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SARS-CoV-2 Study Shows Evidence of Animal-to-Human Viral Transmission on Mink Farms

NEW YORK – Researchers in the Netherlands investigating outbreaks of SARS-CoV-2 in humans living or working on 16 mink farms have found that these people were infected with strains of the virus with an animal sequence signature, suggestive of an animal-to-human transmission.

In a study published in Science on Tuesday, the researchers said they conducted an in-depth investigation of the mink farm outbreaks using whole genome sequencing, and found that the virus was initially introduced from humans but has since evolved, most likely reflecting widespread circulation among the mink in the beginning of the infection period several weeks prior to detection.

SARS-CoV-2 had been detected in farmed mink (Neovison vison) in the spring, resulting in signs of respiratory disease and increased mortality. In response to the outbreaks, the Dutch government activated a national response system for zoonotic diseases. While authorities concluded that the public health risk of exposure to animals with SARS-CoV-2 was low, they did acknowledge that there was a need for increased awareness of possible involvement of animals in the COVID-19 pandemic, the researchers wrote. Starting May 20, mink farmers, veterinarians, and laboratories were obliged to report symptoms in mink to the Netherlands Food and Consumer Product Safety Authority, and the government also set up an extensive surveillance system.

Despite the enhanced biosecurity, early warning surveillance systems, and immediate culling of infected animals, transmission occurred between mink farms in three big transmission clusters with unknown modes of transmission, the researchers said.

Overall, 68 percent of the tested mink farm residents, employees, and/or contacts had evidence of SARS-CoV-2 infection, and the whole genome sequences showed that the viral strain infecting these people had an animal sequence signature.

SARS-CoV-2 was first diagnosed on two mink farms in the Netherlands on April 23 and April 25. After the initial detection of the virus on these farms, a wider contact tracing effort was undertaken, eventually encompassing 16 mink farms. In total, 97 individuals were tested by either serological assays and/or RT-PCR, the researchers said. In total, 43 out of 88 upper-respiratory tract samples tested positive for SARS-CoV-2 viral RNA, while 38 out of 75 serum samples tested positive for SARS-CoV-2 antibodies. In total, 66 of 97 of the people tested had evidence of SARS-CoV-2 infection.

On one farm, for example, the researchers obtained a whole-genome sequence for 16 of the mink sampled and one farm employee, and found that the human sequence clustered within the mink sequences, although it displayed seven nucleotides of difference with the closest mink sequence. Virus sequences obtained from animals on a second farm was distinct from that of the first farm, indicating a separate introduction, they said.

On a third mink farm, five of seven individuals working or living on the farm tested positive for SARS-CoV-2 RNA. Whole-genome sequences from these individuals and the clustering of these sequences with the sequences derived from mink at this farm, indicated that the employees were infected with SARS-CoV-2 after mink on the farm became infected.

The sequences generated from the mink farms and their employees were compared with the national database consisting of around 1,775 whole-genome sequences. To discriminate between community-acquired infections and mink farm-related SARS-CoV-2 infections, and to determine the potential risk for people living close to mink farms, WGS was also performed on 34 SARS-CoV-2-positive samples taken from individuals who lived in the same postal code area as the first four mink farms. These local sequences weren't related to the clusters of mink sequences, indicating that there was no spillover to people living in close proximity to mink farms and that the sequences from SARS-CoV-2-infected animals and farm workers were clustered by farm.

Finally, a phylogenetic analysis of the mink SARS-CoV-2 genomes showed that the mink sequences from the 16 farms grouped into five different clusters. In total, the researchers generated 18 sequences from farm employees or close contacts, and determined that the human sequences were nearly identical to the mink sequences from the same farm, in most cases.

"Here we show ongoing SARS-CoV-2 transmission in mink farms and spillover events to humans. More research in minks and other mustelid species is important to understand if these species are at risk of becoming a reservoir of SARS-CoV-2," the authors wrote. "Recently, an 8-fold increase in cytidineto-uridine (C-U) compared to U-C substitutions were described, suggestive of host adaptation. In the mink sequences, we observed a 3.5-fold increase in C-U compared to U-C substitutions but the number of substitutions was limited."

They also noted that they observed a high diversity in the sequences from some mink farms, which is likely explained by multiple generations of viral infections in animals before the increase in mortality was detected.