Wednesday, May 03, 2023

Preprint: Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron Variants in Mice and Hamsters

(From Preprint)


Although hopes are growing that after three long years our COVID crisis may be winding down, new variants continue to emerge, leaving many unknowns regarding the future trajectory and impact of the SARS-CoV-2 virus. 

While exquisitely adapted to humans, SARS-CoV-2 has also found a plethora of other suitable hosts, including mink, deer, dogs, cats, and even rodents (see Nature: Comparative Susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV Across Mammals).

The concern is that the virus might adapt to another species, follow a divergent evolutionary path, only to `spill back' into humans as a `new', and potentially more dangerous, threat. 

And the reality is, we've already seen that happen.

In late 2020, Danish authorities announced the spillover of COVID into millions of susceptible farmed mink, and the discovery of several `mink specific' mutations in the virus (see Denmark Orders Culling Of All Mink Following Discovery Of Mutated Coronavirus)which subsequently jumped back into the human population.

Although this `mink variant' was quickly supplanted by the Alpha variant - it serves as a `proof of concept' that - if allowed to spread in a non-human species, SARS-CoV-2 has the ability to evolve into something `new' and spill back into humans.

While controversial, there is even some evidence to suggest that the Omicron variant may have evolved after the virus jumped to mice or other rodents (see Evidence for a mouse origin of the SARS-CoV-2 Omicron variant), and then spilled back into humans. 

For more on this, see Maryn McKenna's Wired article Where Did Omicron Come From? Maybe Its First Host Was Mice. 

When the pandemic began, however, mice appeared largely immune to the coronavirus. But two years ago in PrePrint: The B1.351 and P.1 Variants Extend SARS-CoV-2 Host Range to Mice, we learned hat some SARS variants had overcome that barrier.

Six months ago, in Preprint: SARS-CoV-2 Infection in Domestic Rats After Transmission From Their Infected Ownerwe saw further evidence of the susceptibility of rodents to COVID, with the author's writing:

We report the transmission of SARS-CoV-2 Omicron variant from a COVID-19 symptomatic individual to two domestic rats, one of which developed severe symptoms. Omicron carries several mutations which permit rodent infection. This report demonstrates that pet, and likely wild, rodents could therefore contribute to SARS-CoV-2 spread and evolution.

. . . . our results indicate that rats are susceptible to infection with Alpha, Delta, and Omicron variants, and wild Norway rats in the NYC municipal sewer systems have been exposed to SARS-CoV-2. Our findings highlight the need for further monitoring of SARS-CoV-2 in urban rat populations and for evaluating the potential risk of secondary zoonotic transmission from these rat populations back to humans.

While this study found that Alpha, Delta, and Omicron variants could all infect rats, the Delta variant displayed the highest infectivity. 

We a new preprint today from researchers at Washington University School of Medicine (St. Louis) that suggests that newer BQ.1.1 Omicron variants may be better adapted to some rodent species than earlier (BA.5.5) Omicron variants. 

The full report runs 29 pages, so I've just reproduced the Abstract and Importance section below. Follow the link to read it in its entirety.  I'll have a brief postscript when you return. 

James Brett Case, Suzanne M Scheaffer, Tamarand L Darling, Traci L Bricker, Lucas J Adams, Houda H. Harastani, Reed Trende, Shilpa Sanapala, Daved H Fremont, Adrianus C M Boon, Michael S Diamond

Preview PDF


The continued evolution and emergence of novel SARS-CoV-2 variants has resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a currently circulating SARS-CoV-2 Omicron lineage variant, BQ.1.1, in multiple rodent models including K18-hACE2 transgenic, C57BL/6J, and 129S2 mice, and Syrian golden hamsters.

In contrast to a previously dominant BA.5.5 Omicron variant, inoculation of K18-hACE2 mice with BQ.1.1 resulted in a substantial weight loss, a characteristic seen in pre-Omicron variants

BQ.1.1 also replicated to higher levels in the lungs of K18-hACE2 mice and caused greater lung pathology than the BA.5.5 variant. However, C57BL/6J mice, 129S2 mice, and Syrian hamsters inoculated with BQ.1.1 showed no differences in respiratory tract infection or disease compared to animals administered BA.5.5. Airborne or direct contact transmission in hamsters was observed more frequently after BQ.1.1 than BA.5.5 infection. 

Together, these data suggest that the BQ.1.1 Omicron variant has increased virulence in some rodent species, possibly due to the acquisition of unique spike mutations relative to other Omicron variants.


As SARS-CoV-2 continues to evolve, there is a need to rapidly assess the efficacy of vaccines and antiviral therapeutics against newly emergent variants. To do so, the commonly  used animal models must also be reevaluated. Here, we determined the pathogenicity of the circulating BQ.1.1 SARS-CoV-2 variant in multiple SARS-CoV-2 animal models including transgenic mice expressing human ACE2, two strains of conventional laboratory mice, and Syrian hamsters.

While BQ.1.1 infection resulted in similar levels of viral burden and clinical disease in the conventional laboratory mice tested, increases in lung infection were detected in human ACE2-expressing transgenic mice, which corresponded with greater levels of pro inflammatory cytokines and lung pathology.

Moreover, we observed a trend towards greater animal-to-animal transmission of BQ.1.1 than BA.5.5 in Syrian hamsters. Together, our data highlight important differences in two closely related Omicron SARS-CoV-2 variant strains and provide a foundation for evaluating countermeasures.

          (Continue . . . ) 

Two weeks ago, in Eurosurveillance: Cryptic SARS-CoV-2 Lineage Identified on Two Mink Farms In Poland, we looked at a concerning report of two outbreaks of a previously unknown COVID variant on mink farms in Poland, which may have been circulating in an unknown or undetected animal reservoir.

The identity of this host isn't known, although wild mink, cats, dogs, rodents, or other peridomestic mammals are all possibilities.

Last November, a preprint (see Wildlife Exposure to SARS-CoV-2 Across a Human Use Gradient) found evidence of SARS-CoV-2 infection across a wide variety of small peridomestic mammals (e.g. possums, skunks, squirrels, etc.) in Virginia.  

Whether it is in raccoons, squirrels, skunks, or rodents - an expanding host range could provide the virus with more opportunities to reinvent itself.

Which is why we may yet see more COVID-related surprises in the months, and years, to come.