We have always had to limit the total number of SARS-CoV-2 infections for reasons that go beyond the immediate risk to those infected. Every new infected individual has a chance for the virus to evolve in a way that makes it more dangerous – more infectious or lethal. This is true even when a person has a completely asymptomatic infection. The more the virus reproduces, the more mutations will be experienced and the greater the chances that something threatening will evolve.
One of the disturbing discoveries of the last year has been that we do not have to worry only about the human population. SARS-CoV-2 has been found in many species, especially cats and minks, which we spend a lot of time around. It spread right from there to the wild mink population, and the virus jumped back and forth between humans and farm mink. These animal tanks provide additional opportunities for COVID to evolve in ways that make it more dangerous to us – perhaps through 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. A specific mutation makes the virus somewhat less infectious to humans, but reduces the likelihood that antibodies raised against the virus will recognize it.
A little different
When I first reported the virus in the mink, all I really knew was that it took over mutations during the infection of the animals; we were still too early to even put together a list of commonly encountered mutations in mink. That has changed now, and the research team has a list to work with; there is 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 attach to human cells and infect them. Spike is important both because it determines which cells can infect the virus and is often the target of antibodies that can block the virus from entering the cells.
To analyze these mutations, the researchers designed different versions of the Spike protein into a harmless virus and tested whether the projected virus could infect cells. They found that certain mutations made it more difficult to introduce the virus into some human cells for Spike. There were still several types of human cells that could infect – especially intestinal and lung cells, two major sites of SARS-CoV-2 infection. But the virus found it harder to infect others.
Separately, the researchers looked at how these mutations evolved against the response to mounted antibodies after SARS-CoV-2 infection using serum obtained from 14 previously infected individuals. They focused on a single mutation located in the part of the Spike protein that attaches to the surface of human cells (as opposed to the part that opens the cell membrane).
All but one of the 14 serum samples were able to block the infection with the virus designed without Spike mutations. But all the serums were less effective in blocking infections by viruses that carried a single-mutated Spike protein found in mink. However, they could all block the virus; it took more serum to do this.
Looking more closely at this, the researchers tested the two antibodies used in a potential COVID-19 therapy by Regeneron. Any of these antibodies are able to block the infection of human cells cultured by SARS-CoV-2 on their own. But when he was 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 that changes Spike’s profile from an immune system perspective.
What this means?
The specific mutation that alters the immune response has also been observed in strains that have adapted to circulate in ferrets and are in a location that physically interacts with a human protein. So, in all likelihood, this mutation was selected to allow for a more effective mink infection. In contrast, the mutation was rarely seen in humans – only one report was found in a person with a persistent infection.
The same virus seems to infect human cells a little less well. This suggests that current adaptations to mink do not appear to make the virus more dangerous to humans in this regard, although we cannot rule out that further evolution will not have different implications for humans.
Potentially more worrying is the reduced immune profile of the virus. We have designed antibodies that block the virus for use as therapies and we use them as a measure of an effective immune response. So the changes there are striking.
That being said, the ability of antibodies to block Spike is reduced, not eliminated. And we are still not sure about the relative importance of antibody neutralization to other aspects of the immune response. So, although it sounds very bad, it may not have a significant effect on the transmissibility of the virus to humans. Finally, we are probably more exposed to the risk of variants evolving in humans, where they are exposed to the real human immune response.
However, the study reinforces a more general concern about pandemic management. The virus has spread so much that it is no longer a matter of simply controlling it in the human population. We must now also be aware of the risk of the virus spreading to us from one of the domesticated species to which we transferred it.
Cell Reports, 2021. DOI: 10.1016 / j.celrep.2021.109017 (About DOI).