeys exposed to different target doses of aerosolized MERS-CoV, a dose-dependent increase of respiratory disease signs was observed. 26 In our study, we firstly showed that tracheal intubation or extubation were associated an increased likelihood of symptomatic SARS-CoV-2 infection. One possible explanation could be that a relatively high initial virus exposure might lead a high viral load in respiratory tract, thereby overcoming the barriers of the immune responses and causing symptomatic infection or even unfavorable disease outcome.…”

Slight reduction in SARS-CoV-2 exposure viral load due to masking results in a significant reduction in transmission with widespread implementation

“…We project that masks will lead to a lower exposure viral load among newly infected people, particularly if both the transmitter and exposed individual are successfully masked. Animal models of SARS-CoV-1 and MERS (27,28,34), as well as challenge studies with influenza H1N1 in humans (35), all demonstrate that lower exposure dose is associated with less severe disease, and human data from the Hong Kong SARS-CoV-1 outbreak in Hong Kong suggest a similar trend (36). While data for SARS-CoV-2 in humans is lacking, it is notable that age-adjusted hospitalization and death rates may be decreasing since more widespread utilization of masks.…”

“…Another theoretical benefit of masks is reduction in exposure viral load which in animal models of SARS-CoV-1 and MERS, leads to less severe infection (26)(27)(28). Simulating under the assumption that 75% of people wear masks 75% of the time (i.e., a situation representing current levels of masking in the United States), we identified that viral load of a transmitter required to generate secondary infections increases slightly with higher implementation of more efficacious masks, particularly with dual masking of transmitters and exposed contacts (Fig 8a).…”

Animals and SARS-CoV-2: Species susceptibility and viral transmission in experimental and natural conditions, and the potential implications for community transmission.

“…Study authors concluded that the experimental non-human primate species tested are permissive to SARS-CoV-2 infection, shed virus for pronged periods of time and display COVID-19-like disease, thereby providing suitable animal models for COVID-19 studies (Munster et al, 2020;Totura et al, 2020).…”