Delving into the replication kinetics of omicron/B.1.1.529 a little further...
Very preliminary work from a preprint of a live and pseudovirus study (Imperial, Pirbright) that indicates that omicron replicates much faster than delta/B.1.617.2 (and AY.4.2), and indeed outcompetes it in human nasal epithelial cells (upper respiratory tract), but omicron entry/replication is otherwise relatively attenuated in other cell line types (lung, ie lower respiratory tract).
Through flow cytometry they determined that (as shown in other studies) omicron continues to use ACE2 for cell entry rather than other receptors, and indeed it binds to human ACE2 to a greater extent than delta or alpha/B.1.1.7 spike.
View attachment 304247 View attachment 304248
They reproduced results from other recent studies suggesting cell surface fusion of omicron, and thus syncytia formation, is greatly reduced compared to previous variants. Quite possibly this reduction in fusogenicity is down to epistatic interactions elsewhere in spike (ie how all the changes in spike play together) as similar S1/S2 adjacent 'point mutations' (notably N679K and P681H) in other variants have heretofore enhanced cleavage.
Using a pseudovirus assay they determined that omicron spike is more able to enter cells expressing ACE2 from a wider range of species than reported for previous SARS-CoV-2 variants. In particular, rat, horseshoe bat, mice and some birds. This could suggest an increased propensity for reverse zoonosis and likelihood of establishing animal reservoirs in those species (though undoubtably there are additional complicating factors associated with the biology, behavioural and environmental circumstances of each species that could either hinder or promote this being realised in each case).
View attachment 304250
Next, using an assay to measure pseudovirus entry into different cell lines they investigated cell entry pathways. Omicron pseudovirus most efficiently entered cells lacking TMPRSS2 expression and, compared to previous VOCs, was less dependent on cells that express abundant TMPRSS2. They demonstrated that omicron spike is sensitive to innate inhibitors of endosomal entry, suggesting this is a preferred route for this particular variant.
Finally, using live virus in primary human airway cells they saw omicron replicate more rapidly than delta. Additionally, a TMPRSS2 inhibitor blocked delta replication but had no effect on omicron. They suggest that omicron can avoid the anti-viral effects of interferon-induced restriction factors which are features of innate immunity, which would otherwise disadvantage endosomal entry (a cell entry pathway not exploited by previous VOC).
View attachment 304249
The study authors propose that omicron has become more generalised, being able to infect a larger number of upper airway cells, and suggest that perhaps it requires a lower infectious dose as a consequence.
Preprint pending.