Thursday, November 19, 2020

EID Journal: SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark

Credit ECDC


As early as May of this year (see COVID-19: Back To The Mink Farm) it was apparent that farmed mink were particularly susceptible to SARS-CoV-2 infection and that there were hints of mink-to-human transmission.   

The susceptibility of mink to COVID wasn't that much of a surprise given they are closely related to ferrets - which are often used in influenza research - and their long history of hosting both human and novel flu strains.  

A few (of many) past studies include:

Nature: Semiaquatic Mammals As Intermediate Hosts For Avian Influenza 

Vet. MicroB.: Eurasian Avian-Like Swine Influenza A (H1N1) Virus from Mink in China
H9N2 Adaptation In Minks 

While laboratory experiments showing that swine, poultry, and other farmed animals are relatively poor hosts for COVID were reassuring, its proclivity for infecting mink - and to a lesser extent dogs and cats - has been problematic. 

Viruses, when they jump species, often evolve to adapt to their new hosts. SARS-CoV-2 has undoubtedly being doing that in humans (see Another SARS-CoV-2 D614G Mutation Study), and there are few reasons not to believe it would happen in mink (or any other intermediate host).

Just over two weeks ago Denmark announced the discovery of a mutated SARS-CoV-2 virus in both Mink and in humans, prompting authorities to order the depopulation of 17 million mink (see Denmark Orders Culling Of All Mink Following Discovery Of Mutated Coronavirus).

While the full public health impact of this new COVID strain has yet to be established, there were immediate concerns that it might be more resistant to the vaccines currently being developed. 
In response, Denmark temporarily locked down North Jutland where most of the human cases had been identified, and the UK quickly banned travel to and from Denmark.

Over the past two weeks we've seen risk analyses issued from Denmark, the ECDC, and the World Health Organization.  While citing theoretical risks, all called for more information on the event.  

More recently, Denmark's Statens Serum institute issued a more reassuring statement indicating that they have not detected the problematic `5th cluster strain' in humans since mid-September, and may have contained (or eradicated) the threat.

Contained or not, the fact that a worrisome mutation emerged from farmed mink in Denmark raises concerns that the same (or other) mutations might emerge from mink farms elsewhere in the world. 

All of which brings us to an EID Journal Dispatch, from researchers at the University of Copenhagen, Copenhagen, Denmark and the Statens Serum Institut, that describes the recent zoonotic spread of a mutated COVID-19 virus from mink to humans in Denmark.

While it doesn't answer the $64 question of how much of an impact this `5th Cluster Strain' might have on the pandemic, it does provide our deepest look to date at the `mechanics of transmission' - and apparent evolution - of SARS-CoV-2 in farmed mink. 

I've only excerpted the abstract, and parts of the conclusion, so follow the link to read it in its entirety. 

Volume 27, Number 2—February 2021


SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark

Anne Sofie Hammer, Michelle Lauge Quaade, Thomas Bruun Rasmussen, Jannik Fonager, Morten Rasmussen, Karin Mundbjerg, Louise Lohse, Bertel Strandbygaard, Charlotte Sværke Jørgensen, Alonzo Alfaro-Núñez, Maiken Worsøe Rosenstierne, Anette Boklund, Tariq Halasa, Anders Fomsgaard, Graham J. Belsham, and Anette Bøtner 


Severe acute respiratory syndrome coronavirus 2 has caused a pandemic in humans. Farmed mink (Neovison vison) are also susceptible. In Denmark, this virus has spread rapidly among farmed mink, resulting in some respiratory disease. Full-length virus genome sequencing revealed novel virus variants in mink. These variants subsequently appeared within the local human community.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the ongoing coronavirus disease (COVID-19) pandemic (1). Ferrets, cats, dogs, Syrian hamsters, and nonhuman primates can be infected with the virus and, in some cases, transmit it (2); however, other species, such as pigs and chickens, appear resistant (3,4). Thus, the virus has a restricted host range. Infection with SARS-CoV-2 has occurred in farmed mink in the Netherlands (5).

In Denmark, there are »1,200 mink farms (6). Because of contacts between persons with COVID-19 and mink farms, investigation of SARS-CoV-2 infection within mink in Denmark was undertaken. We documented 3 premises in the Northern Jutland region of Denmark with SARS-CoV-2–infected mink and analyzed virus transmission in mink and the local human community.



A high proportion of mink on farms can be infected with SARS-CoV-2 within a few days, which may provide major virus exposure to persons working with mink. The infections we describe here occurred with little clinical disease or increase in death (Appendix), making it difficult to detect the spread of infection; thus, mink farms could represent a serious, unrecognized animal reservoir for SARS-CoV-2.
There is no evidence for spread of the virus outside of farm buildings, either in Denmark or in the Netherlands (5), except by infected persons. However, there appears to be some risk of virus transmission to persons working with infected mink as well as for their contacts and thus, indirectly, for the public.

On farm 1, the virus had probably been introduced some weeks before detection (Table 1). On farm 2, the low frequency (4%) of seropositivity and the high proportion of qRT-PCR positive animals at second sampling (Table 1) suggested that the virus had been recently introduced but was spreading. Indeed, a third sampling (8 days later) showed a much higher seroprevalence (>90%). Conceivably, the variant viruses that appeared in farm 1 and spread to farms 2 and 3 may be better adapted to mink and thus able to transmit rapidly. The infection at farm 3 was detected relatively late, with a high seroprevalence (66%) at first visit.

A likely scenario for the spread of infection in mink in Denmark is that the index human case-patient, with nt T15656, introduced it into farm 1. Initially, we observed sequence heterogeneity at nt 22920 in mink on farm 1, but subsequently, we detected only the variant form (T22920) on farms 2 and 3 and in subsequent linked human cases (H1–H9) (Table 2).
Remarkably, this heterogeneity also occurred on farm NB02 in the Netherlands. This change, possibly together with the mutation at nt 25936 (Table 2), may represent virus adaptation. It is not yet established whether these changes confer advantages in mink, but the variant viruses in farm 2 spread rapidly.
It seems that the variant viruses on farm 1 spread to >1 human and were then transmitted, presumably by human–human contact, to other persons and to farms 2 and 3. The change at nt 22920 results in substitution Y453F in the S-protein (Table 2). This Y-residue, within the receptor-binding motif of the S-protein, is highly conserved among SARS-related coronaviruses and is close to residue L455 that is critical for interaction with the cellular ACE2 receptor (13).
Dr. Hammer, an associate professor at the University of Copenhagen, is a veterinary pathologist with special interest and expertise in pathological methods applied in diagnostics, research, and surveillance of diseases in fur animals and wildlife. Her research focus has been mainly on viral diseases of carnivorous species.

 While it is possible (although premature to assume) that a crisis has been averted in Denmark, this rapid spread, and adaptation of COVID-19 to mink is a reminder why we focus so much of our attention on `spillover' events in the wild, and on the farm. 

Whether it is H6N1 avian flu turning up in dogs in Taiwan, or an avian H10N7 decimating hundreds of gray seals in Northern Europe, or a rodent-borne pox virus jumping to humans in central Africa, each spillover event provides new opportunities for a novel virus to adapt to a new host, and potentially spark the next big global health crisis. 

While the odds of any one spillover event escalating into a pandemic are small, there are enough `incidents' each year around the world to make the threat very real.  Which is why, even as we struggle against our current COVID-19 pandemic, we need to be actively preparing for the next `big' threat. 

With apologies to Geoffrey Chaucer; Time and viruses wait for no one.