TRACKING TWO-WAY HUMAN-MINK TRANSMISSION DURING AN OUTBREAK OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 ON A FARM IN BULGARIA

Authors

  • Ivelina Tifonova National Centre of Infectious and Parasitic Diseases Author
  • Lyudmila Lazarova National Diagnostic and Research Veterinary Medical Institute, Sofia, Bulgaria Author
  • Simona Tchakarova National Diagnostic and Research Veterinary Medical Institute, Sofia, Bulgaria Author
  • Dean Donchev National Centre of Infectious and Parasitic Diseases Author
  • Ivan Stoikov National Centre of Infectious and Parasitic Diseases Author
  • Lyubomira Grigorova National Centre of Infectious and Parasitic Diseases Author
  • Ivan Ivanov National Centre of Infectious and Parasitic Diseases Author
  • Ivailo Alexiev National Centre of Infectious and Parasitic Diseases Author
  • Neli Korsun National Centre of Infectious and Parasitic Diseases Author
  • Iva Christova National Centre of Infectious and Parasitic Diseases Author

DOI:

https://doi.org/10.58395/10vta464

Keywords:

SARS-CoV-2, mink, whole genome sequencing, Oxford Nanopore technology, two-way transmissions

Abstract

Introduction: During the COVID-19 pandemic, it was observed that SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) can be transmitted from humans to various animals. Our study aims to examine the genetic evidence for transmission of SARS-CoV-2 from humans to mink and potentially back to humans in the first reported outbreak on a mink farm in Bulgaria.

Materials and methods: Between October 2 and 29, 2023, 420 oropharyngeal samples from minks on a farm in Central Bulgaria were examined for SARS-CoV-2. Positive samples with Ct <32 were sequenced using Oxford Nanopore technologies.

Results: On 18 October 2023, 98 of 118 mink samples tested positive for SARS-CoV-2. In addition, on 25 October, a mink caretaker from the same farm was confirmed to be infected with SARS-CoV-2. Phylogenetic analysis of the isolated SARS-CoV-2 revealed that the mink caretaker and two minks had a variant similar to FY.1.2 (37.5%), while five other minks were infected with a different variant similar to XBB.1.22 (62.5%). This suggests the presence of another source of infection on the farm with the XBB.1.22 variant. Furthermore, we identified a substitution at position I478K in the receptor-binding motif (RBM) of the receptor-binding domain (RBD) of S-protein in 2 mink samples.

Conclusion: Based on the epidemiological and genetic analysis, our findings suggest a potential for human-to-mink and mink-to-human transmission of SARS-CoV-2. Tracing the route of transmission from an animal host to humans will help elucidate the route of origin and causality for the accumulation of mutations leading to the emergence of new human coronaviruses (HCoVs) and their variants with stronger or weaker pandemic potential.

Downloads

Download data is not yet available.

Author Biographies

  • Ivelina Tifonova, National Centre of Infectious and Parasitic Diseases

    National Reference Laboratory “Influenza and ARD”

  • Lyudmila Lazarova , National Diagnostic and Research Veterinary Medical Institute, Sofia, Bulgaria

    Department of Exotic and Emerging Diseases

  • Simona Tchakarova, National Diagnostic and Research Veterinary Medical Institute, Sofia, Bulgaria

    Department of Exotic and Emerging Diseases

  • Dean Donchev , National Centre of Infectious and Parasitic Diseases

    Department of Microbiology

  • Ivan Stoikov , National Centre of Infectious and Parasitic Diseases

    Department of Microbiology

  • Lyubomira Grigorova , National Centre of Infectious and Parasitic Diseases

    Department of Virology

  • Ivan Ivanov, National Centre of Infectious and Parasitic Diseases

    Department of Microbiology

  • Ivailo Alexiev , National Centre of Infectious and Parasitic Diseases

    Department of Virology

  • Neli Korsun , National Centre of Infectious and Parasitic Diseases

    Department of Virology

  • Iva Christova , National Centre of Infectious and Parasitic Diseases

    Department of Microbiology

References

1. Kesheh MM, Hosseini P, Soltani S, Zandi M. An overview on the seven pathogenic human coronaviruses. Rev Med Virol. 2022 Mar;32(2):e2282. https://doi.org/10.1002/rmv.2282

2. Zhu Z, Lian X, Su X, Wu W, Marraro GA, Zeng Y. From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir Res. 2020 Aug 27;21(1):224. https://doi.org/10.1186/s12931-020-01479-w

3. Zhou H, Yang J, Zhou C, Chen B, Fang H, Chen S et al. A Review of SARS-CoV2: Compared With SARS-CoV and MERS-CoV. Front Med (Lausanne). 2021 Dec 7;8:628370. https://doi.org/10.3389/fmed.2021.628370

4. Voskarides K. SARS-CoV-2: tracing the origin, tracking the evolution. BMC Med Genomics. 2022 Mar 18;15(1):62. https://doi.org/10.1186/s12920-022-01208-w

5. Banerjee A, Doxey AC, Mossman K, Irving AT. Unraveling the Zoonotic Origin and Transmission of SARS-CoV-2. Trends Ecol Evol. 2021 Mar;36(3):180-184. https://doi.org/10.1016/j.tree.2020.12.002

6. Domańska-Blicharz K, Orłowska A, Smreczak M, Munnink BO, Trębas P, Socha W et al. SARS-CoV-2 Monitoring on Mink Farms in Poland. J Vet Res. 2022 Dec 3;66(4):449-458. https://doi.org/10.2478/jvetres-2022-0066

7. Pramod RK, Nair AV, Tambare PK, Chauhan K, Kumar TV, Rajan RA et al. Reverse zoonosis of coronavirus disease-19: Present status and the control by one health approach. Vet World. 2021 Oct;14(10):2817-2826. https://doi.org/10.14202/vetworld.2021

8. Greenhorn JE, Kotwa JD, Bowman J, Bruce L, Buchanan T, Buck PA et al. SARS-CoV-2 wildlife surveillance in Ontario and Québec. Can Commun Dis Rep. 2022 Jun 9;48(6):243-251. https://doi.org/10.14745/ccdr.v48i06a02

9. Mallapaty S. COVID is spreading in deer. What does that mean for the pandemic? Nature. 2022 Apr;604(7907):612-615. https://doi.org/10.1038/d41586-022-01112-4

10. Oreshkova N, Molenaar RJ, Vreman S, Harders F, Oude Munnink BB, Hakze-van der Honing RW et al. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Euro Surveill. 2020 Jun;25(23):2001005. https://doi.org/10.2807/1560-7917.ES.2020.25.23.2001005

11. Erratum in: Euro Surveill. 2021 Mar;26(12). https://doi.org/10.2807/1560-7917.ES.2021.26.12.210325c

12. Oude Munnink BB, Sikkema RS, Nieuwenhuijse DF, Molenaar RJ, Munger E, Molenkamp R et al. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science. 2021 Jan 8;371(6525):172-177. https://doi.org/10.1126/science.abe5901 Epub 2020 Nov 10.

13. Hammer AS, Quaade ML, Rasmussen TB, Fonager J, Rasmussen M, Mundbjerg K et al. SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark. Emerg Infect Dis. 2021 Feb;27(2):547-551. https://doi.org/10.3201/eid2702.203794

14. Chaintoutis SC, Thomou Z, Mouchtaropoulou E, Tsiolas G, Chassalevris T, Stylianaki I et al. Outbreaks of SARS-CoV-2 in naturally infected mink farms: Impact, transmission dynamics, genetic patterns, and environmental contamination. PLoS Pathog. 2021 Sep 7;17(9):e1009883. https://doi.org/10.1371/journal.ppat.1009883

15. Fenollar F, Mediannikov O, Maurin M, Devaux C, Colson P, Levasseur A et al. SARS-CoV-2, and the Human-Animal Interface. Front Microbiol. 2021 Apr 1;12:663815. https://doi.org/10.3389/fmicb.2021.663815

16. Wasniewski M, Boué F, Richomme C, Simon-Lorière E, Van der Werf S, Donati F, Enouf V et al. Investigations on SARS-CoV-2 and other coronaviruses in mink farms in France at the end of the first year of COVID-19 pandemic. bioRxiv [Preprint]. 2023 Feb 2:2023.02.02.526749. https://doi.org/10.1101/2023.02.02.526749

17. Cossaboom CM, Wendling NM, Lewis NM, Rettler H, Harvey RR, Amman BR et al. One Health Investigation of SARS-CoV-2 in People and Animals on Multiple Mink Farms in Utah. Viruses. 2022 Dec 29;15(1):96. https://doi.org/10.3390/v15010096

18. Sharun K, Tiwari R, Natesan S, Dhama K. SARS-CoV-2 infection in farmed minks, associated zoonotic concerns, and importance of the One Health approach during the ongoing COVID-19 pandemic. Vet Q. 2021 Jan 1;41(1):50-60. https://doi.org/10.1080/01652176.2020.1867776

19. Lu L, Sikkema RS, Velkers FC, Nieuwenhuijse DF, Fischer EAJ, Meijer PA et al. Adaptation, spread and transmission of SARS-CoV-2 in farmed minks and associated humans in the Netherlands. Nat Commun. 2021 Nov 23;12(1):6802. https://doi.org/10.1038/s41467-021-27096-9

20. Su C, He J, Han P, Bai B, Li D, Cao J et al. Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants. J Virol. 2022 Sep 14;96(17):e0081422. https://doi.org/10.1128/jvi.00814-22

21. Feng Y, Su Q, Li L, He X, Niu P, Guo X et al. Genomic Surveillance for SARS-CoV-2 Variants: Dominance of XBB Replacement - China, January-June 2023. China CDC Wkly. 2024 Apr 12;6(15):324-331. https://doi.org/10.46234/ccdcw2024.061

22. Zaki N, Mohamed EA. The estimations of the COVID-19 incubation period: A scoping reviews of the literature. J Infect Public Health. 2021 May;14(5):638-646. https://doi.org/10.1016/j.jiph.2021.01.019

23. Quesada JA, López-Pineda A, Gil-Guillén VF, Arriero-Marín JM, Gutiérrez F, Carratala-Munuera C. Incubation period of COVID-19: A systematic review and meta-analysis. Rev Clin Esp (Barc). 2021 Feb;221(2):109-117. https://doi.org/10.1016/j.rceng.2020.08.002

24. Kandel C, Lee Y, Taylor M, Llanes A, McCready J, Crowl G et al. Viral dynamics of the SARS-CoV-2 Omicron Variant among household contacts with 2 or 3 COVID-19 vaccine doses. J Infect. 2022 Dec;85(6):666-670. https://doi.org/10.1016/j.jinf.2022.10.027

25. Burkholz S, Pokhrel S, Kraemer BR, Mochly-Rosen D, Carback RT 3rd, Hodge T et al. Paired SARS-CoV-2 spike protein mutations observed during ongoing SARS-CoV-2 viral transfer from humans to minks and back to humans. Infect Genet Evol. 2021 Sep;93:104897. https://doi.org/10.1016/j.meegid.2021.104897

26. Greaney AJ, Starr TN, Gilchuk P, Zost SJ, Binshtein E, Loes AN et al. Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition. Cell Host Microbe. 2021 Jan 13;29(1):44-57.e9. https://doi.org/10.1016/j.chom.2020.11.007

27. Yang Y, Guo L, Yuan J, Xu Z, Gu Y, Zhang J et al. Viral and antibody dynamics of acute infection with SARS-CoV-2 omicron variant (B.1.1.529): a prospective cohort study from Shenzhen, China. Lancet Microbe. 2023 Aug;4(8):e632-e641. https://doi.org/10.1016/S2666-5247(23)00139-8. Epub 2023 Jul 14. Erratum in: Lancet Microbe. 2023 Aug;4(8):e576. https://doi.org/10.1016/S2666-5247(23)00223-9

28. Almehdi AM, Khoder G, Alchakee AS, Alsayyid AT, Sarg NH, Soliman SSM. SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies. Infection. 2021 Oct;49(5):855-876. https://doi.org/10.1007/s15010-021-01677-8 Epub 2021 Aug 2.

29. Du Y, Wang H, Chen L, Fang Q, Zhang B, Jiang L, Wu Z, Yang Y, Zhou Y, Chen B, Lyu J, Wang Z. Non-RBM Mutations Impaired SARS-CoV-2 Spike Protein Regulated to the ACE2 Receptor Based on Molecular Dynamic Simulation. Front Mol Biosci. 2021 Jul 27;8:614443. https://doi.org/10.3389/fmolb.2021.614443

Downloads

Published

2025-09-15

Issue

Section

Articles

How to Cite

(1)
Tifonova, I.; Lazarova , L. .; Tchakarova, S.; Donchev , D. .; Stoikov , . I. .; Grigorova , L. .; Ivanov, I. . .; Alexiev , I. .; Korsun , N. .; Christova , I. . TRACKING TWO-WAY HUMAN-MINK TRANSMISSION DURING AN OUTBREAK OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 ON A FARM IN BULGARIA. Probl Infect Parasit Dis 2025, 53 (2), 19-26. https://doi.org/10.58395/10vta464.

Most read articles by the same author(s)

1 2 3 > >>