SARS-CoV-2 viral dynamics in non-human primates

Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large b...

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Published in:PLoS computational biology 2021-03, Vol.17 (3), p.e1008785-e1008785
Main Authors: Gonçalves, Antonio, Maisonnasse, Pauline, Donati, Flora, Albert, Mélanie, Behillil, Sylvie, Contreras, Vanessa, Naninck, Thibaut, Marlin, Romain, Solas, Caroline, Pizzorno, Andres, Lemaitre, Julien, Kahlaoui, Nidhal, Terrier, Olivier, Ho Tsong Fang, Raphael, Enouf, Vincent, Dereuddre-Bosquet, Nathalie, Brisebarre, Angela, Touret, Franck, Chapon, Catherine, Hoen, Bruno, Lina, Bruno, Rosa Calatrava, Manuel, de Lamballerie, Xavier, Mentré, France, Le Grand, Roger, van der Werf, Sylvie, Guedj, Jérémie
Format: Article
Language:English
Subjects:
Analysis
Animals
Antiviral Agents
Antiviral Agents - pharmacology
Basic Reproduction Number
Biology and Life Sciences
COVID-19
COVID-19 - blood
COVID-19 - prevention & control
COVID-19 - virology
Cytokines
Cytokines - blood
Disease Models, Animal
Disease prevention
Dosage
Dynamic models
Health aspects
Infections
Influenza
Laboratory animals
Life Sciences
Macaca fascicularis
Macaca fascicularis - virology
Macaques
Medicine and Health Sciences
Microbiology and Parasitology
Model testing
Nasopharynx
Nasopharynx - virology
Normal distribution
Parameter estimation
Physiological aspects
Prophylaxis
SARS-CoV-2
SARS-CoV-2 - drug effects
SARS-CoV-2 - physiology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Standard deviation
Trachea
Trachea - virology
Upper bounds
Viral diseases
Viral Load
Virology
Virus diseases
Virus Replication
Virus Replication - drug effects
Viruses
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cited_by cdi_FETCH-LOGICAL-c699t-fc31cb31ea222e2885c08b32965b65800836ee9316baea6091a635c2f031e0743
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container_title PLoS computational biology
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creator Gonçalves, Antonio
Maisonnasse, Pauline
Donati, Flora
Albert, Mélanie
Behillil, Sylvie
Contreras, Vanessa
Naninck, Thibaut
Marlin, Romain
Solas, Caroline
Pizzorno, Andres
Lemaitre, Julien
Kahlaoui, Nidhal
Terrier, Olivier
Ho Tsong Fang, Raphael
Enouf, Vincent
Dereuddre-Bosquet, Nathalie
Brisebarre, Angela
Touret, Franck
Chapon, Catherine
Hoen, Bruno
Lina, Bruno
Rosa Calatrava, Manuel
de Lamballerie, Xavier
Mentré, France
Le Grand, Roger
van der Werf, Sylvie
Guedj, Jérémie
description Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (>104 virus) and a within-host reproductive basic number of approximately 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly lost with a half-life of 9 hours, with no significant association between cytokine elevation and clearance, leading to a median time to viral clearance of 10 days, consistent with observations in mild human infections. Given these parameter estimates, we predict that a prophylactic treatment blocking 90% of viral production or viral infection could prevent viral growth. In conclusion, our results provide estimates of SARS-CoV-2 viral kinetic parameters in an experimental model of mild infection and they provide means to assess the efficacy of future antiviral treatments.
doi_str_mv 10.1371/JOURNAL.PCBI.1008785
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viral dynamics in non-human primates</title><author>Gonçalves, Antonio ; Maisonnasse, Pauline ; Donati, Flora ; Albert, Mélanie ; Behillil, Sylvie ; Contreras, Vanessa ; Naninck, Thibaut ; Marlin, Romain ; Solas, Caroline ; Pizzorno, Andres ; Lemaitre, Julien ; Kahlaoui, Nidhal ; Terrier, Olivier ; Ho Tsong Fang, Raphael ; Enouf, Vincent ; Dereuddre-Bosquet, Nathalie ; Brisebarre, Angela ; Touret, Franck ; Chapon, Catherine ; Hoen, Bruno ; Lina, Bruno ; Rosa Calatrava, Manuel ; de Lamballerie, Xavier ; Mentré, France ; Le Grand, Roger ; van der Werf, Sylvie ; Guedj, Jérémie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c699t-fc31cb31ea222e2885c08b32965b65800836ee9316baea6091a635c2f031e0743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antiviral Agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Basic Reproduction Number</topic><topic>Biology and Life Sciences</topic><topic>COVID-19</topic><topic>COVID-19 - blood</topic><topic>COVID-19 - prevention &amp; control</topic><topic>COVID-19 - virology</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Disease Models, Animal</topic><topic>Disease prevention</topic><topic>Dosage</topic><topic>Dynamic models</topic><topic>Health aspects</topic><topic>Infections</topic><topic>Influenza</topic><topic>Laboratory animals</topic><topic>Life Sciences</topic><topic>Macaca fascicularis</topic><topic>Macaca fascicularis - virology</topic><topic>Macaques</topic><topic>Medicine and Health Sciences</topic><topic>Microbiology and Parasitology</topic><topic>Model testing</topic><topic>Nasopharynx</topic><topic>Nasopharynx - virology</topic><topic>Normal distribution</topic><topic>Parameter estimation</topic><topic>Physiological aspects</topic><topic>Prophylaxis</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV-2 - drug effects</topic><topic>SARS-CoV-2 - physiology</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Standard deviation</topic><topic>Trachea</topic><topic>Trachea - virology</topic><topic>Upper bounds</topic><topic>Viral diseases</topic><topic>Viral Load</topic><topic>Virology</topic><topic>Virus diseases</topic><topic>Virus Replication</topic><topic>Virus Replication - drug effects</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gonçalves, Antonio</creatorcontrib><creatorcontrib>Maisonnasse, Pauline</creatorcontrib><creatorcontrib>Donati, Flora</creatorcontrib><creatorcontrib>Albert, Mélanie</creatorcontrib><creatorcontrib>Behillil, Sylvie</creatorcontrib><creatorcontrib>Contreras, Vanessa</creatorcontrib><creatorcontrib>Naninck, Thibaut</creatorcontrib><creatorcontrib>Marlin, Romain</creatorcontrib><creatorcontrib>Solas, Caroline</creatorcontrib><creatorcontrib>Pizzorno, Andres</creatorcontrib><creatorcontrib>Lemaitre, Julien</creatorcontrib><creatorcontrib>Kahlaoui, Nidhal</creatorcontrib><creatorcontrib>Terrier, Olivier</creatorcontrib><creatorcontrib>Ho Tsong Fang, Raphael</creatorcontrib><creatorcontrib>Enouf, Vincent</creatorcontrib><creatorcontrib>Dereuddre-Bosquet, Nathalie</creatorcontrib><creatorcontrib>Brisebarre, Angela</creatorcontrib><creatorcontrib>Touret, Franck</creatorcontrib><creatorcontrib>Chapon, Catherine</creatorcontrib><creatorcontrib>Hoen, Bruno</creatorcontrib><creatorcontrib>Lina, Bruno</creatorcontrib><creatorcontrib>Rosa Calatrava, Manuel</creatorcontrib><creatorcontrib>de Lamballerie, Xavier</creatorcontrib><creatorcontrib>Mentré, France</creatorcontrib><creatorcontrib>Le Grand, Roger</creatorcontrib><creatorcontrib>van der Werf, Sylvie</creatorcontrib><creatorcontrib>Guedj, Jérémie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Computing Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Computer Science Collection</collection><collection>Computer Science Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Computing Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Publicly Available Content database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS computational biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gonçalves, Antonio</au><au>Maisonnasse, Pauline</au><au>Donati, Flora</au><au>Albert, Mélanie</au><au>Behillil, Sylvie</au><au>Contreras, Vanessa</au><au>Naninck, Thibaut</au><au>Marlin, Romain</au><au>Solas, Caroline</au><au>Pizzorno, Andres</au><au>Lemaitre, Julien</au><au>Kahlaoui, Nidhal</au><au>Terrier, Olivier</au><au>Ho Tsong Fang, Raphael</au><au>Enouf, Vincent</au><au>Dereuddre-Bosquet, Nathalie</au><au>Brisebarre, Angela</au><au>Touret, Franck</au><au>Chapon, Catherine</au><au>Hoen, Bruno</au><au>Lina, Bruno</au><au>Rosa Calatrava, Manuel</au><au>de Lamballerie, Xavier</au><au>Mentré, France</au><au>Le Grand, Roger</au><au>van der Werf, Sylvie</au><au>Guedj, Jérémie</au><au>Regoes, Roland R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SARS-CoV-2 viral dynamics in non-human primates</atitle><jtitle>PLoS computational biology</jtitle><addtitle>PLoS Comput Biol</addtitle><date>2021-03-17</date><risdate>2021</risdate><volume>17</volume><issue>3</issue><spage>e1008785</spage><epage>e1008785</epage><pages>e1008785-e1008785</pages><issn>1553-7358</issn><issn>1553-734X</issn><eissn>1553-7358</eissn><abstract>Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (&gt;104 virus) and a within-host reproductive basic number of approximately 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly lost with a half-life of 9 hours, with no significant association between cytokine elevation and clearance, leading to a median time to viral clearance of 10 days, consistent with observations in mild human infections. Given these parameter estimates, we predict that a prophylactic treatment blocking 90% of viral production or viral infection could prevent viral growth. In conclusion, our results provide estimates of SARS-CoV-2 viral kinetic parameters in an experimental model of mild infection and they provide means to assess the efficacy of future antiviral treatments.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33730053</pmid><doi>10.1371/JOURNAL.PCBI.1008785</doi><orcidid>https://orcid.org/0000-0002-0943-9648</orcidid><orcidid>https://orcid.org/0000-0002-0555-207X</orcidid><orcidid>https://orcid.org/0000-0002-0918-6804</orcidid><orcidid>https://orcid.org/0000-0001-6239-0110</orcidid><orcidid>https://orcid.org/0000-0002-5534-5482</orcidid><orcidid>https://orcid.org/0000-0002-3210-8468</orcidid><orcidid>https://orcid.org/0000-0003-4784-0819</orcidid><orcidid>https://orcid.org/0000-0002-4928-4484</orcidid><orcidid>https://orcid.org/0000-0002-1520-5020</orcidid><orcidid>https://orcid.org/0000-0002-6261-6412</orcidid><orcidid>https://orcid.org/0000-0001-9393-7684</orcidid><orcidid>https://orcid.org/0000-0002-3826-8729</orcidid><orcidid>https://orcid.org/0000-0002-7045-1275</orcidid><orcidid>https://orcid.org/0000-0002-4734-2249</orcidid><orcidid>https://orcid.org/0000-0001-8932-0171</orcidid><orcidid>https://orcid.org/0000-0001-7895-2720</orcidid><orcidid>https://orcid.org/0000-0002-8759-2429</orcidid><orcidid>https://orcid.org/0000-0003-2862-9751</orcidid><orcidid>https://orcid.org/0000-0002-2322-3392</orcidid><orcidid>https://orcid.org/0000-0001-7609-4742</orcidid><orcidid>https://orcid.org/0000-0003-3070-3017</orcidid><orcidid>https://orcid.org/0000-0002-1148-4456</orcidid><orcidid>https://orcid.org/0000-0001-6682-6313</orcidid><orcidid>https://orcid.org/0000-0002-8959-2123</orcidid><orcidid>https://orcid.org/0000-0002-7559-9527</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1553-7358
ispartof PLoS computational biology, 2021-03, Vol.17 (3), p.e1008785-e1008785
issn 1553-7358
1553-734X
1553-7358
language eng
recordid cdi_plos_journals_2513683896
source PubMed Central; Coronavirus Research Database; ProQuest Publicly Available Content database
subjects Analysis
Animals
Antiviral Agents
Antiviral Agents - pharmacology
Basic Reproduction Number
Biology and Life Sciences
COVID-19
COVID-19 - blood
COVID-19 - prevention & control
COVID-19 - virology
Cytokines
Cytokines - blood
Disease Models, Animal
Disease prevention
Dosage
Dynamic models
Health aspects
Infections
Influenza
Laboratory animals
Life Sciences
Macaca fascicularis
Macaca fascicularis - virology
Macaques
Medicine and Health Sciences
Microbiology and Parasitology
Model testing
Nasopharynx
Nasopharynx - virology
Normal distribution
Parameter estimation
Physiological aspects
Prophylaxis
SARS-CoV-2
SARS-CoV-2 - drug effects
SARS-CoV-2 - physiology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Standard deviation
Trachea
Trachea - virology
Upper bounds
Viral diseases
Viral Load
Virology
Virus diseases
Virus Replication
Virus Replication - drug effects
Viruses
title SARS-CoV-2 viral dynamics in non-human primates
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