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

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 hr), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10 µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 hr). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.

Infection- or AZD1222 vaccine-mediated immunity reduces SARS-CoV-2 transmission but increases Omicron competitiveness in hamsters.

Limited data is available on the effect of vaccination and previous virus exposure on the nature of SARS-CoV-2 transmission and immune-pressure on variants. To understand the impact of pre-existing immunity on SARS-CoV-2 airborne transmission efficiency, we perform a transmission chain experiment using naïve, intranasally or intramuscularly AZD1222 vaccinated, and previously infected hamsters. A clear gradient in transmission efficacy is observed: Transmission in hamsters vaccinated via the intramuscular route was reduced over three airborne chains (approx. 60%) compared to naïve animals, whereas transmission in previously infected hamsters and those vaccinated via the intranasal route was reduced by 80%. We also find that the Delta B.1.617.2 variant outcompeted Omicron B.1.1.529 after dual infection within and between hosts in naïve, vaccinated, and previously infected transmission chains, yet an increase in Omicron B.1.1.529 competitiveness is observed in groups with pre-existing immunity against Delta B.1.617.2. This correlates with an increase in the strength of the humoral response against Delta B.1.617.2, with the strongest response seen in previously infected animals. These data highlight the continuous need to improve vaccination strategies and address the additional evolutionary pressure pre-existing immunity may exert on SARS-CoV-2.

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

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 h), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 h). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.

Infection- or vaccine mediated immunity reduces SARS-CoV-2 transmission, but increases competitiveness of Omicron in hamsters.

Omicron has demonstrated a competitive advantage over Delta in vaccinated people. To understand this, we designed a transmission chain experiment using naïve, 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 naïve 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.