Monday, June 28, 2021

SSI Study: Denmark's Cluster-5 mink Variant Had Increased Antibody Resistance


A full month before the B.1.1.7 (Alpha) variant was announced by the UK's Health Secretary in  December, and 5 months before the first detection of the B.1.617.2 (Delta) variant in India, Denmark was frantically trying to contain a SARS-CoV-2 variant that had arisen as the virus swept through millions of farmed mink. 

As early as May of 2020 (see COVID-19: Back To The Mink Farm) it was apparent that farmed mink were particularly susceptible to SARS-CoV-2 infection and there were even  hints of possible 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 have a long history of hosting both human and novel flu strains (see Nature: Semiaquatic Mammals As Intermediate Hosts For Avian Influenza). 

In early November of last year,  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).
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.

Actually, there were multiple `mink variant's' (B.1.1.298 lineage), but only one - dubbed `Cluster 5' - appeared to pose any enhanced threat over the `wild type' COVID  (see EID Journal: SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark). 

Although spreading widely in Denmark as late as October, `Cluster 5' proved to be not nearly as transmissible as many of its competitors, and it quickly gave way to more biologically `fit' COVID variants (including, eventually, Alpha).  

While this mink crisis was averted (or, at least traded for a different crisis), SARS-CoV-2 continues to spread through farmed mink - and presumably other animal populations - around the world (see March 2021 CDC: Investigating Possible Mink-To-Human Transmission Of SARS-CoV-2 In The United States), and additional `zoonotic variants' are likely to emerge. 

Just as we've seen humanized flu viruses enter the swine population - mutate over time - and then jump back into humans as a `novel' flu (see Canada: Manitoba Public Health Announces 3rd Swine Variant Case (H3N2v), the the potential for new SARS-CoV-2 variants to emerge from non-human reservoirs is an ongoing concern. 

`Cluster 5' is no longer circulating in humans, but understanding how it evolved - and any increased threat to humans - will be critical in detecting, and containing, any future zoonotic evolution of COVID-19.  

To that end Denmark's SSI (Statens Serum Institut) has published - in Frontiers of Microbiology - their analysis of the Cluster-5 mink Variant.   First, their press release, then a link to the full paper.  I'll have a brief postscript when you return.

The Cluster-5 mink virus variant has now been studied: Decreased sensitivity to antibodies has been confirmed
SSI has investigated the mink variant called cluster-5 (hCoV-19 / Denmark / DCGC-3024/2020, which belonged to the variants under the collective designation B1.1.298). The conclusion is that the worrying findings from the preliminary studies in the autumn of 2020 were correct.
Last edited June 28, 2021
Threat from new virus variants

The unhindered spread of the virus through millions of mink led to accumulations of mutations in i.a. the important nail protein, which is the primary target of protective antibodies. The potential threat from new atypical virus variants necessitated timely investigations of the newly emerged mink variants, such as the cluster-5 variant seen in infected patients.

The need for rapid clarity led to preliminary studies of cluster-5 in the fall of 2020, and the studies showed evidence of resistance to antibodies.

Cluster-5 had 11 amino acid changes, including 5 amino acid changes in spike (Y453F, I692V, M12291I and amino acid elimination 69 + 70) and spread to 19 farms and 14 individuals.
The conclusion is clear: Cluster 5 showed resistance
The new study concludes that the combination of the nail mutations in the cluster-5 virus led to a certain significantly increased degree of antibody resistance in some people after covid-19 infection.

The findings thus confirm the preliminary studies in November 2020.

Following the study of cluster-5 virus, some cluster-5 mink viruses continued to mutate into six amino acid changes in the nail protein. The additional mutated cluster-5 virus variant has not been studied, but shows that the mink variants continued to mutate through infected mink.
Covid among animals should be closely monitored
It is recommended in the article that timely monitoring of zoonotic SARS-CoV-2 infections in animals and especially herds of production animals should be controlled, limited, and closely monitored through sequencing to identify new virus variants of concern or under observation for increased morbidity, increased spread and infectivity as well as increased antibody resistance.

The results have been peer-reviewed and published in the scientific journal Frontiers in Microbiology, June 25, 2021.
Title: "In vitro characterization of fitness and convalescent antibody neutralization of SARS-CoV-2 Cluster-5 variant emerging in mink at Danish farms" .

Ria Lassaunière1, Jannik Fonager1, Morten Rasmussen1, Anders Frische1, Charlotta Polacek1, Thomas Bruun Rasmussen1, Louise Lohse1, Graham J. Belsham2, Alexander Underwood3,4, Anni Assing Winckelmann3,4, Signe Bollerup4, Jens Bukh3,4, Nina Weis4,5, Susanne Gjørup Sækmose6, Bitten Aagaard7, Alonzo Alfaro-Núñez1, Kåre Mølbak2,8, Anette Bøtner1,2 and Anders Fomsgaard1*

Mink aren't the only possible non-human reservoir for SARS-CoV-2, and while farmed animals pose the highest risk - due mostly to high livestock densities and greater opportunities for human contact - it is also possible that the virus could establish itself in the wild (see EID Journal: SARS-CoV-2 Exposure in Escaped Mink, Utah, USA).

It is worth noting that while MERS-CoV has never evolved to transmit well enough in humans to sustain a major epidemic, it remains a perennial threat because it is endemic in camels (where it  continues to evolve), and occasionally jumps to humans.   

Companion animals, primarily dogs and cats, are also also susceptible to infection.  The CDC maintains a website on what we currently know about SARS-CoV-2 in non-human hosts. 
COVID-19 and Animals 
updated June 4, 2021 

What you need to know

We do not know the exact source of the current outbreak of coronavirus disease 2019 (COVID-19), but we know that it originally came from an animal, likely a bat.

At this time, there is no evidence that animals play a significant role in spreading SARS-CoV-2, the virus that causes COVID-19, to people.

Based on the available information to date, the risk of animals spreading COVID-19 to people is considered to be low.

More studies are needed to understand if and how different animals could be affected by COVID-19. We are still learning about this virus, but we know that it can spread from people to animals in some situations, especially during close contact.

People with suspected or confirmed COVID-19 should avoid contact with animals, including pets, livestock, and wildlife.

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