ABSTRACT
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.
ABSTRACT
Omicron has demonstrated a competitive advantage over Delta in vaccinated people. To understand this, we designed a transmission chain experiment using naive, intranasally (IN) or intramuscularly (IM) vaccinated, and previously infected (PI) hamsters. Vaccination and previous infection protected animals from disease and virus replication after Delta and Omicron dual challenge. A gradient in transmission blockage was observed: IM vaccination displayed moderate transmission blockage potential over three airborne chains (approx. 70%), whereas, IN vaccination and PI blocked airborne transmission in >90%. In naive hamsters, Delta completely outcompeted Omicron within and between hosts after dual infection in onward transmission. Although Delta also outcompeted Omicron in the vaccinated and PI transmission chains, an increase in Omicron competitiveness was observed in these groups. This correlated with the increase in the strength of the humoral response against Delta, with the strongest response seen in PI animals. These data highlight the continuous need to assess the emergence and spread of novel variants in populations with pre-existing immunity and address the additional evolutionary pressure this may exert on the virus.
ABSTRACT
To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against conserved/relatively-occluded, rather than variable/immunodominant/exposed, epitopes. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicron and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.
ABSTRACT
An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, a non-transgenic model that develops severe acute respiratory disease has not been described. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding for nonstructural protein 6 in open reading frame 1a/1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID19 and as such, are uniquely suited to test viral countermeasures. One Sentence SummarySARS-CoV-2 infected mink develop severe respiratory disease that recapitulates some components of severe acute respiratory disease, including ARDS.
