The mink link: How Covid-19 mutations in animals affect human health and vaccine effectiveness

The importance of commercially raised animals in the Covid-19 pandemic has received much attention in the past few weeks, when a new variant of SARS-CoV-2 was detected in farmed mink. Unfortunately, mink tend to be relatively susceptible to respiratory infections, and these can readily spread through mink farms due to high-density housing.

Data from from the Netherlands earlier in the pandemic have revealed that mink can be readily infected with SARS-CoV-2 and then pass the virus to humans. In Denmark, 214 people people have been infected by a variant of SARS-CoV-2 that is presumed to have mutated in Danish mink. Over 200 mink farms had tested positive for SARS-CoV-2, and at least five different mink variants of the virus have been detected so far.

These events initiated a mass culling of farmed mink in that country (although this was limited due to legal issues), and cast a spotlight on the disturbing scenario of human-to-mink-to-human transmission of SARS-CoV-2, with potential for the virus to change in mink prior to re-infecting people.

Specifically, this latest occurrence unveils the possibility that mink can serve as an alternate host to promote mutations of SARS-CoV-2, which can be passed back to humans and other animals, both domestic and wild and potentially placing the wild mustelid (minks, ferrets and related species) population at risk.

We are researchers in the fields of virology, immunology and pathology. Our research programs bridge human and animal health and study the transmission of viruses, immune responses to viruses, how viruses cause diseases, and developing strategies such as vaccines to prevent infectious diseases. The recent news linking mink to the current pandemic highlights the importance of research at the interface of animal and human health.

Since the start of the Covid-19 pandemic, the world has learned much about virology, as well as the concept of One Health. At the core of One Health is the idea that human and animal health are intertwined in a shared environment, and that we need to broaden our perspectives beyond human health alone.

Indeed, animals have been at the centre of this pandemic from the beginning. Overwhelming evidence suggests that this coronavirus (SARS-CoV-2), which causes Covid-19, originated from bats. There is debate about whether an intermediate animal host might have harboured additional changes to SARS-CoV-2 to produce the current virus that spreads efficiently person to person. The leading candidate for this is a scaly anteater known as a pangolin.

What is known for sure is that changes to coronaviruses can occur over time due to inherent and purposeful errors in these viruses' ability to copy their genetic codes. This allows a virus to make small changes over time and is an efficient way for them to adapt to new environments.

One of the recently identified Danish mink strains is particularly concerning because changes in the genome occurred in what is called the virus's spike protein, which it uses to enter human cells. These changes have been detected in 12 human cases related to this particular mink variant. Fortunately, this change does not seem to correlate with worse clinical outcomes, based on a small number of cases.

The spike protein is also the primary target of natural and vaccine-induced immune responses to the virus. In theory, if SARS-CoV-2 mutates too much, the immunity derived from the parental virus, acquired either by natural infection or vaccination, could become less effective against the new strain.

The good news is that, so far, there's no evidence that the mink-derived SARS-CoV-2 mutant can bypass natural or vaccine-induced immunity. Fortunately, our immune systems are designed to generate antibodies against multiple parts of the spike protein. This means that if only a small part of the spike protein is mutated, antibodies against other parts of the protein should still confer at least some protection.

The fact that SARS-CoV-2 can change highlights the need for vaccines that not only induce protective antibodies but that can also elicit robust T cell responses, which is the other major mechanism by which our immune systems can kill viruses. Like antibodies, T cells will target multiple parts of viral proteins, thereby increasing the chance of maintaining immunity against non-mutated regions of the proteins.

It might also be important to consider making vaccines that target more than one of the proteins from SARS-CoV-2. It's very difficult for a virus to make major changes to multiple proteins without compromising its fitness.

The other issue that the mink SARS-CoV-2 brings to the forefront of the vaccine development effort is the need for vaccines that are "plug-and-play." These are vaccine technologies where the viral protein the vaccine is designed to target can be readily swapped with a different version of the viral protein.

Once approved by health regulators as being safe and efficacious against a highly pathogenic coronavirus, such technologies could, in theory, be rapidly modified to target emerging mutant viruses; akin to the annual flu vaccine that gets modified every year to target emerging influenza virus variants.

With mink being confirmed only recently as a possible reservoir for SARS-CoV-2, more research is urgently needed to inform rationally based decisions to cull millions of these animals. Even if mass cullings continue, it is unlikely that mink farms will be completely phased out at the global level in the near future. So the question becomes how do we manage the potential threat to human health of SARS-CoV-2 in mink over the long term?

First, enhanced biosecurity measures should be implemented on mink farms.

Second, screening of farmed mink for coronaviruses should be added to the surveillance programs of animal health regulatory agencies, with this information made available to human health regulators.

Third, consideration could be given to tailoring Covid-19 vaccines for animal reservoirs, which would now include farmed mink. These recommendations would not only reduce the potential spread of coronaviruses from mink to humans, it would simultaneously address SARS-CoV-2-related health issues for mink. Indeed, mink can develop Covid-19 after becoming infected with SARS-CoV-2 and it can sometimes be severe and lethal, with no effective current treatment.

Unless future evidence suggests otherwise, it may be best to stay the course with current vaccine development programs with the goal of getting multiple technological platforms approved for use in humans. Then these platforms can be readily modified, akin to the annual influenza vaccine, to target emerging mutant viruses, if warranted.

Simultaneously, public health agencies with any interest in promoting human health should expand their visions to include the health and surveillance of domestic animals and wildlife at the point where human and veterinary medicine interface.

In the case of SARS-CoV-2, humans are currently the largest reservoir of the virus on Earth, and the threat of spillover from human hosts to farmed animals and wildlife species is now made evident. This is an opportune time to take stock in our relationships with animals and the natural world and take action to ensure health for all and this biosphere we share.