Mink farms pose extreme risk of spreading SARS-CoV-2, and a new study explains why.

We now have an even more detailed explanation for the unique susceptibility of farmed mink to SARS-CoV-2 – after COVID-19 outbreaks ricocheted through approximately 440 mink factory farms in Europe and in the U.S., along with three variants spawned.

A recently published scientific paper out of the University of Cambridge School of Veterinary Medicine suggests that the worldwide factory farming of wild mammalian carnivores — such as mink, raccoon dogs, foxes and civet cats for fur or food — poses acute public health risks. This is because the Carnivore Order of mammals have deficiencies in their innate immune systems that permit them to become infected and then carry (rather than kill) zoonotic viruses, bacteria, and parasites. These parasites and pathogens can then be transmitted to other susceptible animals and people.

The bottom line: Keeping large numbers of farmed carnivores crowded together on “farms” creates perfect conditions for the pathogens to be carried, to amplify their numbers and, perhaps most importantly, to mutate, according to the authors.

This basic biological fact may help to explain why civet cats farmed in southern China for food and sold in hundreds of “live markets” in southeast Asia were the source and reservoir of the SARS-1 virus in the 2002-2004 epidemic that infected 8,000 people and killed at least 774. This phenomenon may also explain why factory farmed mink in Europe and North America have been heavily infected by SARS-CoV-2 and. in turn. infected thousands of people worldwide. Farmed mink in China are also suspected to be the intermediate “missing link” between bats and people that spawned the COVID-19 pandemic, according to the World Health Organization.

This is an especially significant paper — among a cascade of reports about a COVID-19 pandemic among mink that has paralleled the outbreak in humans. Its findings make it even more urgent for lawmakers to act on a mink farming ban proposed in Congress (H.R. 4310) by Reps. Rosa DeLauro, D-Conn., and Nancy Mace, R-S.C.).  A complete fur-farming ban has been proposed for the European Union by Austria and the Netherlands, and broadly supported by other nations, including fur-farming giant Poland.

The researchers noted that approximately 49% of all carnivores (e.g. mink, cats, dogs, bears, civet cats) carry one or more unique zoonotic pathogen, the highest proportion of any mammalian order. The hypothesis they investigated was whether high presence of zoonotic pathogens in Carnivores was simply because Carnivores form such a large group of animals (at least 270 species), or because of differences in their immune systems (vs non-carnivore mammals) that favored pathogen carriage. The investigators uncovered surprisingly strong experimental evidence of the latter. Specifically, the researchers discovered that Carnivores have a severely muted and compromised inflammatory response to infections by all pathogens.

The researchers used a combination of (1) comparative genomics of the immune system i.e. they closely examined the DNA sequences of immune system genes from many mammals; and (2) in vitro cell culture experiments to investigate the inflammatory response to pathogens of carnivores and non-carnivores. Their studies focused on the so-called “inflammasome” — a complex and vital part of the mammalian immune response that aims to both detect and wipe out pathogen or parasite cell invaders.

When the body becomes injured, biochemical responses are activated (e.g. blood clotting and inflammation). The inflammasome mediates an intra-cellular inflammatory response to injury or illness, mostly in white blood cells called macrophages. In response to microbial infection, the inflammasome is activated and contributes to host protection by inducing immune responses that limit microbial invasion, ideally and typically ending in the death of the pathogen invader.

The inflammasome is made up of a suite of proteins governed by chemicals called receptorsadapters, and effectors in white blood cells called macrophages. Receptors “sound the alarm” when an invader is detected and cause adapters (chemical messengers) to release effectors, which are powerful enzymes that destroy the invaders e.g. by lysing (killing) infected host cells by punching holes in their cell membranes (like popping a balloon).

From (1) comparative genomics, the investigators found that carnivores have several missing or disabled inflammasome receptor genes, permitting pathogens to go unseen or be poorly detected, to fly under the radar, so to speak. Carnivores also have dysfunctional fused effector genes that compromise the immune response to pathogen invaders. In (2) a series of cell culture experiments in a model system of macrophages from dogs (representative carnivore) and mice (representative non-carnivore) infected with Salmonella (a representative common bacterial pathogen that invades macrophages), the researchers found profound compromised inflammasome functionality, including failure of dog macrophages to kill Salmonella infected macrophages. As expected and unlike in dogs, infected mice macrophages were quickly lysed. When dog inflammasome genes were inserted in mice macrophages, the genetically modified mice macrophages also failed to kill the Salmonella-infected cells.

[In summary, the inflammasome that should start with detecting pathogens and end in killing them inside infected cells is either genetically or functionally missing from Carnivores. To compensate for their compromised inflammasome, it is believed that the high-protein diet consumed by carnivores has protective antimicrobial properties. However, outside of the gut, the dysfunctional Carnivore inflammasome is apparently very detrimental.]

According to Dr. Clare Bryant who led the study, pet carnivores like dogs and cats are unlikely to pose much risk zoonotic risk. However, the real danger comes when carnivores (e.g. mink, civet cats) are crowded together in close quarters on factory food or fur farms, giving pathogens a large pool and time (since they are carried but not killed) in which to mutate and thus adapt to infect new hosts such as people. Thus, factory-farmed Carnivores can serve as either originators or amplifiers of zoonotic infections. The emergence in 2020 of at least three mink-origin SARS-CoV-2 strains with enhanced human virulence supports Dr. Bryant’s hypothesis in the real world. Thus, molecular biology and animal welfare fields agree: wildlife farming of carnivores for food or fur is especially dangerous.

Jim Keen, D.V.M., Ph.D., director of veterinary science for the Center for a Humane Economy, is a former infectious disease scientist at the U.S. Department of Agriculture and a former faculty members at the University of Nebraska College of Veterinary Medicine and Biomedical Sciences.

Note: Digby Z, Tourlomousis P, Rooney J et al, 2021. Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections. Cell Reports. 36, 109614 August 24, 2021