See the published version of this article at Virology Journal.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Short report
Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase
Thomas W Geisbert
University of Texas Medical Branch
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0858-1877
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Virology Journal.
We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.
Keywords
Coronavirus, SARS-CoV-2, COVID-19, nonhuman primate, animal models
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- SUPPLEMENTARYFIGURE1TEMPERATURE.tif
Supplementary Figure 1: Longitudinal temperature monitoring of SARS-CoV-2 infected AGMs. Temperature was longitudinally monitored for all animals via surgically-implanted temperature loggers (see Materials and methods). Data shown for all animals begins 1 day prior to infection (-1) and terminates in the morning of day 5 post-infection, when AGM-1, AGM-2, and AGM-3 were euthanized. Periods of elevated temperature are indicated in red. Arrows denote time of challenge.
- SupplemenaryTable1.docx
Supplementary Table 1: Clinical description and outcome of African green monkeys following SARS-CoV-2 challenge.
- SupplementaryTable2Revised.docx
Supplementary Table 2: Gross lung lesion severity scores in AGMs infected with SARS-CoV-2
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 13 Aug, 2020
Published
On 18 Aug, 2020
No community comments so far
Editor assigned
On 07 Aug, 2020
Editorial decision: Accept
On 07 Aug, 2020
Submission checks complete
On 06 Aug, 2020
Editor invited
On 06 Aug, 2020
No comments provided
Reviewer #2 agreed
On 30 Jul, 2020
Editor assigned
On 29 Jul, 2020
Reviewers invited
Invitations sent on 29 Jul, 2020
Reviewer #1 agreed
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
First submitted
On 27 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Virology
Learn more about our company.
This preprint is under consideration at Virology Journal. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Short report
Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase
Thomas W Geisbert
University of Texas Medical Branch
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0858-1877
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 13 Aug, 2020
Published
On 18 Aug, 2020
No community comments so far
Editor assigned
On 07 Aug, 2020
Editorial decision: Accept
On 07 Aug, 2020
Submission checks complete
On 06 Aug, 2020
Editor invited
On 06 Aug, 2020
No comments provided
Reviewer #2 agreed
On 30 Jul, 2020
Editor assigned
On 29 Jul, 2020
Reviewers invited
Invitations sent on 29 Jul, 2020
Reviewer #1 agreed
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
First submitted
On 27 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Virology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Virology Journal.
We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5