Friday, February 16, 2024

Preprint: Emergence & Spread of SARS-CoV-2 Variants from Farmed Mink to Humans and Back - Denmark, June-November 2020.



Credit ECDC

#17,913

After emerging in 2019, SARS-CoV-2 quickly evolved into an overwhelmingly `humanized' virus, but it also found refuge in a large number of non-human hosts, including mink, deer, dogs, cats, and even rodents (see Nature: Comparative Susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV Across Mammals).

This co-circulation in non-human hosts raises concerns we could see new, potentially more dangerous variants of COVID emerge, and spill back into humans at a later date.

While controversial and unproven, in late 2021 a new and highly divergent Omicron virus emerged in South Africa, and there is plausible scientific evidence to suggest it may have first evolved in rodents (see Evidence for a mouse origin of the SARS-CoV-2 Omicron variant).

But even if we discount that event, we know that SARS-CoV-2 spilled over into farmed mink in Denmark in 2020, evolved into a novel strain - which eventually spilled back into humans (see EID Journal: SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark).

Millions of farmed mink were destroyed in order to stop this variant, and for a time Denmark locked down North Jutland, where most of the human cases had been identified, and the UK banned travel to and from Denmark.

Similar outbreaks have been documented in other non-human species, also resulting in a `spill back' into humans, including:




While we've looked at a number of previous accounts of Denmark's mink crisis, today we have a preprint from researchers at Denmark's SSI which sheds new light on both the size and frequency of their spillover events. 

Due to its size (35-pages) I've just posted the Abstract, Author Summary, and conclusion below.  What is striking is how many separate spillover events appear to have occurred (up to 60 Mink-to-human and 136 Human-to-Mink) in Denmark alone

Follow the link to read it in its entirety.  I'll have a postscript after the break. 


Thomas Bruun Rasmussen, Amanda Gammelby Qvesel, Anders Gorm Pedersen, Ann Sofie Olesen, Jannik Fonager, Morten Rasmussen, Raphael Niklaus Sieber,eMarc Stegger, Francisco Fernando Calvo Artavia, Esben Rahbek Thuesen, Marlies Jilles Francine Goedknegt, Louise Lohse, Sten Mortensen, Anders Fomsgaard, Anette Ella Boklund, Anette Bøtner, Graham J Belsham

doi: https://doi.org/10.1101/2024.02.13.580053

          PDF 

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2.

Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. A detailed analysis of the changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here.

The majority of cases in mink involved variants that had the Y435F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early on during the outbreak. However, further introductions of the virus, with variants lacking these changes, from the human population into mink also occurred.

Based on phylogenetic analysis of the available viral genome data, we estimate that there were a minimum of about 17 separate examples of mink to human transmission of the virus in Denmark, using a conservative approach, but up to 60 such events (95% credible interval: (35-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using a Bayesian method. Using the latter approach, it was estimated that there were 136 jumps (95% credible interval: (112-164)) from humans to mink. Thus, transmission of these viruses from humans to mink, mink to mink, from mink to humans and between humans were all observed.

         Author summary

In addition to causing a pandemic in the human population, SARS-CoV-2 also infected farmed mink. In Denmark, after the first identification of infection in mink during June 2020, a decision was made in November 2020 to cull all the farmed mink. Within this outbreak, mink on 290 farms (out of about 1100 in the country) were found to have been infected.

We showed, by analysis of the viruses from the mink, that the viruses on the farms were mainly of three different, but closely related, types (termed Clusters 2, 3 and 4) that shared certain distinctive features. Thus, we found that many outbreaks in mink resulted from transmission of the virus between mink farms. However, we identified that new introductions of other virus variants, presumably from infected humans, also occurred. Furthermore, we showed that spread of the virus from infected mink to humans also happened on multiple occasions.  Thus, transmission of these viruses from humans to mink, mink to mink, from mink to  humans and between humans were all observed.  

          (SNIP)

Concluding remarks 

It is apparent that SARS-CoV-2 readily infected farmed mink and spread quickly between farms. Transmission from infected humans to mink and from infected mink to humans occurred on multiple occasions and the mink-derived viruses then spread among  people. There were legitimate concerns that replication of SARS-CoV-2 in a large population  of mink could generate novel variants that would have adverse effects on human health due  to antigenic change, greater transmissibility or higher fitness.

However, mink-derived viruses with such unwelcome characteristics did not spread among humans before the mink population was culled. Variants of SARS-CoV-2 that did arise in mink (e.g. with the changes Y453F and H69/V70del in the S protein) were transmitted to, and within, the human  population but died out either before, or soon after, the culling of the mink population in DK. 

          (Continue . . . )


This spillover from mink-to-humans occurred at roughly the same time that a new and improved Alpha variant was starting to spread in the UK and Europe, one which quickly overwhelmed these escaped mink variants.  

Had that not happened, the trajectory of the COVID pandemic going into 2021 might well have been different. 

Since then we've seen repeated reports of spillovers of SARS-CoV-2 (and avian influenza) into mink farms, and while reports of subsequent spill back into humans have been rare, it isn't clear how closely some countries are looking. 

Last summer, in PNAS: Mink Farming Poses Risks for Future Viral Pandemics, we looked at an excellent opinion piece penned by two well known virologists from the UK (Professor Wendy Barclay & Tom Peacock) on why fur farms - and mink farms in particular - are high risk venues for flu.

While our current COVID emergency has been declared over, the virus has not gone away, and a new zoonotic spillover of a mutated variant could present the world with an enormous setback. 

Hence the warning contained in the WHO/FAO/OIE Joint Statement On Monitoring SARS-CoV-2 In Wildlife & Preventing Formation of Reservoirs.