With no end to the coronavirus disease 2019 (COVID-19) pandemic in sight, potential new reservoirs of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in animal populations are closely watched. A new study published in the journal Science in November 2020 describes the probable transmission of the virus between farmed minks and humans working on the mink farm, even with biosecurity measures in place and the culling of infected farms as soon as an infection is reported.
Zoonotic virus infects many animal species
The COVID-19 pandemic has been strongly suspected to be zoonotic from the start when the Wuhan sea fish and wild animal meat market was thought to be the source. However, many cases were later traced back to before the earliest market-linked case, suggesting other sources could be possible. In short, the intermediate animal host of SARS-CoV-2 is yet to be identified.
The virus in question has been shown to successfully infect dogs, cats, ferrets, hamsters, and many non-human primates, but not pigs and several kinds of poultry. The natural infection has been detected in some pet dogs and cats and zoo-kept tigers and lions. More recently, cases have also been reported in large numbers in farmed mink.
Separate infections on each farm
The current study used whole-genome sequencing to analyze the patterns of infection on mink farms in the Netherlands, using genetic sequencing data along with epidemiological and surveillance data. Early on, only two Dutch mink farms were implicated in April 2020. This was followed by an examination of all the mink farms in the country to identify the routes of transmission.
The study focuses on the results from the first 16 farms where mink were found to be infected. This included around 100 people, half had a positive RT-PCR test, and half had a positive serological test. About 70% of the people tested were positive overall.
From the first two farms found to be infected, one had no cases, and one had a single hospitalized employee before the first interview, but all the employees on the second farm had antibodies to the virus. The viral sequences obtained from the two farms were distinct, showing that each farm had been infected separately.
Sequence clusters in same-farm humans and minks
With the next farm, the employees first tested negative for the virus but later developed symptoms. Several then tested positive. In all these farms, the same sequences were obtained from infected humans and mink at each farm.
There were five different clusters from 16 mink farms, but the clusters did not appear to follow any geographic pattern, even though many farms within a cluster had the same owner. Of the 18 sequences from the mink farmworkers or their close contacts, from 7 farms, the human and mink sequences were almost identical. However, in two farms, the human and mink sequences were different. In two farms, the mink sequences from one clustered with the human sequences from another because of the staff's movement between the two farms.
The sequence clusters found on these farms differed from those found in COVID-19 cases in the neighboring area. This rules out community-acquired infection. The infection also did not appear to have come from Poland, a possibility with the Polish origin of many seasonal migrants.
Rapid viral evolution
A peculiarity of the mink infections was the rapid evolution of the virus in these animals, with up to 12 single nucleotide polymorphisms and deletions of up to 9 nucleotides being observed within one farm's sequences. None of these mutations were unique, being found in humans as well.
Almost 70% of the farmworkers and their close contacts were infected, which shows that the presence of mink infection is a risk factor for COVID-19. Again, C>U substitutions for U>C substitutions were noted recently to be eight times higher. Such substitutions are a marker of host adaptation. This marker was present, though at a lower level, and 3.5 times higher in mink sequences.
The estimated annual substitution rate per site is around 1.16*10^-3 for this virus, or around a mutation a week. This accounts for the high diversity in sequences and suggests the virus had been circulating in mink farms for weeks prior to detecting the first case.
The mutation rate seems to be relatively rapid since even when the PCR came up negative one week before the first positive case, the sequences isolated from that farm continued to show relative diversity. One reason could be the high mink density, which favors viral spread and exposure to high doses of the virus.
Implications for public health
The outbreak on these farms appears to have originated in animals since the human and animal sequences from the farms show phylogenetic separation from the community-derived sequences. However, these infections did not appear to cause community outbreaks.
The study could not identify how the infection spread from farm to farm, but the authors suggest that temporary workers, who were not tested, might have been involved. They caution, "SARS-CoV-2 infections have also been described in mink farms elsewhere. It is imperative that fur production and the trading sector should not become a reservoir for future spillover of SARS-CoV-2 to humans."
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