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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

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. parti...

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Autores principales: Cross, Robert W., Agans, Krystle N., Prasad, Abhishek N., Borisevich, Viktoriya, Woolsey, Courtney, Deer, Daniel J., Dobias, Natalie S., Geisbert, Joan B., Fenton, Karla A., Geisbert, Thomas W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431901/
https://www.ncbi.nlm.nih.gov/pubmed/32811514
http://dx.doi.org/10.1186/s12985-020-01396-w
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author Cross, Robert W.
Agans, Krystle N.
Prasad, Abhishek N.
Borisevich, Viktoriya
Woolsey, Courtney
Deer, Daniel J.
Dobias, Natalie S.
Geisbert, Joan B.
Fenton, Karla A.
Geisbert, Thomas W.
author_facet Cross, Robert W.
Agans, Krystle N.
Prasad, Abhishek N.
Borisevich, Viktoriya
Woolsey, Courtney
Deer, Daniel J.
Dobias, Natalie S.
Geisbert, Joan B.
Fenton, Karla A.
Geisbert, Thomas W.
author_sort Cross, Robert W.
collection PubMed
description 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.
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spelling pubmed-74319012020-08-18 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 Cross, Robert W. Agans, Krystle N. Prasad, Abhishek N. Borisevich, Viktoriya Woolsey, Courtney Deer, Daniel J. Dobias, Natalie S. Geisbert, Joan B. Fenton, Karla A. Geisbert, Thomas W. Virol J Short Report 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. BioMed Central 2020-08-18 /pmc/articles/PMC7431901/ /pubmed/32811514 http://dx.doi.org/10.1186/s12985-020-01396-w Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Cross, Robert W.
Agans, Krystle N.
Prasad, Abhishek N.
Borisevich, Viktoriya
Woolsey, Courtney
Deer, Daniel J.
Dobias, Natalie S.
Geisbert, Joan B.
Fenton, Karla A.
Geisbert, Thomas W.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431901/
https://www.ncbi.nlm.nih.gov/pubmed/32811514
http://dx.doi.org/10.1186/s12985-020-01396-w
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