One thing we’ve been watching for with SARS-CoV-2 in animals is whether we will see establishment of “animal” variants. Humans have done an effective job of infecting a wide variety of animal species with this primarily-human virus. Fortunately, thus far these infections usually die out rapidly in that animal or group of animals (mink being a notable exception). In that scenario, the broader implications of spillover into animals are limited, because there’s not enough long-term transmission for animals to become true reservoirs or for new variants to emerge.

White-tailed deer have been a particular concern lately because they are quite susceptible to infection with SARS-CoV-2, they can spread the virus effectively deer-to-deer, and they live in large enough groups that the virus could potentially be maintained in the deer population even without regular contact with infected people.

Until recently, surveillance of deer for exposure to and infection with SARS-CoV-2 (primarily in the US, but now in Canada as well) yielded a mix of good news and bad news. The good news was that the strains found in deer were the same as those found in people in the same area around the same time. That suggests that transmission was commonly occurring from people to deer, but without evidence of long-term circulation in deer population or mutation of the virus to adapt to deer.

However, there is now new evidence based on a pre-print study from a Canadian research group (Pickering et al. 2022) that the SARS-CoV-2 virus may have been circulating in some deer populations for longer that previously thought, leading to emergence of a divergent strain of the virus.

Here is the (not so) short summary of their findings:

  • Nasal swabs and retropharyngeal lymph nodes (glands located at the back of the throat) were collected from 300 hunter-collected deer in Ontario between November 1 and December 31, 2021.
  • Five (2.3%) nasal swabs and 16 (5.3%) lymph node samples were PCR positive for SARS-CoV-2, for an overall prevalence of 6% in the deer sampled. That’s a low percentage, which is good, and is consistent with some earlier Canadian deer surveillance, though some US studies have reported much higher rates of exposure and infection among deer in some states.
  • All positive deer were from southwestern Ontario.

The good news aspect of the low prevalence is offset by some bad news about the genetic makeup of the viruses that were found. Sequence analysis was only possible for a subset of positive samples. (There can be various reasons for that. Most often, it’s because there’s enough virus to yield a positive PCR result but not enough to be able to get good sequencing data). Using a couple of techniques, they ultimately managed to get full sequence data from 5 samples and partial genomes from 2.  The deer SARS-CoV-2 viruses belonged to the B1 lineage, which encompasses a wide group of common strains. However, the deer samples formed their own group that was very different from other reported sequences in B1 lineage, with the closest “relatives” being sequences from people collected in Michigan in November/December 2020 (where they had also seen spillover into the deer populations there). (See image below, or click here to enlarge image.)

  • We have to be a bit careful when looking at sequence databases because we can only compare “new” strains with sequences that have been deposited. That doesn’t mean these strains don’t exist anywhere else, it just means they haven’t been reported from anywhere else. Yet, given the scope of SARS-CoV-2 surveillance worldwide, it’s supportive of this being a divergent deer-associated lineage.
  • The fact that the most closely related strains of SARS-CoV-2 are from Michigan in 2020 raises a few interesting questions. Michigan is just across the border from Ontario, but it’s not a simply border for deer to cross because of the Great Lakes and associated rivers. There’s no direct land bridge, so it’s not just a matter of a deer wandering across a political border on a map.
  • It was also noted that the November/December 2020 sequences from human samples from Michigan were closely related to  sequences from mink samples from the same state collected in September/October 2020.

This brings up many other questions, such as:

  • Did a “human” strain of SARS-CoV-2 spread from people to deer in Ontario and then mutate, or did deer pick this up from other wildlife?
  • If SARS-CoV-2 is present in other wildlife, which species are of concern and how did they get it?
  • Could this strain be present in wildlife in Michigan and have moved to Ontario via a non-deer wildlife species?

The other question that obviously comes to mind is “Is this strain actually present in people, and this really just represents human-to-deer transmission of a strain we haven’t detected in people?”  That’s a reasonable question but a few things make it less likely.  A strain like this, that is quite divergent genetically, presumably mutated over time to get to where it is. If this had occurred in people, odds are reasonable that sequences from one or more of those intermediary strains would have been identified at some point, even though we don’t sequence the virus from every single human infection. That’s not the case here. That could just reflect variant development in an area where testing was limited, so we can’t dismiss the possibility completely. However, it supports the notion that this strain might have evolved in animals (deer or otherwise).

Potential deer-to-human transmission

Another noteworthy aspect of this report is information about a potential deer-to-human transmission event. One human sample from Ontario from December 2021 was found with most (80 of 90) of the same mutations and was consistent with this deer-group of viruses. It wasn’t possible to say where this strain fit into the timing of viral evolution, i.e. was it a step along the way of the progression to the deer lineage, or was it derived from a deer strain?  The human sample pre-dates the deer sampling, but we have to be careful interpreting timing of deer samples because collection occurs during a defined time of year: hunting season. So, while these strains were first found in deer in samples from November/December 2021, we have to assume that they were present earlier. There’s also a plausible epidemiological link between the infected person and deer, as there was known “close contact” with deer.  Note: that’s contact with deer, not the known-positive deer.  Further details of the “close contact” were not provided.

This gets us back to the “chicken vs egg” discussion.  Did this person get infected from deer, or were they a source of infection for deer?  Until December 2021, virtually all PCR-positive samples in Ontario were being sequenced, so it’s unlikely this strain was emerging in people in a lead up to a spillover into deer. There was less testing (and sequencing) in humans in late 2021 as the omicron surge overwhelmed testing capacity in Ontario.

Have there been more human cases of this strain?

  • That’s hard to say, since this was a very recent observation in deer and the risk of spillback into people was probably most likely during the recent hunting season. Omicron blasted through Ontario at the same time, and there were severe limitations in testing. At that point only a minority of people got tested, particularly of otherwise healthy people from the community (who would be at greatest likelihood of deer exposure). There’s currently no evidence of onward human-to-human spread, but we have to realize that surveillance decisions made by the province impact the ability to detect spread of new variants.

I won’t get much into the genomics themselves, since this post is pretty long and the story above is the key. More details about these new finding are in the paper. However, the quick version is that many of the mutations that were found in the strains from the deer are consistent with those found in animals such as bats, cats, hamsters, mink and, yes, other deer. When a virus jumps to a different host, we can see some more common genetic changes as it adapts to that new species.

Ultimately, to answer these and other questions, we need more samples from deer from different areas and over time, and more comparison with human-derived virus sequences. The current story is based on a small number of samples from a narrow window in time, but the story is pretty compelling and concerning.

If this is truly a deer strain of SARS-CoV-2, what does that mean?

That’s still hard to say. The big question is what happens over time.  Will this strain (or others) be maintained in deer? If so, will deer become a true reservoir, where they can then potentially infect people and other animals?

The “other animals” component is often neglected, but it’s important. If deer are a reservoir, they could spread it to other potential reservoir species, amplifying the problem. They could also spread it to other susceptible species that are not likely to become reservoirs based on numbers and population dynamics, but that have closer contact with people. For example, we’re not going to see a reservoir in domestic cats because there’s not much chance of sustained cat-to-cat spread in most situations. However, cats are highly susceptible and indoor-outdoor cats have abundant contact with wildlife (including deer) so they could plausibly be a bridge from wildlife reservoirs to people.

A closing piece of good news is that it looks like these deer variants are as effectively neutralized by vaccine antibodies as other lineages.

Much of the story here is quite speculative, but it’s why we’ve been talking about the need to study SARS-CoV-2 in animals from the start of the pandemic. Those pleas were largely ignored for a long time, so now we’re playing catch-up. I’d hoped we would be lucky and that our negligence in supporting study of animals wouldn’t come back to bite us in the butt. I’m not as convinced that’s going to be the case now. It’s hard to say if we could have done anything differently if we’d had support to investigate earlier, but it certainly wouldn’t have hurt.

The image below from the preprint article (Pickering et al. 2022) depicts an overview of the potential zoonotic scenarios underpinning the evolution of the SARS-CoV-2 strains in white tailed deer in Ontario, and the one associated human case (click here to enlarge).