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Experimental Transmission Studies of SARS-CoV-2 in Fruit Bats, Ferrets, Pigs and Chickens

39 Pages Posted: 8 May 2020

See all articles by Kore Schlottau

Kore Schlottau

World Health Organization - Institute of Diagnostic Virology

Melanie Rissmann

World Health Organization - Institute of Novel and Emerging Infectious Diseases

Annika Graaf

World Health Organization - Institute of Diagnostic Virology

Jacob Schön

World Health Organization - Institute of Diagnostic Virology

Julia Sehl

World Health Organization - Department of Experimental Animal Facilities and Biorisk Managment

Claudia Wylezich

World Health Organization - Institute of Diagnostic Virology

Dirk Höper

World Health Organization - Institute of Diagnostic Virology

Thomas C. Mettenleiter

World Health Organization - Friedrich-Loeffler-Institut

Anne Balkema-Buschmann

World Health Organization - Institute of Novel and Emerging Infectious Diseases

Timm Harder

World Health Organization - Institute of Diagnostic Virology

Christian Grund

World Health Organization - Institute of Diagnostic Virology

Donata Hoffmann

World Health Organization - Institute of Diagnostic Virology

Angele Breithaupt

World Health Organization - Department of Experimental Animal Facilities and Biorisk Managment

Martin Beer

World Health Organization - Institute of Diagnostic Virology

More...

Abstract

Background: A novel zoonotic SARS-related coronavirus emerged in China at the end of 2019. The novel SARS-CoV-2 became pandemic within weeks and the number of human infections and severe cases is increasing. The role of potential animal hosts is still understudied.

Methods: We intranasally inoculated fruit bats (Rousettus aegyptiacus; n=9), ferrets (n=9), pigs (n=9) and chickens (n=17) with 105 TCID50 of a SARS-CoV-2 isolate per animal. Animals were monitored clinically and for virus shedding. Direct contact animals (n=3) were included. Animals were humanely sacrificed for virological and immune-pathohistological analysis at different time points.

Findings: Under these settings, pigs and chickens were not susceptible to SARS-CoV-2. All swabs as well as organ samples and contact animals remained negative for viral RNA, and none of the animals seroconverted. Rousettus aegyptiacus fruit bats experienced a transient infection, with virus detectable by RT-qPCR, immunohistochemistry (IHC) and in situ hybridization (ISH) in the nasal cavity, associated with rhinitis. Viral RNA was also identified in the trachea, lung and lung associated lymphatic tissue. One of three contact bats became infected. More efficient virus replication but no clinical signs were observed in ferrets with transmission to all direct contact animals. Prominent viral RNA loads of up to 104 viral genome copies/ml were detected in the upper respiratory tract. Mild rhinitis was associated with viral antigen detection in the respiratory and olfactory epithelium. Both fruit bats and ferrets developed SARS-CoV-2 reactive antibodies reaching neutralizing titers of up to 1:1024.

Interpretation: Pigs and chickens could not be infected intranasally by SARS-CoV-2, whereas fruit bats showed characteristics of a reservoir host. Virus replication in ferrets resembled a subclinical human infection with efficient spread. These animals might serve as a useful model for further studies e.g. testing vaccines or antivirals.

Funding Statement: Intramural funding of the German Federal Ministry of Food and Agriculture provided to the Friedrich-Loeffler-Institut.

Declaration of Interests: All authors declare no competing interest.

Ethics Approval Statement: The animal experiments were evaluated and approved by the ethics committee of the State Office of Agriculture, Food safety, and Fishery in Mecklenburg – Western Pomerania (LALLF M-V: LVL MV/TSD/7221.3-2-010/18-12). All procedures were carried out in approved biosafety level 3 (BSL3) facilities.

Keywords: SARS-CoV-2; animal model; Rousettus fruit bat; ferret; pig; chicken

Suggested Citation

Schlottau, Kore and Rissmann, Melanie and Graaf, Annika and Schön, Jacob and Sehl, Julia and Wylezich, Claudia and Höper, Dirk and Mettenleiter, Thomas C. and Balkema-Buschmann, Anne and Harder, Timm and Grund, Christian and Hoffmann, Donata and Breithaupt, Angele and Beer, Martin, Experimental Transmission Studies of SARS-CoV-2 in Fruit Bats, Ferrets, Pigs and Chickens (4/15/2020). Available at SSRN: https://ssrn.com/abstract=3578792 or http://dx.doi.org/10.2139/ssrn.3578792

Kore Schlottau (Contact Author)

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Melanie Rissmann

World Health Organization - Institute of Novel and Emerging Infectious Diseases

Greifswald-Insel Riems
Germany

Annika Graaf

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Jacob Schön

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Julia Sehl

World Health Organization - Department of Experimental Animal Facilities and Biorisk Managment

Greifswald-Insel Riems
Germany

Claudia Wylezich

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Dirk Höper

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Thomas C. Mettenleiter

World Health Organization - Friedrich-Loeffler-Institut

Greifswald-Insel Riems
Germany

Anne Balkema-Buschmann

World Health Organization - Institute of Novel and Emerging Infectious Diseases

Greifswald-Insel Riems
Germany

Timm Harder

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Christian Grund

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Donata Hoffmann

World Health Organization - Institute of Diagnostic Virology

Greifswald-Insel Riems
Germany

Angele Breithaupt

World Health Organization - Department of Experimental Animal Facilities and Biorisk Managment ( email )

Greifswald-Insel Riems
Germany

Martin Beer

World Health Organization - Institute of Diagnostic Virology ( email )

Greifswald-Insel Riems
Germany

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