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Cluster 5 (SARS-CoV-2)

Cluster 5 (SARS-CoV-2)

Cluster 5 refers to a cluster of SARS-CoV-2 viral infections characterized by altered spike proteins which likely result from a mutation of the virus in farmed mink populations in Denmark.

Cluster 5 refers to a cluster of SARS-CoV-2 viral infections characterized by altered spike proteins which likely result from a mutation of the virus in farmed mink populations in Denmark. The variant emerged in mid-2020, and in November 2020, the Danish government ordered a cull of the country's roughly 17 million farmed mink to reduce spread of SARS-CoV-2.

Background

SARS-CoV-2 is the virus which causes COVID-19. Its origin is likely zoonotic, “spilling over” from animals to humans.

Zoonotic origins of the virus

The precise zoonotic path to humans is unknown but the virus is suspected to have passed through mammalian reservoirs including bats or pangolins, or a combination thereof, before infecting humans in or near Wuhan, China, in the latter half of 2019.

Coronavirus and ACE2

In infected hosts, SARS-CoV-2 spike proteins bind to the angiotensin-converting enzyme 2 (ACE2) receptor.

Minks as a SARS-CoV-2 reservoir

In July 2020, Hayashi et al published a preprint of a study establishing the structural homology (or similarity) between ACE2 receptors in humans and minks, resulting in minks’ susceptibility to the virus. Their research was performed pursuant to reports, in April and May, of COVID-19 outbreaks at mink farms throughout the Netherlands and Denmark. A preprint of a study by Munnick et al from September 2020 found that farmed minks likely contracted the virus from infected humans working on those farms. Their study also documents instances and mechanisms of SARS-CoV-2 jumping back from minks to human farm workers.

Cluster 5 mutation

Mutations can occur as part of the viral replication process. On November 5, 2020, health officials at Denmark's State Serum Institute ("Statens Serum Institut" in Danish) said they have identified 216 farms at which mink have been infected with SARS-CoV-2. Mink variants of SARS-CoV-2 have been found in 214 people living in the Danish region of North Jutland, the world’s largest mink-producing region. 535 samples in total have been sequenced from North Jutland, meaning that ~40% of the region’s samples were mink variants found in humans.

Spike protein mutation

The Danish outbreak is occurring in five (5) clusters. The fifth cluster (“Cluster 5”) is characterized by a mutated SARS-CoV-2 virus with changes to four amino acids in the genetic code for its spike proteins: H69del / V70del, Y453F, I692V and M1229I, according to SSI. The Cluster 5 virus has been found in samples from 5 mink farms and 12 samples from human patients.

Spread of Cluster 5 variant

According to Danish health officials, 4 of the infected people were directly connected to mink farms, indicating the possibility of community spread to the other 8 human patients. A November 6th update from SSI states that 11 of the human cases of Cluster 5 SARS-CoV-2 occurred in North Jutland. One case was initially reported in the region of Zealandbut SSI department head Tyra Grove Krause later stated that the Zealand case was a reporting error and that all 12 cases are located in North Jutland.

Potential risk

Denmark’s State Serum Institute found that the mink variant of SARS-CoV-2 from Cluster 5 exhibited decreased susceptibility to antibodies for the predominant strains of SARS-CoV-2 circulating in humans. The SSI sent a new risk assessment to the Danish Ministry of Health on November 3, 2020. The assessment states that continuation of mink farming operations in North Jutland would entail significant risk to public health and that the Cluster 5 variant could pose a threat to current SARS-CoV-2 vaccine development efforts if community spread occurs. Immunity conferred by a SARS-CoV-2 vaccine based on the widely circulating virus in humans may not protect against the Cluster 5 variant, SSI suggested.

Response
Danish mitigation measures

A statement released by the World Health Organization (WHO) on November 6th detailed the public health actions taken in response to the Cluster 5 variant:

  • Culling of all farmed mink (over 17 million animals) in Denmark, including the breeding stock
  • Enhancing surveillance of the local population to detect all COVID-19 cases, including through population-wide mass PCR testing for the region of North Jutland;
  • Expanding the percentage of sequencing of human and mink SARS-CoV-2 infections in Denmark;
  • Rapid sharing of the full genome sequences of the mink-variant SARS-CoV-2; and
  • Introducing new movement restrictions and other public health measures to affected areas in North Jutland to reduce further transmission, including movement restrictions between municipalities.
U.K. response

On November 6, 2020 the United Kingdom announced that it would remove Denmark from its whitelist of countries from which travelers can arrive without needing to self-isolate for 14 days.

On November 8, Jonathan Van Tam—Britain's Deputy Chief Medical Officer—announced an order for all U.K. hospitals to isolate SARS-CoV-2 patients who carry mink variants, including the Cluster 5 mutation, of the virus.

Other mink SARS-CoV-2 outbreaks

So far, the Cluster 5 spike protein variant is circulating only in Denmark, as of Friday November 6th. However, mink farming operations outside of Denmark have also been affected by SARS-CoV-2:

  • The Netherlands has ordered a cull of hundreds of thousands of mink since June 2020.
  • In October 2020, nearly 10,000 animals died in mink farms across the U.S. state of Utah.

Timeline

November 6, 2020
World Health Organization (WHO) releases statement on the mink-associated SARS-CoV-2 strain

The WHO's statement covers information released by the State Serum Institute in Denmark and asserts that "Further scientific and laboratory-based studies are required to verify preliminary findings reported and to understand any potential implications of this finding in terms of diagnostics, therapeutics and vaccines in development. In the meantime, actions are being taken by Danish authorities to limit the further spread of this variant of the virus among mink and human populations."

November 4, 2020
Prime Minister Mette Frederiksen announces full cull of Denmark's farmed mink population

Frederiksen made the announcement in a press conference and an accompanying Facebook post stating that the mutation of SARS-CoV-2 spike proteins found in Cluster 5 may pose a risk to the efficacy of vaccines currently in development to prevent COVID-19. Frederiksen acknowledged that the order to cull the nation's farmed mink population may threaten the continuation of multi-generational family businesses in the mink fur industry.

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