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With an end to the 2019 coronavirus disease (COVID-19) pandemic in sight, the potential new reservoirs of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in animal populations are closely monitored. A new study published in the journal Science in November 2020 describes the probable transmission of the virus between farmed mink and humans working on the mink farm, even with biosecurity measures in place and the culling of infected herds as soon as an infection is reported.
The zoonotic virus infects many animal species
The COVID-19 pandemic was heavily suspected of being zoonotic from the start, when the source was thought to be Wuhan’s seafood and bushmeat market. However, many cases have subsequently been traced back to before the first market-related case, suggesting that other sources may be possible. In short, the SARS-CoV-2 intermediate animal host has yet to be identified.
It has been shown that the virus in question successfully infects dogs, cats, ferrets, hamsters and many non-human primates, but not pigs and various types of poultry. Natural infection has been detected in some pet dogs and cats, tigers and lions raised in the zoo. More recently, numerous cases have also been reported in farmed mink.
Separate infections on each farm
The current study used whole genome sequencing to analyze infection patterns in mink farms in the Netherlands, using genetic sequencing data along with epidemiological and surveillance data. Initially, only two Dutch mink farms were involved in April 2020. This was followed by an examination of all mink farms in the country to identify routes of transmission.
The study focuses on the results of the first 16 farms where the minks were found to be infected. This included approximately 100 people, half had a positive RT-PCR test and half had a positive serological test. About 70% of the people tested tested positive overall.
Of the first two farms found infected, one had no cases and one had only one employee hospitalized prior to the first interview, but all 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 groups in humans and mink from the same farm
With the next farm, the employees first tested negative for the virus, but later developed symptoms. Several then tested positive. In all of these farms, the same sequences were obtained from infected humans and minks on each farm.
There were five different clusters from 16 mink farms, but the clusters did not appear to follow any geographical pattern, even though many farms within a cluster had the same owner. Of the 18 sequences of mink breeders or their close contacts, from 7 herds, the sequences of men and mink were nearly identical. However, in two farms, the human and mink sequences were different. In two farms, the mink sequences of one were clustered with the human sequences of another due to the movement of staff between the two farms.
The sequence clusters found on these farms differed from those found in COVID-19 cases in the neighboring area. This excludes community-acquired infection. Furthermore, the infection did not appear to come from Poland, a possibility with the Polish origin of many seasonal migrants.
Rapid viral evolution
A particularity of 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 observed within a farm’s sequences. None of these mutations were unique, having also been found in humans.
Nearly 70% of agricultural workers and their close contacts have been infected, which shows that the presence of mink infection is a risk factor for COVID-19. Again, the C> U substitutions for the U> C substitutions have recently been noted as being eight times higher. Such substitutions are an indicator of host adaptation. This marker was present, albeit at a lower level, and 3.5 times higher in the mink sequences.
The estimated annual replacement rate per site is approximately 1.16 * 10 ^ -3 for this virus, or approximately one mutation per week. This explains the high diversity in the sequences and suggests that the virus had been circulating in mink farms for weeks before detecting the first case.
The mutation rate appears to be relatively rapid since even when the PCR was negative a week before the first positive case, the sequences isolated from that herd continued to show relative diversity. One reason could be the high mink density, which promotes viral spread and high dose exposure of the virus.
Public health implications
The outbreak in these herds appears to have originated in animals as human and animal sequences from herds show phylogenetic separation from community-derived sequences. However, these infections did not appear to cause outbreaks in the community.
The study was unable to identify how the infection spreads from one farm to another, but the authors suggest that temporary workers, who have not been tested, may have been involved. They warn that “SARS-CoV-2 infections have also been described in mink farms elsewhere. It is imperative that fur production and the commercial sector do not become a reservoir for the future spread of SARS-CoV-2 to humans. “.
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