Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells and Viruses
2.2. In Vivo Study
2.3. Viral RNA Isolation and Real-Time RT-qPCR
2.4. Whole Genome Sequencing
2.5. Serology
2.6. Histopathology, Immunohistochemistry and In Situ Hybridisation
2.7. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020, 395, 565–574. [Google Scholar] [CrossRef] [Green Version]
- WHO. Coronavirus Disease (COVID-19) Dashboard; WHO: Geneva, Switzerland; Available online: https://covid19.who.int/?gclid=Cj0KCQjw6PD3BRDPARIsAN8pHuGW7gnuISkwhrrTFGyXHC9iezAHQb_uCFIkZk3p_5FFY4Wz81kkBHoaAiMqEALw_wcB (accessed on 1 December 2020).
- Buitrago-Garcia, D.; Egli-Gany, D.; Counotte, M.J.; Hossmann, S.; Imeri, H.; Ipekci, A.M.; Salanti, G.; Low, N. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis. PLoS Med. 2020, 17, e1003346. [Google Scholar] [CrossRef] [PubMed]
- Cui, J.; Li, F.; Shi, Z.L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 2019, 17, 181–192. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Santini, J.M.; Edwards, S.J.L. Host range of SARS-CoV-2 and implications for public health. Lancet Microbe 2020. [Google Scholar] [CrossRef]
- Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Kruger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020, 181, 271–280. [Google Scholar] [CrossRef]
- Irigoyen, N.; Firth, A.E.; Jones, J.D.; Chung, B.Y.; Siddell, S.G.; Brierley, I. High-resolution analysis of coronavirus gene expression by RNA sequencing and ribosome profiling. PLoS Pathog. 2016, 12, e1005473. [Google Scholar] [CrossRef] [Green Version]
- Kim, Y.I.; Kim, S.G.; Kim, S.M.; Kim, E.H.; Park, S.J.; Yu, K.M.; Chang, J.H.; Kim, E.J.; Lee, S.; Casel, M.A.B.; et al. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe 2020. [Google Scholar] [CrossRef]
- Shi, J.; Wen, Z.; Zhong, G.; Yang, H.; Wang, C.; Huang, B.; Liu, R.; He, X.; Shuai, L.; Sun, Z.; et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science 2020. [Google Scholar] [CrossRef] [Green Version]
- Sia, S.F.; Yan, L.M.; Chin, A.W.H.; Fung, K.; Choy, K.T.; Wong, A.Y.L.; Kaewpreedee, P.; Perera, R.; Poon, L.L.M.; Nicholls, J.M.; et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 2020. [Google Scholar] [CrossRef]
- Richard, M.; Kok, A.; de Meulder, D.; Bestebroer, T.M.; Lamers, M.M.; Okba, N.M.A.; Fentener van Vlissingen, M.; Rockx, B.; Haagmans, B.L.; Koopmans, M.P.G.; et al. SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nat. Commun. 2020, 11, 3496. [Google Scholar] [CrossRef]
- Halfmann, P.J.; Hatta, M.; Chiba, S.; Maemura, T.; Fan, S.; Takeda, M.; Kinoshita, N.; Hattori, S.I.; Sakai-Tagawa, Y.; Iwatsuki-Horimoto, K.; et al. Transmission of SARS-CoV-2 in domestic cats. N. Engl. J. Med. 2020, 383, 592–594. [Google Scholar] [CrossRef] [PubMed]
- Chan, J.F.; Zhang, A.J.; Yuan, S.; Poon, V.K.; Chan, C.C.; Lee, A.C.; Chan, W.M.; Fan, Z.; Tsoi, H.W.; Wen, L.; et al. Simulation of the clinical and pathological manifestations of coronavirus disease 2019 (COVID-19) in a golden syrian hamster model: Implications for disease pathogenesis and transmissibility. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2020, 71, 2428–2446. [Google Scholar] [CrossRef] [PubMed]
- Munster, V.J.; Feldmann, F.; Williamson, B.N.; van Doremalen, N.; Pérez-Pérez, L.; Schulz, J.; Meade-White, K.; Okumura, A.; Callison, J.; Brumbaugh, B.; et al. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature 2020, 585, 268–272. [Google Scholar] [CrossRef] [PubMed]
- Rockx, B.; Kuiken, T.; Herfst, S.; Bestebroer, T.; Lamers, M.M.; Oude Munnink, B.B.; de Meulder, D.; van Amerongen, G.; van den Brand, J.; Okba, N.M.A.; et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science 2020, 368, 1012–1015. [Google Scholar] [CrossRef] [Green Version]
- Woolsey, C.; Borisevich, V.; Prasad, A.N.; Agans, K.N.; Deer, D.J.; Dobias, N.S.; Heymann, J.C.; Foster, S.L.; Levine, C.B.; Medina, L.; et al. Establishment of an African green monkey model for COVID-19. Nat. Immunol. 2021, 22, 86–98. [Google Scholar] [CrossRef]
- Schlottau, K.; Rissmann, M.; Graaf, A.; Schön, J.; Sehl, J.; Wylezich, C.; Höper, D.; Mettenleiter, T.C.; Balkema-Buschmann, A.; Harder, T.; et al. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: An experimental transmission study. Lancet Microbe 2020, 1, e218–e225. [Google Scholar] [CrossRef]
- Zhao, Y.; Wang, J.; Kuang, D.; Xu, J.; Yang, M.; Ma, C.; Zhao, S.; Li, J.; Long, H.; Ding, K.; et al. Susceptibility of tree shrew to SARS-CoV-2 infection. Sci. Rep. 2020, 10, 16007. [Google Scholar] [CrossRef]
- Suarez, D.L.; Pantin-Jackwood, M.J.; Swayne, D.E.; Lee, S.A.; DeBlois, S.M.; Spackman, E. Lack of susceptibility to SARS-CoV-2 and MERS-CoV in poultry. Emerg. Infect. Dis. 2020, 26, 3074–3076. [Google Scholar] [CrossRef]
- Oreshkova, N.; Molenaar, R.J.; Vreman, S.; Harders, F.; Oude Munnink, B.B.; Hakze-van der Honing, R.W.; Gerhards, N.; Tolsma, P.; Bouwstra, R.; Sikkema, R.S.; et al. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Eurosurveillance 2020, 25, 2001005. [Google Scholar] [CrossRef]
- ProMED. Coronavirus Disease 2019 Update (281): Netherlands (North Brabant, Limburg) Farmed Mink, Spread, Animal, Global. Available online: https://promedmail.org/promed-post/?id=20200623.7502849 (accessed on 29 June 2020).
- ProMED. Coronavirus Disease 2019 Update (284): Denmark (North Jutland) Animal, Farmed Mink, Spread, Dog. Available online: https://promedmail.org/promed-post/?id=7506728 (accessed on 29 June 2020).
- Oude Munnink, B.B.; Sikkema, R.S.; Nieuwenhuijse, D.F.; Molenaar, R.J.; Munger, E.; Molenkamp, R.; van der Spek, A.; Tolsma, P.; Rietveld, A.; Brouwer, M.; et al. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science 2020. [Google Scholar] [CrossRef]
- OIE. COVID-19 Portal. Available online: https://www.oie.int/en/scientific-expertise/specific-information-and-recommendations/questions-and-answers-on-2019novel-coronavirus/events-in-animals/ (accessed on 1 December 2020).
- Muñoz-Fontela, C.; Dowling, W.E.; Funnell, S.G.P.; Gsell, P.-S.; Riveros-Balta, A.X.; Albrecht, R.A.; Andersen, H.; Baric, R.S.; Carroll, M.W.; Cavaleri, M.; et al. Animal models for COVID-19. Nature 2020, 586, 509–515. [Google Scholar] [CrossRef] [PubMed]
- Chu, Y.K.; Ali, G.D.; Jia, F.; Li, Q.; Kelvin, D.; Couch, R.C.; Harrod, K.S.; Hutt, J.A.; Cameron, C.; Weiss, S.R.; et al. The SARS-CoV ferret model in an infection-challenge study. Virology 2008, 374, 151–163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ryan, K.A.; Bewley, K.R.; Fotheringham, S.A.; Slack, G.S.; Brown, P.; Hall, Y.; Wand, N.I.; Marriott, A.C.; Cavell, B.E.; Tree, J.A.; et al. Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity. Nat. Commun. 2021, 12, 81. [Google Scholar] [CrossRef] [PubMed]
- Karber, G. Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Arch Exp. Path Pharmakol 1931, 162, 480–483. [Google Scholar] [CrossRef]
- Reed, L.J.; Muench, H. A simple method of estimating fifty per cent endpoints. Am. J. Epidemiol. 1938, 27, 493–497. [Google Scholar] [CrossRef]
- Spearman, C. The method of right and wrong cases (constant stimuli) without Gauss’s formulae. Br. J. Psychol. 1908, 2, 227. [Google Scholar] [CrossRef]
- Percie du Sert, N.; Hurst, V.; Ahluwalia, A.; Alam, S.; Avey, M.T.; Baker, M.; Browne, W.J.; Clark, A.; Cuthill, I.C.; Dirnagl, U.; et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. BMC Vet. Res. 2020, 16, 242. [Google Scholar] [CrossRef]
- Caly, L.; Druce, J.; Roberts, J.; Bond, K.; Tran, T.; Kostecki, R.; Yoga, Y.; Naughton, W.; Taiaroa, G.; Seemann, T.; et al. Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia. Med. J. Aust. 2020. [Google Scholar] [CrossRef] [Green Version]
- Corman, V.M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D.K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M.L.; et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. Bull. Eur. Mal. Transm. Eur. Commun. Dis. Bull. 2020, 25. [Google Scholar] [CrossRef] [Green Version]
- Lewandowski, K.; Xu, Y.; Pullan, S.T.; Lumley, S.F.; Foster, D.; Sanderson, N.; Vaughan, A.; Morgan, M.; Bright, N.; Kavanagh, J.; et al. Metagenomic nanopore sequencing of influenza virus direct from clinical respiratory samples. J. Clin. Microbiol. 2019, 58. [Google Scholar] [CrossRef] [Green Version]
- Katoh, K.; Standley, D.M. MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Mol. Biol. Evol. 2013, 30, 772–780. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kumar, S.; Stecher, G.; Li, M.; Knyaz, C.; Tamura, K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol. 2018, 35, 1547–1549. [Google Scholar] [CrossRef] [PubMed]
- Lean, F.Z.X.; Lamers, M.M.; Smith, S.P.; Shipley, R.; Schipper, D.; Temperton, N.; Haagmans, B.L.; Banyard, A.C.; Bewley, K.R.; Carroll, M.W.; et al. Development of immunohistochemistry and in situ hybridisation for the detection of SARS-CoV and SARS-CoV-2 in formalin-fixed paraffin-embedded specimens. Sci. Rep. 2020, 10, 21894. [Google Scholar] [CrossRef] [PubMed]
- Bao, L.; Deng, W.; Gao, H.; Xiao, C.; Liu, J.; Xue, J.; Lv, Q.; Liu, J.; Yu, P.; Xu, Y.; et al. Lack of reinfection in RHESUS Macaques Infected with SARS-CoV-2. bioRxiv 2020. [Google Scholar] [CrossRef] [Green Version]
- van den Brand, J.M.; Haagmans, B.L.; van Riel, D.; Osterhaus, A.D.; Kuiken, T. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J. Comp. Pathol. 2014, 151, 83–112. [Google Scholar] [CrossRef] [Green Version]
- Damas, J.; Hughes, G.M.; Keough, K.C.; Painter, C.A.; Persky, N.S.; Corbo, M.; Hiller, M.; Koepfli, K.-P.; Pfenning, A.R.; Zhao, H.; et al. Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. Proc. Natl. Acad. Sci. USA 2020, 117, 22311. [Google Scholar] [CrossRef]
- Lechien, J.R.; Chiesa-Estomba, C.M.; De Siati, D.R.; Horoi, M.; Le Bon, S.D.; Rodriguez, A.; Dequanter, D.; Blecic, S.; El Afia, F.; Distinguin, L.; et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study. Eur. Arch. Otorhinolaryngol. 2020, 277, 2251–2261. [Google Scholar] [CrossRef]
- Xydakis, M.S.; Dehgani-Mobaraki, P.; Holbrook, E.H.; Geisthoff, U.W.; Bauer, C.; Hautefort, C.; Herman, P.; Manley, G.T.; Lyon, D.M.; Hopkins, C. Smell and taste dysfunction in patients with COVID-19. Lancet Infect. Dis. 2020. [Google Scholar] [CrossRef]
- Tong, J.Y.; Wong, A.; Zhu, D.; Fastenberg, J.H.; Tham, T. The prevalence of olfactory and gustatory dysfunction in COVID-19 patients: A systematic review and meta-analysis. Otolaryngol. Head Neck Surg. 2020. [Google Scholar] [CrossRef]
- Meinhardt, J.; Radke, J.; Dittmayer, C.; Franz, J.; Thomas, C.; Mothes, R.; Laue, M.; Schneider, J.; Brünink, S.; Greuel, S.; et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci. 2020. [Google Scholar] [CrossRef]
- Koyama, T.; Platt, D.; Parida, L. Variant analysis of SARS-CoV-2 genomes. Bull. World Health Organ. 2020, 98, 495–504. [Google Scholar] [CrossRef] [PubMed]
- Baum, A.; Fulton, B.O.; Wloga, E.; Copin, R.; Pascal, K.E.; Russo, V.; Giordano, S.; Lanza, K.; Negron, N.; Ni, M.; et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 2020. [Google Scholar] [CrossRef] [PubMed]
- Hayashi, T.; Yaegashi, N.; Konishi, I. Effect of RBD mutation (Y453F) in spike glycoprotein of SARS-CoV-2 on neutralizing antibody affinity. bioRxiv 2020. [Google Scholar] [CrossRef]
- Starr, T.N.; Greaney, A.J.; Hilton, S.K.; Ellis, D.; Crawford, K.H.D.; Dingens, A.S.; Navarro, M.J.; Bowen, J.E.; Tortorici, M.A.; Walls, A.C.; et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 2020, 182, 1295–1310. [Google Scholar] [CrossRef] [PubMed]
- Piplani, S.; Singh, P.K.; Winkler, D.A.; Petrovsky, N. In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus. arXiv 2020, arXiv:2005.06199. [Google Scholar]
- Zhang, L.; Jackson, C.B.; Mou, H.; Ojha, A.; Peng, H.; Quinlan, B.D.; Rangarajan, E.S.; Pan, A.; Vanderheiden, A.; Suthar, M.S.; et al. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat. Commun. 2020, 11, 6013. [Google Scholar] [CrossRef]
- Korber, B.; Fischer, W.M.; Gnanakaran, S.; Yoon, H.; Theiler, J.; Abfalterer, W.; Hengartner, N.; Giorgi, E.E.; Bhattacharya, T.; Foley, B.; et al. Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus. Cell 2020, 182, 812–827. [Google Scholar] [CrossRef]
- Hou, Y.J.; Chiba, S.; Halfmann, P.; Ehre, C.; Kuroda, M.; Dinnon, K.H.; Leist, S.R.; Schäfer, A.; Nakajima, N.; Takahashi, K.; et al. SARS-CoV-2 D614G variant exhibits enhanced replication ex vivo and earlier transmission in vivo. Science 2020, 370, 1464–1468. [Google Scholar] [CrossRef]
- Zhou, B.; Thao, T.T.N.; Hoffmann, D.; Taddeo, A.; Ebert, N.; Labroussaa, F.; Pohlmann, A.; King, J.; Portmann, J.; Halwe, N.J.; et al. SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility. bioRxiv 2020. [Google Scholar] [CrossRef]
- McAuley, A.J.; Kuiper, M.J.; Durr, P.A.; Bruce, M.P.; Barr, J.; Todd, S.; Au, G.G.; Blasdell, K.; Tachedjian, M.; Lowther, S.; et al. Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein. NPJ Vaccines 2020, 5, 96. [Google Scholar] [CrossRef]
- Long, Q.-X.; Tang, X.-J.; Shi, Q.-L.; Li, Q.; Deng, H.-J.; Yuan, J.; Hu, J.-L.; Xu, W.; Zhang, Y.; Lv, F.-J.; et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat. Med. 2020. [Google Scholar] [CrossRef] [PubMed]
- Robbiani, D.F.; Gaebler, C.; Muecksch, F.; Lorenzi, J.C.C.; Wang, Z.; Cho, A.; Agudelo, M.; Barnes, C.O.; Gazumyan, A.; Finkin, S.; et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 2020. [Google Scholar] [CrossRef] [PubMed]
- Kutter, J.S.; de Meulder, D.; Bestebroer, T.M.; Lexmond, P.; Mulders, A.; Fouchier, R.A.; Herfst, S. SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance. bioRxiv 2020. [Google Scholar] [CrossRef]
- Ong, S.W.X.; Tan, Y.K.; Chia, P.Y.; Lee, T.H.; Ng, O.T.; Wong, M.S.Y.; Marimuthu, K. Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) from a symptomatic patient. JAMA 2020, 323, 1610–1612. [Google Scholar] [CrossRef] [Green Version]
- Gandhi, M.; Yokoe, D.S.; Havlir, D.V. Asymptomatic transmission, the achilles’ heel of current strategies to control Covid-19. N. Engl. J. Med. 2020, 382, 2158–2160. [Google Scholar] [CrossRef]
Dpi a | Inoculation | Weight | Temperature | Nasal Wash | Throat Swab | Rectal Swab | Blood | Environmental/Fur | Necropsy |
---|---|---|---|---|---|---|---|---|---|
–8 | x | x | |||||||
–7 | x | ||||||||
–6 | x | ||||||||
–5 | x | ||||||||
−4 | x | x | |||||||
–3 | x | x | |||||||
–2 | x | x | |||||||
–1 | x | x | x | ||||||
0 | X (n = 12) | x | x | x | x | x | |||
1 | x | x | |||||||
2 | x | x | x | x | x | x | |||
3 | x | x | 2 ferrets | ||||||
4 | x | x | x | x | x | x | x | ||
5 | x | x | 2 ferrets | ||||||
6 | x | x | x | x | x | x | |||
7 | x | x | 2 ferrets | ||||||
8 | x | x | x | x | x | x | x | ||
9 | x | x | |||||||
10 | x | x | x | x | x | x | |||
11 | x | x | |||||||
12 | x | x | |||||||
13 | x | x | |||||||
14 | x | x | x | x | x | x | x | 2 ferrets | |
15 | x | x | |||||||
16 | x | x | |||||||
17 | Re-challenged (n = 2) | x | x | x | x | x | x | ||
18 | 1 | x | x | ||||||
19 | 2 | x | x | x | x | x | |||
20 | 3 | x | x | ||||||
21 | 4 | x | x | x | x | x | x | x | 2 ferrets |
5 | |||||||||
6 | |||||||||
7 | x | x | x | x | x | x | x | Re-challenged 2 ferrets |
Sample (Ferret ID, dpi, sample) | VI-Positive (+) or VI-Negative (−) |
---|---|
Nasal Washes | |
19243 4 dpi Nasal Wash | − |
19517 4 dpi Nasal Wash | − |
99873 4 dpi Nasal Wash | + |
19659 4 dpi Nasal Wash | − |
19675 4 dpi Nasal Wash | + |
00396 4 dpi Nasal Wash | − |
00479 4 dpi Nasal Wash | − |
18784 4 dpi Nasal Wash | − |
18988 4 dpi Nasal Wash | − |
19413 4 dpi Nasal Wash | − |
19517 6 dpi Nasal Wash | − |
99873 6 dpi Nasal Wash | − |
19659 6 dpi Nasal Wash | + |
19675 6 dpi Nasal Wash | + |
00479 6 dpi Nasal Wash | − |
18784 6 dpi Nasal Wash | − |
18988 6 dpi Nasal Wash | − |
19413 6 dpi Nasal Wash | − |
19517 7 dpi Nasal Wash | + |
00479 7 dpi Nasal Wash | − |
Tissues | |
19517 7 dpi Soft Palate | − |
19517 7 dpi Respiratory Turbinate | + |
19517 7 dpi Larynx | + |
19517 7 dpi Stomach | − |
19517 7 dpi Oesophagus | + |
00396 5 dpi Respiratory Turbinate | + |
00002 3 dpi Respiratory Turbinate | − |
00002 3 dpi Oesophagus | ND * |
19243 5 dpi Brain | ND * |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Everett, H.E.; Lean, F.Z.X.; Byrne, A.M.P.; van Diemen, P.M.; Rhodes, S.; James, J.; Mollett, B.; Coward, V.J.; Skinner, P.; Warren, C.J.; et al. Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection. Viruses 2021, 13, 113. https://doi.org/10.3390/v13010113
Everett HE, Lean FZX, Byrne AMP, van Diemen PM, Rhodes S, James J, Mollett B, Coward VJ, Skinner P, Warren CJ, et al. Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection. Viruses. 2021; 13(1):113. https://doi.org/10.3390/v13010113
Chicago/Turabian StyleEverett, Helen E., Fabian Z. X. Lean, Alexander M. P. Byrne, Pauline M. van Diemen, Shelley Rhodes, Joe James, Benjamin Mollett, Vivien J. Coward, Paul Skinner, Caroline J. Warren, and et al. 2021. "Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection" Viruses 13, no. 1: 113. https://doi.org/10.3390/v13010113