In evolving to infect mink, SARS-CoV-2’s risk for humans changes

Computer generated graphical representation of the coronavirus.
Enlarge / The coronavirus spike protein that mediates coronavirus entry into host cell.

We’ve always needed to limit the total SARS-CoV-2 infections for reasons beyond the immediate risk they pose to the infected. Each new infected individual is a chance for the virus to evolve in a way that makes it more dangerous—more infective or more lethal. This is true even when an individual has a completely symptom-free infection. The more the virus replicates, the more mutations it will experience and the greater chance that something threatening will evolve.

One of the disturbing discoveries of the past year has been that it’s not just the human population we have to worry about. SARS-CoV-2 has been found in a number of species, notably cats and mink, that we spend a lot of time around. It has even spread from there to the wild mink population, and the virus has jumped back and forth between humans and farmed mink. These animal reservoirs provide added opportunities for COVID to evolve in ways that make it more dangerous to us—perhaps via mutations that allow it to adapt to the new species.

A group of German researchers has now tested some of the mutations that have appeared in viruses circulating in mink populations, and the news is mixed. One specific mutation makes the virus somewhat less infectious to humans but reduces the probability that antibodies raised against the virus will recognize it.

A bit different

When we first reported on the virus appearing in mink, all we really knew was that it picked up mutations while infecting the animals; we were still too early to even put together a list of mutations commonly seen in mink. That has now changed, and the research team has a list to work with; there’s now a catalog of mutations found in European mink farms but not circulating in humans. The researchers focused on mutations in the Spike protein, which the virus uses to latch on to human cells and infect them. Spike is important both because it determines which cells the virus can infect, and it’s often the target of antibodies that can block the virus from entering cells.

To look into these mutations, the researchers engineered different versions of the Spike protein into a harmless virus and tested whether the engineered virus could infect cells. They found that certain mutations made it harder for Spike to get the virus into some human cells. There were still some types of human cells it could infect—notably intestine and lung cells, two major sites of SARS-CoV-2 infection. But the virus had a harder time infecting others.

Separately, the researchers looked at how these mutations fared against the antibody response mounted after SARS-CoV-2 infection using serum obtained from 14 people who had been infected previously. They focused on a single mutation located in the part of the Spike protein that latches on to the surface of human cells (as opposed to the part that opens up the cells’ membrane).

All but one of the 14 serum samples were able to block infection by the engineered virus without any Spike mutations. But all the sera were less effective at blocking infections by viruses that carried a Spike protein altered by a single mutation found in mink. All of them could still block the virus; it just took more serum to do so.

Looking into this more carefully, the researchers checked the two antibodies used in a potential COVID-19 therapy made by Regeneron. Either of these antibodies is capable of blocking infection of cultured human cells by SARS-CoV-2 on their own. But when tested against Spike carrying the mutation found in mink, only one of the two antibodies still neutralized it. Again, this is consistent with the mutation altering Spike’s profile from the immune system’s perspective.

What does this mean?

The specific mutation that alters the immune response has also been seen in strains that have adapted to circulate in ferrets, and it’s at a location that physically interacts with a human protein. So, in all likelihood, this mutation has been selected for enabling more efficient infection of mink. By contrast, the mutation has rarely been seen in humans—just one report of it being found in a person with a persistent infection.

The same virus seems to infect human cells somewhat less well. This suggests that current adaptations to mink don’t seem to make the virus more dangerous to humans in this regard, although we can’t rule out that further evolution won’t have different implications for humans.

Potentially more concerning is the virus’s reduced immune profile. We’ve designed antibodies that block the virus for use as therapies, and we use them as a measure of an effective immune response. So changes there are obviously attention-grabbing.

That said, the ability of antibodies to block Spike is reduced, not eliminated. And we’re still not certain about the relative importance of neutralizing antibodies relative to other aspects of the immune response. So, while it sounds really bad, it may not have a significant effect on the virus’s transmissibility in humans. In the end, we’re probably more at risk of variants that evolve in humans, where they’re exposed to the actual human immune response.

Still, the study reinforces a more general worry about management of the pandemic. The virus has spread so widely that it’s no longer a matter of simply getting it under control in the human population. We now also have to be aware of the risk of the virus spreading back to us from one of the domesticated species we’ve transferred it to.

Cell Reports, 2021. DOI: 10.1016/j.celrep.2021.109017  (About DOIs).