We always had to limit the total SARS-CoV-2 infections for reasons that did not pose the immediate risk to the infected. Every new infected individual is a chance for the virus to develop in a way that makes it more dangerous – more infectious or deadly. This is true even when an individual has a symptom-free infection. The more the virus repeats, the more mutations it will experience and the greater the chance that something threatening will develop.
One of the disturbing discoveries of the past year has been that it is not just the human population that we need to worry about. SARS-CoV-2 has been found in a number of species, especially cats and mink, which we spend a lot of time on. It even spread from there to the wild mink population, and the virus jumped back and forth between people and farmed with mink. These animal reservoirs provide COVID opportunities to develop in ways that make them more dangerous to us – perhaps through mutations that make it possible to adapt to the new species.
A group of German researchers have now tested some of the mutations in viruses that have spread in mink populations, and the news is mixed. One specific mutation makes the virus somewhat less contagious to humans, but reduces the likelihood that antibodies against the virus will recognize it.
A little different
When we first reported on the virus found in mink, we only knew that it picked up mutations while the animals were infected; we were still too early to even compile a list of mutations commonly seen in mink. That has now changed, and the research team has a list to work with; there is now a catalog of mutations that occur in European mink farms but are not distributed in humans. The researchers focused on mutations in the Spike protein, which the virus uses to attach to and infect human cells. Vein is important because it determines which cells can infect the virus, and it is often the target of antibodies that can prevent the virus from entering.
To investigate these mutations, the researchers produced different versions of the Spike protein in a harmless virus and tested whether the engineered virus could infect cells. They found that certain mutations make it harder for Spike to land the virus in some human cells. There were a few more types of human cells that could infect it – especially intestines and lung cells, two major sites of SARS-CoV-2 infection. But the virus infected others more severely.
Separately, the researchers looked at how these mutations fared against the antibody response mounted to SARS-CoV-2 infection using serum obtained from 14 previously infected people. They focused on a single mutation in the part of the Spike protein that adheres 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 infection by the virus produced without any Spike mutations. But all the sera were less effective at blocking infections by viruses containing a Spike protein, altered by a single mutation found in mink. Everyone was still able to block the virus; it just cost more serum to do so.
To investigate this more closely, the researchers examined the two antibodies used in a potential COVID-19 therapy made by Regeneron. Both of these antibodies can block the infection of cultured human cells by SARS-CoV-2 on their own. But when it was tested against Spike who found the mutation in mink, only one of the two antibodies still neutralized it. Again, this is consistent with the mutation that changes Spike’s profile from the perspective of the immune system.
What does it mean?
The specific mutation that alters the immune response has also been seen in strains adapted to circulate in ferrets, and it is at a site that physically interacts with a human protein. Thus, in all likelihood, this mutation was chosen to allow more effective infection of mink. In contrast, the mutation was rarely seen in humans – only one report of it was 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 do not make the virus more dangerous to humans in this regard, although we cannot rule out that further evolution will not have other consequences for humans.
The reduced immune profile of the virus is possibly more worrying. We have designed antibodies that block the virus for use as therapies, and we use it as a measure of an effective immune response. Changes there naturally attract attention.
That said, the ability of antibodies to block Spike is reduced and not eliminated. And we are still not sure about the relative importance of neutralizing antibodies to other aspects of the immune response. Although it sounds really bad, it can not have a significant effect on the transmission of the virus in humans. Ultimately, we are likely to be at greater risk for variants that develop in humans, where they are exposed to the actual human immune response.
Nevertheless, the study reinforces a more general concern about the management of the pandemic. The virus has spread so widely that it is no longer an issue to get it under control only among the human population. We must now also be aware of the risk of the virus spreading to us from one of the domestic animals to which we have transmitted it.
Self-reports, 2021. DOI: 10.1016 / j.celrep.2021.109017 (About DOIs).