Host and viral determinants of airborne transmission of SARS-CoV-2 in the Syrian hamster

Airborne transmission is one of the major routes contributing to the spread of SARS-CoV-2. Successful aerosol transmission occurs when people release respiratory particles carrying infectious virus in the fine aerosol size range. It remains poorly understood how infection influences the physiological host factors that are integral to this process. Here we assessed the changes in breathing, exhaled droplets, and released virus early after infection with the Alpha and Delta variants in the Syrian hamster. Infection with the two variants led to only nuanced differences in viral tissue titers, disease severity, or shedding magnitude. Both variants led to a short window of detectable virus in the air between 24 h and 48 h, which was poorly reflected by upper respiratory shedding measured in oropharyngeal swabs. The loss of viable air samples coincided with changes in airway constriction as measured by whole body plethysmography, and a decrease of fine aerosols produced in the 1-10 m aerodynamic diameter range. We found that male sex was associated with greater viral replication in the upper respiratory tract and virus shedding in the air. This coincided with an exhaled particle profile shifted towards smaller droplets, independent of variant. Transmission efficiency of Alpha and Delta did not differ on average but exhibited clear variation among donor individuals, including a superspreading event. Transmission leading to substantial dual infections only occurred when both viruses were shed by the same donor and exposure was prolonged. These findings provide direct experimental evidence that quantitative and qualitative assessment of exhaled aerosols may be critical for understanding the limitations and determinants of efficient airborne transmission, thus allowing us to control the pandemic with non-pharmaceutical interventions. SignificanceAirborne transmission is one of the major routes for SARS-CoV-2, however underlying host and virus parameters remain poorly understood. Here, we provide direct experimental evidence that the quantitative and qualitative assessment of exhaled aerosols are critical to understand the efficiency of SARS-CoV-2 airborne transmission. We show that after infection, the Alpha and Delta variants of concern displayed a short window of detectable virus in the air in contrast to prolonged shedding measured in oropharyngeal swabs. The limited window coincided with changes in airway constriction, and a sex dependent decrease of fine aerosols produced in the 1-10 m aerodynamic diameter range. Dual airborne infections only occurred when both viruses were shed by the same donor and after prolonged exposure.

SARS-CoV-2 disease severity and transmission efficiency is increased for airborne but not fomite exposure in Syrian hamsters

Transmission of SARS-CoV-2 is driven by contact, fomite, and airborne transmission. The relative contribution of different transmission routes remains subject to debate. Here, we show Syrian hamsters are susceptible to SARS-CoV-2 infection through intranasal, aerosol and fomite exposure. Different routes of exposure presented with distinct disease manifestations. Intranasal and aerosol inoculation caused more severe respiratory pathology, higher virus loads and increased weight loss. Fomite exposure led to milder disease manifestation characterized by an anti-inflammatory immune state and delayed shedding pattern. Whereas the overall magnitude of respiratory virus shedding was not linked to disease severity, the onset of shedding was. Early shedding was linked to an increase in disease severity. Airborne transmission was more efficient than fomite transmission and dependent on the direction of the airflow. Carefully characterized of SARS-CoV-2 transmission models will be crucial to assess potential changes in transmission and pathogenic potential in the light of the ongoing SARS-CoV-2 evolution.

The effect of temperature and humidity on the stability of SARS-CoV-2 and other enveloped viruses

Environmental conditions affect virus inactivation rate and transmission potential. Understanding those effects is critical for anticipating and mitigating epidemic spread. Ambient temperature and humidity strongly affect the inactivation rate of enveloped viruses, but a mechanistic, quantitative theory of those effects has been elusive. We measure the stability of the enveloped respiratory virus SARS-CoV-2 on an inert surface at nine temperature and humidity conditions and develop a mechanistic model to explain and predict how temperature and humidity alter virus inactivation. We find SARS-CoV-2 survives longest at low temperatures and extreme relative humidities; median estimated virus half-life is over 24 hours at 10 {degrees}C and 40 % RH, but approximately 1.5 hours at 27 {degrees}C and 65 % RH. Our mechanistic model uses simple chemistry to explain the increase in virus inactivation rate with increased temperature and the U-shaped dependence of inactivation rate on relative humidity. The model accurately predicts quantitative measurements from existing studies of five different human coronaviruses (including SARS-CoV-2), suggesting that shared mechanisms may determine environmental stability for many enveloped viruses. Our results indicate scenarios of particular transmission risk, point to pandemic mitigation strategies, and open new frontiers in the mechanistic study of virus transmission.

K18-hACE2 mice develop respiratory disease resembling severe COVID-19

SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Taken together, this suggests that this mouse model can be useful for studies of pathogenesis and medical countermeasure development. Authors SummaryThe disease manifestation of COVID-19 in humans range from asymptomatic to severe. While several mild to moderate disease models have been developed, there is still a need for animal models that recapitulate the severe and fatal progression observed in a subset of patients. Here, we show that humanized transgenic mice developed dose-dependent disease when inoculated with SARS-CoV-2, the etiological agent of COVID-19. The mice developed upper and lower respiratory tract infection, with virus replication also in the brain after day 3 post inoculation. The pathological and immunological diseases manifestation observed in these mice bears resemblance to human COVID-19, suggesting increased usefulness of this model for elucidating COVID-19 pathogenesis further and testing of countermeasures, both of which are urgently needed.